US20040234699A1 - Methods of controlling uniformity of substrate temperature and self-contained heating unit and drug-supply unit employing same - Google Patents

Methods of controlling uniformity of substrate temperature and self-contained heating unit and drug-supply unit employing same Download PDF

Info

Publication number
US20040234699A1
US20040234699A1 US10851429 US85142904A US2004234699A1 US 20040234699 A1 US20040234699 A1 US 20040234699A1 US 10851429 US10851429 US 10851429 US 85142904 A US85142904 A US 85142904A US 2004234699 A1 US2004234699 A1 US 2004234699A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
fuel
solid
embodiments
certain
drug
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10851429
Inventor
Ron Hale
Reynaldo Quintana
Krishnamohan Sharma
Dennis Solas
Soonho Song
Pravin Soni
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alexza Pharmaceuticals Inc
Original Assignee
Alexza Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00Sprayers or atomisers specially adapted for therapeutic purposes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A61M11/041Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A61M11/041Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters
    • A61M11/042Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters electrical
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A61M11/041Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters
    • A61M11/047Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters by exothermic chemical reaction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00Inhalators
    • A61M15/06Inhaling appliances shaped like cigars, cigarettes or pipes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01BBOILING; BOILING APPARATUS; EVAPORATION; EVAPORATION APPARATUS
    • B01B1/00Boiling; Boiling apparatus for physical or chemical purposes ; Evaporation in general
    • B01B1/005Evaporation or evaporation apparatus for physical or chemical purposes, e.g. evaporation of liquids for gas phase reactions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B65CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65BMACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
    • B65B29/00Packaging of materials presenting special problems
    • B65B29/10Packaging two or more different substances isolated from one another in the package but capable of being mixed without opening the package, e.g. forming packages containing a resin and hardener isolated by a frangible partition
    • CCHEMISTRY; METALLURGY
    • C06EXPLOSIVES; MATCHES
    • C06BEXPLOSIVES OR THERMIC COMPOSITIONS; MANUFACTURE THEREOF; USE OF SINGLE SUBSTANCES AS EXPLOSIVES
    • C06B33/00Compositions containing particulate metal, alloy, boron, silicon, selenium or tellurium with at least one oxygen supplying material which is either a metal oxide or a salt, organic or inorganic, capable of yielding a metal oxide
    • CCHEMISTRY; METALLURGY
    • C06EXPLOSIVES; MATCHES
    • C06BEXPLOSIVES OR THERMIC COMPOSITIONS; MANUFACTURE THEREOF; USE OF SINGLE SUBSTANCES AS EXPLOSIVES
    • C06B45/00Compositions or products which are defined by structure or arrangement of component of product
    • C06B45/12Compositions or products which are defined by structure or arrangement of component of product having contiguous layers or zones
    • C06B45/14Compositions or products which are defined by structure or arrangement of component of product having contiguous layers or zones a layer or zone containing an inorganic explosive or an inorganic explosive or an inorganic thermic component
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; MISCELLANEOUS COMPOSITIONS; MISCELLANEOUS APPLICATIONS OF MATERIALS
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K5/00Heat-transfer, heat-exchange or heat-storage materials, e.g. refrigerants; Materials for the production of heat or cold by chemical reactions other than by combustion
    • C09K5/16Materials undergoing chemical reactions when used
    • C09K5/18Non-reversible chemical reactions
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F24HEATING; RANGES; VENTILATING
    • F24VCOLLECTION, PRODUCTION OR USE OF HEAT NOT OTHERWISE PROVIDED FOR
    • F24V30/00Apparatus or devices using heat produced by exothermal chemical reactions other than combustion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A61M11/041Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters
    • A61M11/048Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters with a flame, e.g. using a burner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/0015Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors
    • A61M2016/0018Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical
    • A61M2016/0021Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical with a proportional output signal, e.g. from a thermistor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/0027Accessories therefor, e.g. sensors, vibrators, negative pressure pressure meter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/06Solids
    • A61M2202/064Powder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/36General characteristics of the apparatus related to heating or cooling
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/36General characteristics of the apparatus related to heating or cooling
    • A61M2205/364General characteristics of the apparatus related to heating or cooling by chemical reaction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/36General characteristics of the apparatus related to heating or cooling
    • A61M2205/3653General characteristics of the apparatus related to heating or cooling by Joule effect, i.e. electric resistance
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/82Internal energy supply devices
    • A61M2205/8268Fuel storage cells
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F23COMBUSTION APPARATUS; COMBUSTION PROCESSES
    • F23BMETHODS OR APPARATUS FOR COMBUSTION USING ONLY SOLID FUEL
    • F23B2900/00Special features of, or arrangements for combustion apparatus using solid fuels; Combustion processes therefor
    • F23B2900/00003Combustion devices specially adapted for burning metal fuels, e.g. Al or Mg
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F23COMBUSTION APPARATUS; COMBUSTION PROCESSES
    • F23CMETHODS OR APPARATUS FOR COMBUSTION USING FLUID FUEL OR SOLID FUEL SUSPENDED IN  A CARRIER GAS OR AIR 
    • F23C2900/00Special features of, or arrangements for combustion apparatus using fluid fuels or solid fuels suspended in air; Combustion processes therefor
    • F23C2900/99008Unmixed combustion, i.e. without direct mixing of oxygen gas and fuel, but using the oxygen from a metal oxide, e.g. FeO
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02EREDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
    • Y02E20/00Combustion technologies with mitigation potential
    • Y02E20/30Technologies for a more efficient combustion or heat usage
    • Y02E20/34Indirect CO2 mitigation, i.e. by acting on non CO2 directly related matters of the process, e.g. more efficient use of fuels
    • Y02E20/346Unmixed combustion

Abstract

Methods for rapid heating while controlling the uniformity of temperature of a substrate and peak temperatures are disclosed. Heating units, drug supply units and drug delivery articles employing these methods are disclosed. Rapid heating is obtained by use of a solid fuel capable of undergoing an exothermnic metal oxidation reaction disposed within the substrate are disclosed. Drug supply units and drug delivery articles wherein a solid fuel is configured to heat a substrate to a temperature sufficient to rapidly thermally vaporize a drug disposed thereon are also disclosed.

Description

    REFERENCE TO RELATED APPLICATIONS
  • [0001]
    This application is a continuation-in-part and claims priority to U.S. provisional application Ser. No. 60/472,697 entitled “Self-Contained Heating Unit and Drug-Supply Unit Employing Same,” filed May 21, 2003, Hale et al., the entire disclosure of which is hereby incorporated by reference.
  • FIELD
  • [0002]
    This disclosure relates to heating units capable of rapidly heating the substrate to essentially uniform temperature across the surface and to articles and methods employing such heating units.
  • INTRODUCTION
  • [0003]
    Self-contained heat sources are employed in a wide-range of industries, from food industries for heating food and drink, to outdoor recreation industries for providing hand and foot warmers, to medical applications for inhalation devices. Many self-contained heating sources are based on either an exothermic chemical reaction or on ohmic heating. For example, self-heating units that produce heat by an exothermic chemical reaction often have at least two compartments, one for holding a heat-producing composition and one for holding an activating solution. The two compartments are separated by a frangible seal, that when broken allows mixing of the components to initiate an exothermic reaction to generate heat. (see for example U.S. Pat. Nos. 5,628,304; 4,773,389; 6,289,889). This type of non-combustible, self-heating unit is suitable for heating food, drink, or cold toes and fingers, since the heat production is relatively mild.
  • [0004]
    Another common source for self-contained heat is ohmic heating. In ohmic heating a current is passed through an electrically resistive material to generate heat that is transmitted to an adjacent article. This mode of heat production has been employed to vaporize or heat a volatile substance, for example tobacco, for inhalation by a user. Cigarette holders and pipe bowls having an electrical resistance coil to generate heat in order to volatilize tobacco flavors have been described (U.S. Pat. Nos. 2,104,266; 4,922,901; 6,095,143). Heating of drugs other than tobacco by ohmic heating have also been described. For example, WO 94/09842 to Rosen describes applying a drug to an electrically resistive surface and heating the surface to vaporize the drug for inhalation. Ohmic heating has the advantage of facilitating precise control of the energy applied to determine the heat generated. However, in many ohmic heating systems, and in particular for small systems where limited energy is available, such as, for example, when using batteries, there can be a substantial delay on the order of seconds or minutes between the time heating is initiated and maximum temperature is achieved. Moreover, for small devices, such as for example, portable medical devices, where the power source comprises a battery, ohmic heating can be expensive and bulky.
  • [0005]
    Another approach for providing a controlled amount of heat is using electrochemical interactions. Here, components that interact electrochemically after initiation in an exothermic reaction are used to generate heat. Exothermic electrochemical reactions include reactions of a metallic agent and an electrolyte, such as a mixture of magnesium granules and iron particles as the metallic agent, and granular potassium chloride crystals as the electrolyte. In the presence of water, heat is generated by the exothermic hydroxylation of magnesium, where the rate of hydroxylation is accelerated in a controlled manner by the electrochemical interaction between magnesium and iron, which is initiated when the potassium chloride electrolyte dissociates upon contact with the liquid water. Electrochemical interactions have been used in the smoking industry to volatilize tobacco for inhalation (U.S. Pat. Nos. 5,285,798; 4,941,483; 5,593,792).
  • [0006]
    The aforementioned self-heating methods are capable of generating heat sufficient to heat an adjacent article to several hundred degrees Celsius in a period of several minutes. There remains a need in the art for a device capable of rapid heat production, i.e., on the order of seconds and fractions of seconds, capable of heating with essential uniformity an article to within a defined temperature range, and which is suitable for use in articles to be used by people.
  • SUMMARY
  • [0007]
    Certain embodiment disclose methods of controlling uniformity of temperature and peak temperature of a substrate surface by coating a thin layer of a selected mass of a solid fuel on a surface of the substrate.
  • [0008]
    Certain embodiments include heating units comprising an enclosure and a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure.
  • [0009]
    Certain embodiments include drug supply units comprising an enclosure having at least one substrate having an exterior surface and an interior surface, a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure, and a drug disposed on a portion of the exterior surface of the substrate.
  • [0010]
    Certain embodiments include drug delivery devices comprising a housing defining an airway, a heating unit comprising an enclosure having at least one substrate having an exterior surface and an interior surface, and a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure, a drug disposed on a portion of the exterior surface of the substrate, wherein the portion of the exterior surface comprising the drug is configured to be disposed within the airway, and an igniter configured to ignite the solid fuel.
  • [0011]
    Certain embodiments include methods of producing an aerosol of a drug and of treating a disease in a patient using such heating units, drug supply units, and drug delivery devices.
  • [0012]
    It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of certain embodiments, as claimed.
  • DESCRIPTION OF THE DRAWINGS
  • [0013]
    [0013]FIG. 1A is a cross-sectional illustration of a heating unit according to certain embodiments.
  • [0014]
    [0014]FIG. 1B is a perspective illustration of a heating unit according to certain embodiments.
  • [0015]
    [0015]FIG. 2A is a cross-sectional illustration of a heating unit having a cylindrical geometry according to certain embodiments.
  • [0016]
    [0016]FIG. 2B is a perspective illustration of a heating unit having a cylindrical geometry according to certain embodiments.
  • [0017]
    [0017]FIG. 2C is a cross-sectional illustration of a cylindrical heating unit similar to the heating unit of FIGS. 2A-2B but having a modified igniter design according to certain embodiments.
  • [0018]
    [0018]FIG. 2D is a cross-sectional illustration of a cylindrically-shaped heating unit that includes a thermal shunt according to certain embodiments.
  • [0019]
    [0019]FIG. 3 is a schematic cross-sectional illustration of a chemical heating unit having two pressure transducers for measuring the internal pressure during and after ignition of the solid fuel according to certain embodiments.
  • [0020]
    [0020]FIGS. 4A-4F are thermal images of a cylindrically-shaped heating unit measured using an infrared thermal imaging camera at post-ignition times of 100 milliseconds (FIG. 4A), 200 milliseconds (FIG. 4B), 300 milliseconds (FIG. 4C), 400 milliseconds (FIG. 4D), 500 milliseconds (FIG. 4E), and 600 milliseconds (FIG. 4F) according to certain embodiments.
  • [0021]
    [0021]FIGS. 5A-5B are thermal images showing the temperature uniformity of the exterior substrate surface expanse 400 milliseconds after ignition of two cylindrically-shaped heating units according to certain embodiments.
  • [0022]
    [0022]FIGS. 6A-6C show schematic illustrations of the generation of drug vapor from a drug supply unit carrying a film of drug on the exterior substrate surface (FIG. 6A); ignition of the heating unit (FIG. 6B); and generation of a wave of heat effective to vaporize the drug film (FIG. 6C) according to certain embodiments.
  • [0023]
    [0023]FIGS. 7A-7E are high speed photographs showing the generation of thermal vapor from a drug supply unit as a function of time following ignition of the solid fuel according to certain embodiments.
  • [0024]
    [0024]FIG. 8 shows a drug delivery device containing a heating unit as part of an inhalation drug delivery device for delivery of an aerosol comprising a drug according to certain embodiments.
  • [0025]
    [0025]FIGS. 9A-9C show drug supply units for use in drug delivery devices designed for delivering multiple drug doses according to certain embodiments.
  • [0026]
    [0026]FIGS. 10A-10B show illustrations of a perspective view (FIG. 10A) and an assembly view (FIG. 10B) of a thin film drug supply unit according to certain embodiments;
  • [0027]
    [0027]FIGS. 11A-11B show cross-sectional illustrations of thin film drug supply units comprising multiple doses according to certain embodiments.
  • [0028]
    [0028]FIG. 12 shows a relationship between the mass of a solid fuel coating and the peak temperature of the exterior surface of a substrate according to certain embodiments.
  • [0029]
    [0029]FIG. 13A is an illustration of a cross-sectional view of a heating unit having an impulse absorbing material disposed within the unit.
  • [0030]
    [0030]FIG. 13B is an illustration of a cross-sectional view of a cylindrical heating unit having an impulse absorbing material disposed within the unit.
  • [0031]
    [0031]FIG. 13C is an illustration of a cross-sectional view of a heating unit having an impulse absorbing material and an additional pressure reducing element disposed with the enclosure.
  • [0032]
    [0032]FIG. 14 shows the measured pressure within heating units comprising glass fiber mats following ignition of the solid fuel.
  • [0033]
    [0033]FIG. 15 shows the temperature at various positions within a heating unit following ignition of the solid fuel.
  • [0034]
    [0034]FIG. 16 is a schematic illustration of an igniter comprising an initiator composition disposed on an electrically resistive heating element.
  • [0035]
    [0035]FIG. 17 shows peak internal pressure within sealed heating units following ignition of a thin film layer of solid fuel comprising a metal reducing agent and a metal-containing oxidizer.
  • [0036]
    [0036]FIG. 18 shows the relationship of the yield and purity of an aerosol comprising a specific pharmaceutical compound using different substrate temperatures obtained from different masses of solid fuel for various embodiments.
  • [0037]
    [0037]FIG. 19 shows a temperature profile of a heating unit substrate following ignition of the solid fuel.
  • DESCRIPTION OF VARIOUS EMBODIMENTS
  • [0038]
    Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.”
  • [0039]
    In this application, the use of the singular includes the plural unless specifically stated otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, the use of the term “including,” as well as other forms, such as “includes” and “included,” is not limiting. Also, terms such as “element” or “component” encompass both elements and components comprising one unit and elements and components that comprise more than one subunit unless specifically stated otherwise.
  • COATED SUBSTRATES AND TEMPERATURE CONTROL
  • [0040]
    [0040]FIG. 1A shows an example of a substrate 12, such as those used in this invention. The substrate can be formed from a thermally-conductive material. Thermally-conductive materials are well known, and typically include, but are not limited to, metals, such as aluminum, iron, copper, stainless steel, and the like, alloys, ceramics, and filled polymers. The substrate can be formed from one or more such materials and in certain embodiments, can have a multilayer structure. For example, the substrate can comprise one or more films and/or coatings and/or multiple sheets or layers of materials. In certain embodiments, portions of the substrate can be formed from multiple sections. In certain embodiments, the multiple sections forming the substrate of the heating unit can have different thermal properties. A substrate can be of any appropriate geometry, the rectangular configuration shown in FIG. 1A is merely exemplary. A substrate can also have any appropriate thickness and the thickness of the substrate can be different in certain regions. Substrate 12, as shown in FIG. 1A, has an interior surface 14 and an exterior surface 16. Heat can be conducted from interior surface 14 to exterior surface 16. An article or object placed adjacent or in contact with exterior surface 16 can receive the conducted heat to achieve a desired action, such as warming or heating a solid or fluid object, effecting a further reaction, or causing a phase change. In certain embodiments, the conducted heat can effect a phase transition in a compound in contact, directly or indirectly, with exterior surface 16.
  • [0041]
    Solid fuels can be used to heat the substrates rapidly. The energy released during an exothermic reaction using solid fuels can be used to provide the temperature rise required to heat directly or indirectly a material adjacent to the exterior surface. In certain embodiments, the substrate 12 has an expanse of a solid fuel 20, in direct contact with or adjoining interior surface 14.
  • [0042]
    The solid fuel can be any appropriate shape and have any appropriate dimensions. For example, as shown in FIG. 1A, solid fuel 20 can comprise a surface expanse 26 and side expanses 28, 30. As shown in FIG. 1B, heating unit 40 comprises a substrate 42 having an exterior surface 44 and an interior surface 46. In certain embodiments, solid fuel 48, is in the shape of a hollow rod extending the length of substrate 42 and exhibiting a diameter less than that of interior surface 46. It can be appreciated that a finned or ribbed exterior surface can provide a high surface area that can be useful to facilitate heat transfer from the solid fuel to an article or composition in contact with the surface.
  • [0043]
    The components of the solid fuel can react in an exothermic reaction to produce heat. For example, the solid fuel can react in an exothermic oxidation-reduction reaction or an intermetallic alloying reaction. An oxidation-reduction reaction refers to a chemical reaction in which one compound gains electrons and another compound loses electrons. The compound that gains electrons is referred to as an oxidizing agent, and the compound that loses electrons is referred to as a reducing agent. An example of an oxidation-reduction reaction is a chemical reaction of a compound with molecular oxygen (O2) or an oxygen-containing compound that adds one or more oxygen atoms to the compound being oxidized. During the oxidation-reduction reaction, the molecular oxygen or the oxygen-containing compound is reduced by the compound being oxidized. The compound providing oxygen acts as the oxidizer or oxidizing agent. The compound being oxidized acts as the reducing agent. Oxidation-reduction reactions can be exothermic, meaning that the reactions generate heat. An example of an exothermic oxidation-reduction reaction is the thermite reaction of a metal with a metal oxidizing agent. In certain embodiments, a solid fuel can comprise a metal reducing agent and an oxidizing agent, such as for example, a metal-containing oxidizing agent.
  • [0044]
    In certain embodiments, the metal reducing agent and the oxidizing agent can be in the form of a powder. The term “powder” refers to powders, particles, prills, flakes, and any other particulate that exhibits an appropriate size and/or surface area to sustain self-propagating ignition. For example, in certain embodiments, the powder can comprise particles exhibiting an average diameter ranging from 0.1 μm to 200 μm.
  • [0045]
    In certain embodiments, a metal reducing agent can include, but is not limited to molybdenum, magnesium, calcium, strontium, barium, boron, titanium, zirconium, vanadium, niobium, tantalum, chromium, tungsten, manganese, iron, cobalt, nickel, copper, zinc, cadmium, tin, antimony, bismuth, aluminum, and silicon. In certain embodiments, a metal reducing agent can include aluminum, zirconium, and titanium. In certain embodiments, a metal reducing agent can comprise more than one metal reducing agent.
  • [0046]
    In certain embodiments, an oxidizing agent can comprise oxygen, an oxygen based gas, and/or a solid oxidizing agent. In certain embodiments, an oxidizing agent can comprise a metal-containing oxidizing agent. In certain embodiments, a metal-containing oxidizing agent includes, but is not limited to, perchlorates and transition metal oxides. Perchlorates can include perchlorates of alkali metals or alkaline earth metals, such as, but not limited to, potassium perchlorate (KClO4), potassium chlorate (KClO3), lithium perchlorate (LiClO4), sodium perchlorate (NaClO4), and magnesium perchlorate [Mg(ClO4)2]. In certain embodiments, transition metal oxides that function as oxidizing agents include, but are not limited to, oxides of molybdenum, such as MoO3, iron, such as Fe2O3, vanadium (V2O5), chromium (CrO3, Cr2O3), manganese (MnO2), cobalt (Co3O4), silver (Ag2O), copper (CuO), tungsten (WO3), magnesium (MgO), and niobium (Nb2O5). In certain embodiments, the metal-containing oxidizing agent can include more than one metal-containing oxidizing agent.
  • [0047]
    In certain embodiments, the metal reducing agent forming the solid fuel can be selected from zirconium and aluminum, and the metal-containing oxidizing agent can be selected from MoO3 and Fe2O3.
  • [0048]
    The ratio of metal reducing agent to metal-containing oxidizing agent can be selected to determine the ignition temperature and the burn characteristics of the solid fuel. An exemplary chemical fuel can comprise 75% zirconium and 25% MoO3, percentage based on weight. In certain embodiments, the amount of metal reducing agent can range from 60% by weight to 90% by weight of the total dry weight of the solid fuel. In certain embodiments, the amount of metal-containing oxidizing agent can range from 10% by weight to 40% by weight of the total dry weight of the solid fuel. In certain embodiments, the amount of oxidizing agent in the solid fuel can be related to the molar amount of the oxidizers at or near the eutectic point for the fuel composition. In certain embodiments, the oxidizing agent can be the major component and in others the metal reducing agent can be the major component. Those of skill in the art are able to determine the appropriate amount of each component based on the stoichiometry of the chemical reaction and/or by routine experimentation. Also as known in the art, the particle size of the metal and the metal-containing oxidizer can be varied to determine the burn rate, with smaller particle sizes selected for a faster burn (see, for example, U.S. Pat. No. 5,603,350).
  • [0049]
    In certain embodiments, a solid fuel can comprise additive materials to facilitate, for example, processing and/or to determine the thermal and temporal characteristics of a heating unit during and following ignition of the solid fuel. An additive material can be reactive or inert. An inert additive material will not react or will react to a minimal extent during ignition and burning of the solid fuel. The additive can comprise inorganic or organic materials.
  • [0050]
    In certain applications, particularly, where it is desirous to produce a minimal amount of gas, such as for example, in a sealed heating unit, the additive material can be inorganic materials. These inorganic materials can function as binders, adhesives, gelling agents, thixotropic agents, and/or surfactants. Examples of gelling agents include, but are not limited to, clays such as Laponite®, Montmorillonite, Cloisite®, metal alkoxides, such as those represented by the formula R—Si(OR)nand M(OR)n where n can be 3 or 4, and M can be Ti, Zr, Al, B or other metals, and collidal particles based on transition metal hydroxides or oxides. Examples of binding agents include, but are not limited to, soluble silicates such as Na- or K-silicates, aluminum silicates, metal alkoxides, inorganic polyanions, inorganic polycations, and inorganic sol-gel materials, such as alumina or silica-based sols.
  • [0051]
    In certain embodiments it can be useful that the solid fuel adhere to the surface of the substrate and that the constituents of the solid fuel adhere to each other, and maintain physical integrity. In certain embodiments, it can be useful that the solid fuel remain adhered to the substrate surface and maintain physical integrity during processing, storage, and use during which time the solid fuel coating can be exposed to a variety of mechanical and environmental conditions. As discussed above, several additives, such as those disclosed herein, can be incorporated into the solid fuel to impart adhesion and physical robustness to the solid fuel coating.
  • [0052]
    In certain embodiments, the solid fuel comprises Laponite®, and in particular Laponite® RDS, as an inert additive material. Laponite® is a synthetic layered silicate, and in particular a magnesium phyllosilicate, with a structure resembling that of the natural clay mineral hectorite (Na0.4Mg2.7Li0.3Si4O10(OH)2). Laponite® RD is a commercial grade material which, when added to water, rapidly disperses to form a gel when hydrated (Southern Clay Products, Gonzales, Tex.). Laponite® RD has the following chemical analysis in weight percent: 59.5% SiO2: 27.5% MgO: 0.8% Li2O: 2.8% Na2O. Laponite® RDS (Southern Clay Products, Gonzales, Tex.) is a commercially available sol-forming grade of Laponite® modified with a polyphosphate dispersing agent, or peptizer, to delay rheological activity until the Laponite® RDS is added as a dispersion into a formulation. A sol refers to a colloid having a continuous liquid phase in which solid is suspended in a liquid. Laponite® RDS has the following chemical analysis in weight percent: 54.5% SiO2:26% MgO: 0.8% Li2O: 5.6% Na2O: 4.1% P2O5, In the presence of electrolytes, Laponites® can act as gelling and thixotropic agents. Thixotropy refers to the property of a material to exhibit decreased viscosity under shear.
  • [0053]
    When incorporated into a solid fuel composition comprising a metal reducing agent and a metal-containing oxidizing agent, such as any of those disclosed herein, in addition to imparting gelling and thixotropic properties, Laponite® RDS can also act as binder.
  • [0054]
    An example of the preparation of a solid fuel comprising Laponite® RDS and the application of the solid fuel to a metal foil substrate are described in Example 1.
  • [0055]
    Other useful additive materials include glass beads, diatomaceous earth, nitrocellulose, polyvinylalcohol, and other polymers that may function as binders. In certain embodiments, the solid fuel can comprise more than one additive material. The components of the solid fuel comprising the metal, oxidizing agent and/or additive material and/or any appropriate aqueous- or organic-soluble binder, can be mixed by any appropriate physical or mechanical method to achieve a useful level of dispersion and/or homogeneity. In certain embodiments, the solid fuel can be degassed.
  • [0056]
    In addition, to the enhanced binding properties of the solid fuels with additive, other advantages of using inorganic additives include stability of the additive up to very high temperatures and lack of, or minimal release of, any toxic gases by the additive. In an enclosed system, this lack of additional gas production from the inorganic additive also reduces or minimizes the possibility of rupture of the enclosed heating unit.
  • [0057]
    Tables 1A-1E summarize certain embodiments of solid fuel compositions including the additives used. The weight ratio of the components comprising certain solid fuel compositions are provided.
    TABLE 1A
    Embodiments of Solid Fuel Compositions (wt %)
    Component Fuel #1 Fuel #2 Fuel #3 Fuel #4 Fuel #5 Fuel #6 Fuel #7 Fuel #8
    Zirconium (Zr) 70-90 20-40 20-30
    Titanium (Ti) 70-92 60-80
    Iron (Fe) 70-90
    Magnesium (Mg) 20-40 40-60
    Boron (B) 20-40
    Potassium perchlorate 10-30  8-30 10-30
    (KClO4)
    Lead Oxide (PbO) 40-60
    Tungsten Oxide (WO3) 60-80
    Barium Chromate 70-80
    (BaCrO4)
    Teflon 60-80
  • [0058]
    [0058]
    TABLE 1B
    Embodiments of Solid Fuel Compositions (wt %)
    Component Fuel #9 Fuel #10 Fuel #11 Fuel #12 Fuel #13 Fuel #14 Fuel #15 Fuel #16
    Zirconium (Zr) 21 10-50
    Titanium (Ti) 60-80 70-92  82 55 33-81
    Iron (Fe) 0-84
    Aluminum (Al) 20-40 20
    Nickel (Ni) 60-80
    Boron (B) 25
    Potassium perchlorate 8-30  9-17 50
    (KClO4)
    Potassium chlorate (KClO3) 18
    Tungsten Oxide (WO3) 20-40
    Barium Chromate (BaCrO4) 64
    Zirconium Carbide (ZrC) 50
    Diatomaceous Earth 15
  • [0059]
    [0059]
    TABLE 1C
    Embodiments of Solid Fuel Compositions (wt %)
    Fuel Fuel Fuel Fuel Fuel Fuel Fuel Fuel
    Component #17 #18 #19 #20 #21 #22 #23 #24
    Zirconium (Zr) 50-65  50-72 30-80 65 55-70
    Titanium (Ti) 20-70
    Boron (B) 15
    Potassium Perchlorate 52.5
    (KClO4)
    Molybdenum Oxide 0-50 30-80 20-70 25-33
    (MoO3)
    Iron Oxide 0-50 85 28-50 25
    (Fe2O3)
    Zirconium Hydride 47.5
    (ZrH2)
    Diatomaceous Earth balance 10  5-12
  • [0060]
    [0060]
    TABLE 1D
    Embodiments of Solid Fuel Compositions (wt %)
    Fuel Fuel Fuel Fuel Fuel Fuel Fuel Fuel Fuel
    Component #25 #26 #27 #28 #29 #30 #31 #32 #33
    Zirconium (Zr) 35-50 63-69 70 34 66.5-69   66.5-74.6   54-66.5 69 69
    Titanium (Ti) 20-35
    Molybdenum Oxide 30   27-29.5 30 54 28.5-29   24.87-29   28.5-34   29.85 29.85
    (MoO3)
    Nitrocellulose excess 0.53-4.5  0.5 0.5
    Cab-O-Sil   4-7.5
    Glass Fber 12 0.65
    Glass Microsphere 0.65
    Polyvinyl Alcohol 2.5-4.5
    High Vacuum Grease  5-12
  • [0061]
    [0061]
    TABLE 1E
    Embodiments of Solid Fuel Compositions (wt %)
    Fuel Fuel Fuel Fuel Fuel Fuel Fuel Fuel Fuel Fuel
    Component #34 #35 #36 #37 #38 #39 #40 #41 #42 #43
    Zirconium (Zr) 66.5-69 69.65 69.7-74.6 49-59.5 47-70 40 20
    Magnesium (Mg) 40
    Aluminum (Al) 36-70 50-55 30
    Silicon (Si) 30
    Potassium 0-3
    chlorate (KClO3)
    Bismuth Oxide 50
    (Bi2O3)
    Molybdenum 28.5-29 29.85 24.9-29.8 21-25.5 30-64 40 23.1-38   45-50 30
    Oxide (MoO3)
    Diatomaceous 19-25   balance
    Earth or excess
    Nitrocellulose 0.5 0.4-2   1
    Glass Beads 20
    Carboxymethyl excess
    cellulose
    Polyvinyl alcohol 0.5
    40% Aqueous   2-5
    SiO2
    Viton-A 0.5
  • [0062]
    While the use of additives in the solid fuel can improve the binding properties of the solid fuel, it also can improve the ease of use and manufacturability of substrates coated with such fuel. In particular, use of additives can make it possible to use wet-coating techniques, such as, for example, but not limitation, dip coating, spray coating, roller coating, gravure coating, reverse roll coating, gap coating, metering rod coating, slot die coating, curtain coating, and air knife coating, as means for deposition of a fuel powder on a substrate surface, such as, for example, either inside, or on, a cylindrical type surface such as the internal surface of the substrate in FIG. 1B, or on a flat surface such as a foil as is shown in FIG. 10A.
  • [0063]
    The use of solid fuel slurries with additives for coating a substrate can provide for better mixing of the materials, enhanced adherence properties, and more control over the even disbursement of the solid fuel on a surface. While preparing a physical mixture of solid fuel powders as an essentially homogeneous layer around the walls of a cylindrical device can be done, it is problematic, especially if the materials used have differences in densities, particle sizes, shapes, surface volume ratios, and lack chemically attractive surface-surface interactions. (Essentially homogeneous is defined, for purposes herein, as essentially uniform; and when applied to a mixture of two or more components, it refers to a basically uniform distribution of the various different particles throughout the mixture. This is in contrast to a heterogeneous mixture of components where various components tend to aggregate and there is settling out of the higher density particles.) Use of a core for dispersing mixtures of fuel powders to an interior surface of a substrate, allows one to control the gap or layer thickness of the solid fuel layer; however, it does not prevent other problems such as segregation of the particles in the mixture. Inadequate homogeneity as to the fuel mixture itself, due to ineffective mixing can result in inconsistent heating of the exterior surface of the substrate. Mixing can be facilitated and even automated when done as a slurry as opposed to a dry powder.
  • [0064]
    Additionally, lack of homogeneity as to the fuel thickness on, or in, contact with an interior surface of a substrate can also result in inconsistent heating of the exterior surface of a substrate. Coating adherence and ease of application can be enhanced by the use of slurries with additives.
  • [0065]
    In certain embodiments, the solid fuel is disposed on a substrate as a coating or thin layer, wherein the thickness of the thin layer of solid fuel can range, for example, from 0.001 inches to 0.030 inches by use of wet coating
  • [0066]
    Substrates such as, for example, substrates 510 shown in FIG. 10A, can be coated to a nearly homogeneous thickness to form a thin coating or a thin layer of solid fuel 512 on the interior region of the substrate corresponding to the exterior surface on which the drug 514 is disposed. The thickness of the substrate, its thermal conductivity, its heat capacity, the thickness of the thin layer of solid fuel 512, and the composition of solid fuel 512 can determine the maximum temperature (peak temperature) as well as the temporal and spatial dynamics of the temperature profile produced by the burning of the solid fuel.
  • [0067]
    Studies using thin solid fuel layers having a thickness ranging from 0.001 inches to 0.005 inches demonstrate that the maximum temperature reached by a thin film substrate on which the solid fuel is disposed can be linear with the mass of solid fuel applied. For example, as shown in FIG. 12 for several different solid fuel compositions, for a 0.001 inch to 0.003 inch thick layer of Zr/MoO3 solid fuel having a mass ranging from 0.13 g to 0.25 g, the maximum temperature reached by the substrate during burn is linear. Other studies with solid fuel layers having a mass ranging from 0.12 g to 0.24 g demonstrate linearity over a temperature ranging from 375° C. to 625° C. It will be appreciated that one skilled in the art can establish similar relationships for other solid fuel compositions and configurations. Such studies demonstrate that the temperature reached by the substrate when the solid fuel is burned can be established by controlling the amount of solid fuel applied to the substrate.
  • [0068]
    Measurements of the substrate surface temperature after firing demonstrate that thin coatings or layers of a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent can produce uniformity of temperature on the exterior surface of the substrate. Uniformity of temperature is defined herein to exist when the temperature in degrees Celsius of the exterior surface of the substrate, corresponding to the fuel coated area of the interior surface of the substrate, is within a standard deviation of 50° C. from the average surface temperature obtained, as measured within 100 milliseconds after completion of propagation of the ignited fuel flame front. A temperature profile of a substrate forming a heating unit substantially as shown in FIGS. 10A and 10B and described in Example 9 following ignition of the solid fuel is shown in FIG. 19. FIG. 19 shows the average surface temperature at various positions across two dimensions of a 1.3 inch×1.3 inch substrate 0.25 seconds following ignition of a 0.00163 inch thick coating of solid fuel. The average surface temperature of the effective heated area was about 400° C.
  • [0069]
    In certain applications, such as for example, vaporization of a drug off the substrate of a heating unit, uniformity of heating of the substrate is critical as it facilitates the production of an aerosol comprising a high purity drug or pharmaceutical composition and maximizes the yield of drug initially deposited on the substrate forming an aerosol.
  • HEATING UNITS
  • [0070]
    An embodiment of a heating unit is shown in FIG. 1A. Heating unit 10 can comprise a substrate 12 with a thin layer or coating of solid fuel 20 in contact with the interior surface 14 of substrate 12. Solid fuel can be ignited to generate a self-sustaining oxidation-reduction reaction. Once a portion of the solid fuel is ignited, the heat generated by the oxidation-reduction reaction can ignite adjacent unburned fuel until all of the fuel is consumed in the process of the chemical reaction. The exothermic oxidation-reduction reaction can be initiated by the application of energy to at least a portion of the solid fuel. Energy absorbed by the solid fuel or by an element in contact with the solid fuel can be converted to heat. When the solid fuel becomes heated to a temperature above the auto-ignition temperature of the reactants, e.g. the minimum temperature required to initiate or cause self-sustaining combustion in the absence of a combustion source or flame, the oxidation-reduction reaction will initiate, igniting the solid fuel in a self-sustaining reaction until the fuel is consumed.
  • [0071]
    Energy can be applied to ignite the solid fuel using a number of methods. For example, a resistive heating element can be positioned in thermal contact with the solid fuel, which when a current is applied, can heat the solid fuel to the auto-ignition temperature. An electromagnetic radiation source can be directed at the solid fuel, which when absorbed, can heat the solid fuel to its auto-ignition temperature. An electromagnetic source can include lasers, diodes, flashlamps and microwave sources. RF or induction heating can heat the solid fuel source by applying an alternating RF field that can be absorbed by materials having high magnetic permeability, either within the solid fuel, or in thermal contact with the solid fuel. The source of energy can be focused onto the absorbing material to increase the energy density to produce a higher local temperature and thereby facilitate ignition. In certain embodiments, the solid fuel can be ignited by percussive forces.
  • [0072]
    The auto-ignition temperature of a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent as disclosed herein can range of 400° C. to 500° C. While such high auto-ignition temperatures facilitate safe processing and safe use of the solid fuel under many use conditions, for example, as a portable medical device, for the same reasons, to achieve such high temperatures, a large amount of energy must be applied to the solid fuel to initiate the self-sustaining reaction. Furthermore, the thermal mass represented by the solid fuel can require that an impractically high temperature be applied to raise the temperature of the solid fuel above the auto-ignition temperature. As heat is being applied to the solid fuel and/or a support on which the solid fuel is disposed, heat is also being conducted away. Directly heating a solid fuel can require a substantial amount of power due to the thermal mass of the solid fuel and support.
  • [0073]
    As is well known in the art, for example, in the pyrotechnic industry, sparks can be used to safely and efficiently ignite fuel compositions. Sparks refer to an electrical breakdown of a dielectric medium or the ejection of burning particles. In the first sense, an electrical breakdown can be produced, for example, between separated electrodes to which a voltage is applied. Sparks can also be produced by ionizing compounds in an intense laser radiation field. Examples of burning particles include those produced by friction and break sparks produced by intermittent electrical current. Sparks of sufficient energy incident on a solid fuel can initiate the self-sustaining oxidation-reduction reaction.
  • [0074]
    When sufficiently heated, the exothermic oxidation-reduction reaction of the solid fuel can produce sparks, as well as radiation energy. Thus, in certain embodiments, reliable, reproducible and controlled ignition of the solid fuel can be facilitated by the use of an initiator composition capable of reacting in an exothermic oxidation-reduction reaction. The initiator composition can comprise the same or similar reactants as those comprising the solid fuel. In certain embodiments, the initiator composition can be formulated to maximize the production of sparks having sufficient energy to ignite a solid fuel. Sparks ejected from an initiator composition can impinge upon the surface of the solid fuel, causing the solid fuel to ignite in a self-sustaining exothermic oxidation-reduction reaction. The igniter can comprise a physically small, thermally isolated heating element on which is applied a small amount of an initiator composition capable of producing sparks or the initiator composition can be placed directly on the fuel itself and ignited by a variety of means, including, for example, optical or percussive.
  • [0075]
    As shown in FIG. 1A, heating unit 10 can include an initiator composition 50 which can ignite a portion of solid fuel 20. In certain embodiments, as shown in FIG. 1A, initiator composition 50 can be positioned proximate to the center region 54 of solid fuel 20. Initiator composition 50 can be positioned at other regions of solid fuel 20, such as toward the edges. In certain embodiments, a heating unit can comprise more than one initiator composition where the more than one initiator composition 50 can be positioned on the same or different side of solid fuel 20. In certain embodiments, initiator composition 50 can be mounted in a retaining member 56 that is integrally formed with substrate 12 and/or secured within a suitably sized opening in substrate 12. Retaining member 56 and substrate 12 can be sealed to prevent release outside heating unit 10 of reactants and reaction products produced during ignition and burning of solid fuel 20. In certain embodiments, electrical leads 58 a, 58 b in electrical contact with initiator composition 50 can extend from retaining member 56 for electrical connection to a mechanism configured to activate (not shown) initiator composition 50.
  • [0076]
    Initiator compositions capable of producing sparks upon exposure to heat, force, or a spark are known, for example, in the pyrotechnic field and the photoflash industry. In certain embodiments, an initiator composition can comprise at least one metal, such as those described herein, and at least one oxidizing agent, such as, for example, a chlorate or perchlorate of an alkali metal or an alkaline earth metal or metal oxide and others disclosed herein. In certain embodiments, an initiator composition can include at least one binder and/or additive material such as a gelling agent and/or binder. Examples of additive materials including gelling agents and/or binders are disclosed herein. In certain embodiments, additive materials can be useful in determining certain processing, ignition, and/or burn characteristics of the initiator composition.
  • [0077]
    [0077]FIG. 2A shows a longitudinal cross-sectional illustration of an embodiment of a heating unit. FIG. 2B shows a corresponding perspective illustration of an embodiment illustrating the unassembled individual components shown in FIG. 2A. As shown in FIG. 2A, heating unit 60 can include a substrate 62 that is generally cylindrical in shape and terminates at one end in a tapered nose portion 64 and at the other end in an open receptacle 66. Substrate 62 has interior and exterior surfaces 68, 70, respectively, which define an inner region 72. An inner backing member 74 can be cylindrical in shape and can be located within inner region 72. The opposing ends 76, 78 of backing member 74 can be open. In certain embodiments, backing member 74 can comprise a heat-conducting or heat-absorbing material, depending on the desired thermal and temporal dynamics of the heating unit. When constructed of a heat-absorbing material, backing member 74 can reduce the maximum temperature reached by substrate 62 after ignition of the solid fuel 80.
  • [0078]
    In certain embodiments, solid fuel 80 comprising, for example, any of the solid fuels described herein, can be confined between substrate 62 and backing member 74 or can fill inner region 72. Solid fuel 80 can adjoin interior surface 68 of substrate 62.
  • [0079]
    In certain embodiments, initiator composition 82 can be positioned in open receptacle 66 of substrate 62, and can be configured to ignite solid fuel 80. In certain embodiments, a retaining member 84 can be located in open receptacle 66 and can be secured in place using any suitable mechanism, such as for example, bonding or welding. Retaining member 84 and substrate 62 can be sealed to prevent release of the reactants or reaction products produced during ignition and burn of initiator composition 82 and solid fuel 80. Retaining member 84 can include a recess 86 in the surface facing inner region 72. Recess 86 can retain initiator composition 82. In certain embodiments, an electrical stimulus can be applied directly to initiator composition 82 via leads 88, 90 connected to the positive and negative termini of a power source, such as a battery (not shown). Leads 88, 90 can be connected to an electrically resistive heating element placed in physical contact with the initiator composition 82 (not shown). In certain embodiments, leads 88, 90 can be coated with the initiator composition 82.
  • [0080]
    Referring to FIG. 2A, application of a stimulus to initiator composition 82 can result in the generation of sparks that can be directed from open end 78 of backing member 74 toward end 76. Sparks directed toward end 76 can contact solid fuel 80, causing solid fuel 80 to ignite. Ignition of solid fuel 80 can produce a self-propagating wave of ignited solid fuel 80, the wave traveling from open end 78 toward nose portion 64 and back toward retaining member 84 held within receptacle end 66 of substrate 62. The self-propagating wave of ignited solid fuel 80 can generate heat that can be conducted from interior surface 68 to exterior surface 70 of substrate 62.
  • [0081]
    An embodiment of a heating unit is illustrated in FIG. 2C. As shown in FIG. 2C, heating unit 60 can comprise a first initiator composition 82 disposed in recess 86 in retaining member 84 and a second initiator composition 94 disposed in open end 76 of backing member 74. Backing member 74, located within inner region 72, defines an open region 96. Solid fuel 80 is disposed within the inner region between substrate 62 and backing member 74. In certain embodiments, sparks generated upon application of an electrical stimulus to first initiator composition 82, through leads 88, 90, can be directed through open region 96 toward second initiator composition 94, causing second initiator composition 94 to ignite and generate sparks. Sparks generated by second initiator composition 94 can then ignite solid fuel 80, with ignition initially occurring toward the nose portion of substrate 62 and traveling in a self-propagating wave of ignition to the opposing end.
  • [0082]
    In certain embodiments, the igniter can comprise a support and an initiator composition disposed on the support. In certain embodiments, the support can be thermally isolated to minimize the potential for heat loss. In this way, dissipation of energy applied to the combination of assembly and support can be minimized, thereby reducing the power requirements of the energy source, and facilitating the use of physically smaller and less expensive heat sources. In certain applications, for example, with battery powered portable medical devices, such considerations can be particularly useful. In certain embodiments, it can be useful that the energy source be a small low cost battery, such as a 1.5 V alkaline battery. In certain embodiments, the initiator composition can comprise a metal reducing agent and metal-containing oxidizing agent.
  • [0083]
    In certain embodiments, a metal reducing agent can include, but is not limited to molybdenum, magnesium, calcium, strontium, barium, boron, titanium, zirconium, vanadium, niobium, tantalum, chromium, tungsten, manganese, iron, cobalt, nickel, copper, zinc, cadmium, tin, antimony, bismuth, aluminum, and silicon. In certain embodiments, a metal reducing agent can include aluminum, zirconium, and titanium. In certain embodiments, a metal reducing agent can comprise more than one metal reducing agent. In certain embodiments, an oxidizing agent can comprise oxygen, an oxygen based gas, and/or a solid oxidizing agent. In certain embodiments, an oxidizing agent can comprise a metal-containing oxidizing agent. In certain embodiments, a metal-containing oxidizing agent includes, but is not limited to, perchlorates and transition metal oxides. Perchlorates can include perchlorates of alkali metals or alkaline earth metals, such as but not limited to, potassium perchlorate (KClO4), potassium chlorate (KClO3), lithium perchlorate (LiClO4), sodium perchlorate (NaClO4), and magnesium perchlorate [Mg(ClO4)2]. In certain embodiments, transition metal oxides that function as oxidizing agents include, but are not limited to, oxides of molybdenum, such as MoO3, iron, such as Fe2O3, vanadium (V2O5), chromium (CrO3, Cr2O3), manganese (MnO2), cobalt (Co3O4), silver (Ag2O), copper (CuO), tungsten (WO3), magnesium (MgO), and niobium (Nb2O5). In certain embodiments, the metal-containing oxidizing agent can include more than one metal-containing oxidizing agent.
  • [0084]
    The ratio of metal reducing agent to metal-containing oxidizing agent can be selected to determine the appropriate burn and spark generating characteristics. In certain embodiments, the amount of oxidizing agent in the initiator composition can be related to the molar amount of the oxidizers at or near the eutectic point for the fuel composition. In certain embodiments, the oxidizing agent can be the major component and in others the metal reducing agent can be the major component. Those of skill in the art are able to determine the appropriate amount of each component based on the stoichiometry of the chemical reaction and/or by routine experimentation. Also as known in the art, the particle size of the metal and the metal-containing oxidizer can be varied to determine the burn rate, with smaller particle sizes selected for a faster burn (see, for example, PCT WO 2004/01396).
  • [0085]
    In certain embodiments, an initiator composition can comprise additive materials to facilitate, for example, processing, enhance the mechanical integrity and/or determine the burn and spark generating characteristics. The additive materials can be inorganic materials and can function as binders, adhesives, gelling agents, thixotropic, and/or surfactants. Examples of gelling agents include, but are not limited to, clays such as Laponite®, Montmorillonite, Cloisite®, metal alkoxides such as those represented by the formula R—Si(OR)n and M(OR)n where n can be 3 or 4, and M can be Ti, Zr, Al, B or other metals, and colloidal particles based on transition metal hydroxides or oxides. Examples of binding agents include, but are not limited to, soluble silicates such as Na- or K-silicates, aluminum silicates, metal alkoxides, inorganic polyanions, inorganic polycations, inorganic sol-gel materials such as alumina or silica-based sols. Other useful additive materials include glass beads, diatomaceous earth, nitrocellulose, polyvinylalcohol, guor gum, ethyl cellulose, cellulose acetate, polyvinylpyrrolidone, fluorocarbon rubber (Viton) and other polymers that can function as a binder. In certain embodiments, the initiator composition can comprise more than one additive material. The components of the initiator composition comprising the metal, metal-containing oxidizing agent and/or additive material and/or any appropriate aqueous- or organic-soluble binder, can be mixed by any appropriate physical or mechanical method to achieve a useful level of dispersion and/or homogeneity. In certain embodiments, additive materials can be useful in determining certain processing, ignition, and/or burn characteristics of the initiator composition. In certain embodiments, the particle size of the components of the initiator can be selected to tailor the ignition and burn rate characteristics as is known in the art (see for example U.S. Pat. No. 5,739,460).
  • [0086]
    In certain embodiments, an initiator composition can comprise at least one metal, such as those described herein, and at least one oxidizing agent, such as, for example, a chlorate or perchlorate of an alkali metal or an alkaline earth metal or metal oxide and others disclosed herein.
  • [0087]
    Examples of initiator compositions include compositions comprising 10% Zr: 22.5% B: 67.5% KClO3; 49.) % Zr: 49.0 % MoO3 and 2.0% nitrocellulose, and 33.9% Al: 55.4% MoO3: 8.9% B: 1.8 nitrocellulose; 26.5% Al: 51.5% MoO3: 7.8% B: 14.2% Viton, in weight percent.
  • [0088]
    Other initiator compositions can be used. For example, an initiator composition that can ignite upon application of a percussive force comprises a mixture of sodium chlorate (NaClO3), phosphorous (P), and magnesium oxide (MgO).
  • [0089]
    Energy sufficient to heat the initiator composition to the auto-ignition temperature can be applied to the initiator composition and/or the support on which the initiator composition is disposed. The energy source can be any of those disclosed herein, such as resistive heating, radiation heating, inductive heating, optical heating, and percussive heating. In embodiments wherein the initiator composition is capable of absorbing the incident energy, the support can comprise a thermally insulating material. In certain embodiments, the incident energy can be applied to a thermally conductive support that can heat the initiator composition above the auto-ignition temperature by thermal conduction.
  • [0090]
    In certain embodiments, the energy source can be an electrically resistive heating element. The electrically resistive heating element can comprise any material that can maintain integrity at the auto-ignition temperature of the initiator composition. In certain embodiments, the heating element can comprise an elemental metal such as tungsten, an alloy such as Nichrome, or other material such as carbon. Materials suitable for resistive heating elements are known in the art. The resistive heating element can have any appropriate form. For example, the resistive heating element can be in the form of a wire, filament, ribbon or foil. In certain embodiments, the electrical resistance of the heating unit can range from 2 Ω to 4 Ω. The appropriate resistivity of the heating element can at least in part be determined by the current of the power source, the desired auto ignition temperature, or the desired ignition time. In certain embodiments, the auto-ignition temperature of the initiator composition can range from 200° C. to 500° C. The resistive heating element can be electrically connected, and suspended between two electrodes electrically connected to a power source.
  • [0091]
    The support can comprise one or more heating units.
  • [0092]
    An embodiment of an igniter comprising a resistive heating element is illustrated in FIG. 16. As shown in FIG. 16, resistive heating element 716 is electrically connected to electrodes 714. Electrodes 714 can be electrically connected to an external power source such as a battery (not shown). As shown in FIG. 16, electrodes 714 are disposed on a laminate material 712 such as a printed circuit material. Such materials and methods of fabricating such flexible or rigid laminated circuits are well known in the art. In certain embodiments, laminate material 712 can comprise a material that will not degrade at the temperatures reached by resistive heating element 716, by the exothermic reaction including sparks generated by initiator composition 718, and at the temperature reached during burning of the solid fuel. For example, laminate 712 can comprise Kapton®, a fluorocarbon laminate material or FR4 epoxy/fiberglass printed circuit board. Resistive heating element 716 is positioned in an opening 713 in laminate 712. Opening 713 thermally isolates resistive heating element 716 to minimize thermal dissipation and facilitate transfer of the heat generated by the resistive heating element to the initiator composition, and can provide a path for sparks ejected from initiator composition 718 to impinge upon a solid fuel (not shown).
  • [0093]
    As shown in FIG. 16, initiator composition 718 is disposed on resistive heating element 716.
  • [0094]
    The following procedure was used to apply the initiator composition to resistive heating elements.
  • [0095]
    A 0.0008 inch diameter Nichrome wire was soldered to Cu conductors disposed on a 0.005 inch thick FR4 epoxy/fiberglass printed circuit board (Onanon). The dimensions of the igniter printed circuit board were 1.82 inches by 0.25 inches. Conductor leads can extend from the printed circuit board for connection to a power source. In certain embodiments, the electrical leads can be connected to an electrical connector.
  • [0096]
    The igniter printed circuit board was cleaned by sonicating (Branson 8510R-MT) in DI water for 10 minutes, dried, sprayed with acetone and air dried.
  • [0097]
    The initiator composition comprised 0.68 grams nano-aluminum (40-70 nm diameter; Argonide Nanomaterial Technologies, Sanford, Fla.), 1.23 grams of nano-MoO3 (EM-NTO-U2; Climax Molybdenum, Henderson, Colo.), and 0.2 grams of nano-boron (33,2445-25G; Aldrich). A slurry comprising the initiator composition was prepared by adding 8.6 mL of 4.25% Viton/A500 (4.25 grams Viton in 100 mL amyl acetate (Mallinckrodt)) solution.
  • [0098]
    A 1.1 uL drop of slurry was deposited on the heating element, dried for 20 minutes, and another 0.8 uL drop of slurry comprising the initiator composition was deposited on the opposite side of the heating element.
  • [0099]
    Application of 3.0 V through a 1,000 μF capacitor from two A76 alkaline batteries to the Nichrome heating element ignited the Al:MoO3: B initiator composition within 1 to 50 msec, typically within 1 to 6 msec. When positioned within 0.12″ inches of the surface of a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent such as, for example, a fuel comprising 76.16% Zr: 19.04% MoO3: 4.8% Laponite® RDS, the sparks produced by the initiator composition ignited the solid fuel to produce a self-sustaining exothermic reaction. In certain embodiments, a 1 μL drop of the slurry comprising the initiator composition can be deposited onto the surface of the solid fuel adjacent the initiator composition disposed on the resistive heating element to facilitate ignition of the solid fuel.
  • [0100]
    The initiator composition comprising Al: MoO3: B adhered to the Nichrome wire and maintained physical integrity following mechanical and environmental testing including temperature cycling (−25° C.
    Figure US20040234699A1-20041125-P00900
    40° C.), drop testing, and impact testing.
  • [0101]
    In certain embodiments, as shown in FIG. 2D heating units can include a thermal shunt 98, shown in FIG. 2D as a cylindrical rod disposed within the heating unit. In certain embodiments, the thermal shunt can be incorporated into the solid fuel expanse as a particulate, the thermal shunt can comprise the backing member and/or the thermal shunt can be a separate element as shown. The thermal shunt can be in direct contact with the solid fuel and/or can indirectly contact the solid fuel. In certain embodiments, a thermal shunt can be capable of absorbing heat such that incorporation of a thermal shunt in a heating unit can control or reduce the maximum temperature reached by the exterior surface of the substrate forming the heating unit. For example, in certain embodiments, the thermal shunt can comprise a material capable of undergoing a phase change at or above the ignition temperature of the solid fuel. Examples of phase change materials include low melting point metals such as tin, low melting point alloys such as Wood's metal and lead-tin alloys, inorganic salts, and mixtures thereof. In certain embodiments, the thermal shunt can comprise a material that can release absorbed heat to prolong the heating time of the heating unit. In certain embodiments, a thermal shunt can comprise at least one material exhibiting a high heat capacity, such as, for example, copper, aluminum, stainless steel and glass. Examples of materials that can release absorbed heat include sugars, waxes, metal salts and other materials capable of melting during burning of the solid fuel and then undergoing crystallization as the heating unit cools, thus generating exothermic heat of crystallization, and mixtures thereof. Other materials capable of functioning as thermal shunts include porous and fibrous materials such as porous ceramic membranes and/or fiber mats, and the like. Such materials can exhibit a high surface area that can facilitate heat transfer from the reactants and reaction products to the material matrix. In certain embodiments, the porous and/or fibrous materials do not react with the reactants or reaction products produced during ignition and burn, and do not degrade and/or produce gaseous products at the temperatures achieved by the heating unit. In certain embodiments, the thermal shunt material can comprise fibers including, but not limited to, metal fibers, silica fibers, glass fibers, graphite fibers, and/or polymer fibers.
  • [0102]
    In certain embodiments, the heating units described and illustrated in FIGS. 1A-1B and 2A-2D can be used in applications wherein rapid heating is useful. In certain embodiments, a portion of the substrate can reach a maximum (peak) temperature in less than three seconds (3 sec), in certain embodiments less than 1 second (1 sec), in certain embodiments less than 500 milliseconds, and in certain embodiments less than 250 milliseconds.
  • [0103]
    A heating unit substantially as illustrated in FIG. 2B was fabricated to measure the temperature of the exterior surface of the substrate following ignition of a solid fuel. Referring to FIG. 2B, cylindrical substrate 62 was approximately 1.5 inches in length and the diameter of open receptacle 66 was 0.6 inches. Solid fuel 80 comprising 75% Zr: 25% MoO3 in weight percent was placed in the inner region in the space between the backing member 74 and the interior surface of substrate 62. A first initiator composition 82 comprising 5 mg of 10% Zr: 22.5% B: 67.5% KClO3 in weight percent was placed in the depression of the retaining member and 10 mg of a second initiator composition 94 of 10% Zr: 22.5% B : 67.5% KClO3 in weight percent was placed in the open end 76 of backing member 74 near the tapered portion of heating unit 60. Electrical leads 88, 90 from two 1.5 V batteries provided a current of 0.3 Amps to ignite first initiator composition 82, thus producing sparks to ignite second initiator composition 94. Both initiators were ignited within 1 to 20 milliseconds following application of the electrical current. Sparks produced by second initiator composition 94 ignited solid fuel 80 in the tapered nose region 64 of the cylinder. Thermocouples placed on the exterior surface of substrate 62 were used to monitor the substrate surface temperature as a function of time. The exterior substrate surface reached a maximum temperature of 400° C. in less than 100 milliseconds.
  • [0104]
    Upon ignition of the solid fuel, an exothermic oxidation-reduction reaction produces a considerable amount of energy in a short time, such as for example, in certain embodiments less than 1 second, in certain embodiments less than 500 milliseconds, and in certain embodiments less than 250 milliseconds. Examples of exothermic reactions include electrochemical reactions and metal oxidation-reduction reactions. When used in enclosed heating units, by minimizing the quantity of reactants and the reaction conditions the reaction can be controlled but can result in a slow release of heat and/or a modest temperature rise. However, in certain applications, it can be useful to rapidly heat a substrate to temperatures in excess of 200° C. within 1 second or less. Such rapid intense thermal pulses can be useful for vaporizing pharmaceutical compositions to produce aerosols. A rapid intense thermal pulse can be produced using an exothermic oxidation-reduction reaction and in particular a thermite reaction involving a metal and a metal-containing oxidizing agent. Concomitant with the rapid generation of heat, there can be a rapid generation of gaseous products and unreacted reactants with high translational energies. When sealed within an enclosure, the exothermic oxidation-reduction reaction can generate a significant increase in pressure.
  • [0105]
    Energy produced by the exothermic reaction, whether thermal, optical, mechanical, e.g. particle ejection, or chemical can generate a significant pressure when contained with a sealed enclosure. In certain embodiments, a solid fuel capable of reacting in an exothermic oxidation-reduction reaction can be used to form a heating unit. For example, solid fuel as disclosed herein can be used to thermally vaporize a drug coating to produce an aerosol of a drug for medical applications. In certain applications, such as in portable medical devices, it can be useful to contain the pyrothermic materials and products of the exothermic reaction and other chemical reactions resulting from the high temperatures within the enclosure. While containing the exothermic reaction can be accomplished by adequately sealing the enclosure to withstand the internal pressures resulting from the burning of the solid fuel as well as an initiator composition if present, it can be useful to minimize the internal pressure to ensure the safety of the heating device and facilitate device fabrication.
  • [0106]
    In certain embodiments, the pressure within the substrate can increase during and after ignition and burning of the initiator composition and the solid fuel. The increase in pressure can depend, at least in part, on the amount and composition of the solid fuel, the relative amounts of the fuel components, the density and/or degree of compaction of the solid fuel, the particle size of the fuel components, the configuration of the substrate, the amount of initiator, and/or the composition of the initiator. In certain embodiments, a solid fuel, an initiator composition, and a substrate configuration can be selected to control the pressure increase and maintain the maximum pressure within a useful operating range. The initiator composition and solid fuel can produce gas phase reaction products during ignition and burn. Thus, in certain embodiments, the pressure within the substrate can be managed by minimizing the amount of initiator composition and solid fuel disposed within the heating unit. One of skill can experimentally determine the minimum amount of initiator composition needed to reliably ignite the solid fuel. One of skill can also determine the properties, configuration, and placement of the solid fuel within a heating unit to achieve a useful substrate temperature.
  • [0107]
    In certain embodiments, the internal pressure of a heating unit can be managed or reduced by constructing the substrate, backing, and any other internal components from materials that produce minimal gas products at elevated temperatures. In certain embodiments, pressure can be managed or reduced by providing an interior volume wherein gas can be collected and/or vented when the initiator and solid fuel are burned. In certain embodiments, the interior volume can include a porous or fibrous material having a high surface area and a large interstitial volume. The interstitial volume can contain a gas generated as a result of the initiator and solid fuel reactions and can thereby reduce the pressure within the enclosure and collisions of the reactants and reaction products with the matrix of the porous or fibrous material can efficiently transfer the internal and translational energy.
  • [0108]
    The internal pressure of a heating unit during and after burning of an initiator composition and a solid fuel can vary depending on the parameters discussed above. The internal pressure of certain embodiments of heating units was measured using the fixture illustrated in FIG. 3. As shown in FIG. 3, heating unit 300 comprises a substantially-cylindrically shaped substrate 302 having a closed nose portion 304 and an open receiving end 306. A backing member 308 is disposed within the interior region of substrate 302. Backing member 308 is cylindrical in shape but of overall smaller dimensions than that of substrate 302. Tapered nose portion 310 defines an opening 312 in backing member 308. Opposing end 314 from tapered nose portion 310 of backing member 308 is open. The interior surface of substrate 302 and the exterior surface of backing member 308 define an annular shell or a gap into which a solid fuel 316 can be disposed. A plug 320 is sized for insertion into open receiving end 306 of substrate 302 and is securely sealed by an O-ring 322. Electrodes 324 in contact with an initiator composition (not shown) disposed within heating unit 300 extend through plug 320 for electrical connection to a power source (not shown) external to heating unit 300. Pressure transducer 326 for measuring the steady state pressure via line 328 within heating unit 300 can be mounted on plug 320. A dynamic pressure transducer 330 can be provided for monitoring the pressure within heating unit 300 via line 332.
  • [0109]
    A heating unit equipped with two pressure transducers, as illustrated in FIG. 3, was used to simultaneously measure the dynamic pressure and steady state pressure within a heating unit of a type as shown in FIG. 2. For dynamic pressure measurement, a high frequency shock wave/blast ICP pressure sensor (PCB, model 113A24, maximum pressure=1,000 psig) combined with a line powered ICP signal conditioner (PCB, model 484B06) was used. For steady state pressure measurement, a subminiature millivolt output type pressure transducer (Omega Engineering, model PX600-500GV, maximum pressure=500 psig) and a high performance strain gauge indicator with analog output (PCB, DP41-S-A) were used. Signals generated by the pressure transducers were recorded and stored using two oscilloscopes. To minimize the influence of pressure measurement on the performance of the heating unit, the volume of lines 328 and 332 were designed so as not to exceed 2% of the total unfilled internal volume of the heating unit. The measured internal pressure ranged from 100 psig to 300 psig, and depended primarily on the composition of the solid fuel. The contribution of the initiator composition to the internal pressure was a maximum 100 psig.
  • [0110]
    Measurements of the peak internal pressure within sealed heating units, of a type as shown in FIG. 10, following ignition of a thin film layer of solid fuel comprising a metal reducing agent and a metal-containing oxidizer are shown in FIG. 17. The experimental arrangement used to generate the results shown in FIG. 17 is described in Example 2. FIG. 17 shows that for certain embodiments, the peak pressure within a heating unit can range from 10 psig to 40 psig and correlates with the peak temperature of the exterior surface of the substrate. Also, as shown in FIG. 17, the peak pressure within the heating unit, as well as the peak temperature of the substrate surface can for the particular embodiments of heating units measure, depend on the composition of the solid fuel, and the thickness of the foil substrate.
  • [0111]
    The internal pressure within a heating unit can also be managed or reduced by incorporating materials capable of absorbing, adsorbing or reacting with gas phase reaction products. The surface of the material may intrinsically be capable of absorbing, adsorbing or reacting with the gaseous products, or can be coated or decorated with, for example, elements, compounds and/or compositions. In certain embodiments, the immediate burst of pressure resulting from the solid fuel burn can be reduced by locating an impulse absorbing material and/or coating within the heating unit. An embodiment of a heating unit comprising an impulse absorbing material is schematically illustrated in FIG. 13.
  • [0112]
    FIGS. 13A-C show a thermally conductive substrate 210, such as metal foil on which is disposed a coating of a solid fuel 212. Solid fuel 212 can comprise a metal reducing agent and a metal-containing oxidizing agent capable of forming an oxidation-reduction reaction, such as, but not limited to, any of those disclosed herein. In FIGS. 13A-C thermally conductive substrate 210 is sealed using a sealant 220 to an enclosure 218 to form the heating unit. Sealant 220 can be an adhesive or any other methods for forming a seal, such as for example, welding, soldering, fastening or crimping. An impulse absorbing material 214 is disposed between the interior surface of enclosure 218 and the interior surfaces of substrate 210 and the solid fuel 212. As shown in FIGS. 13A-C, impulse absorbing material fills the interior volume defined by the interior surfaces of the heating unit. In certain embodiments, the impulse absorbing material can fill a portion of the interior volume defined by the interior surfaces of the heating unit (not shown). The thickness of the impulse absorbing material, e.g. the dimension between the interior surface of solid fuel 212 and the interior surface of enclosure 218 can be any appropriate thickness to reduce the initial pressure impulse resulting from the burning of solid fuel 212 to an appropriate level. The appropriate thickness can vary at least in part on the amount of solid fuel, the solid fuel composition, and/or the physical characteristics of the impulse absorbing material such as porosity, density, and composition and the maximum acceptable pressure within the enclosure. It will be appreciated that above a certain thickness, additional impulse absorbing material can have limited effect on reducing the peak pressure within the heating unit. The impulse absorbing material can comprise one or more materials and one or more layers of impulse absorbing material. In certain embodiments wherein multiple layers of impulse absorbing materials are used, each layer can comprise the same or different material. In FIG. 13C, an element 216 overlays impulse absorbing material 214. Element 216 can be the same or a different impulse absorbing material, and in certain embodiments, can include a getter. FIG. 13B illustrates a cross-sectional view of a cylindrical heating unit comprising a substrate 210, a layer of solid fuel 212, and a central region filled with an impulse absorbing material 214.
  • [0113]
    In certain embodiments, the impulse absorbing material can comprise a material which can absorb the thermal and translational energy of the reactants and reaction products produced during burning of the solid fuel, and if present, an initiator composition. In certain embodiments, an initiator composition comprising, for example, any of the initiator compositions disclosed herein, can be incorporated into the sealed heating unit to initiate the self-sustaining exothermic reaction of the solid fuel. An impulse absorbing material can present a high surface area to absorb the pressure impulse of thermally and translationally hot molecules and which does not react at the temperatures reached within the heating unit during and following the burn of the solid fuel. Examples of such materials include porous materials such as ceramic membranes, and fibrous materials such as fiber mats. Hot molecules physically and/or thermally ejected from the burning solid fuel can pass through the interstitial spaces defined by porous or fibrous matrix to access a large surface area, which upon collision, can facilitate transfer of thermal and translational energy to the matrix of the impulse absorbing material, thereby reducing the peak pressure within the heating unit.
  • [0114]
    Examples of porous membranes include, but are not limited to ceramic membranes, fluorocarbon membranes, alumina membranes, polymer membranes, and membranes formed from sintered metal powders. Examples of fibrous materials include, but are not limited to, glass, silica, carbon, graphite, metals, and high temperature resistant polymers. Sponge materials can also be used. The porosity and density of the impulse absorbing material can be selected to reduce the peak pressure by an appropriate amount. For a given amount of solid fuel, composition of solid fuel, and heating unit dimensions, the appropriate porosity and density of the impulse absorbing material can be determined empirically. In certain embodiments, it can be useful to have the pores sufficiently large to facilitate entry of the thermally and translationally hot molecules to the interior of an impulse absorbing material, or to one or more additional layers of impulse absorbing materials with different porosity and/or composition to facilitate transfer of energy from the hot molecules to the impulse absorbing material.
  • [0115]
    The effect of incorporating glass fiber mats on the internal pressure of a heating unit is shown in FIG. 14. Glass fiber mats were placed over a coating of solid fuel comprising an average mass of 177 mg of 80% Zr: 20% MoO3 disposed on a 0.004 inch thick stainless steel foil, and the pressure within the enclosure measured following ignition of the solid fuel. Each glass fiber mat was 0.040 inches thick. As shown in FIG. 14, glass fiber mats significantly reduced the peak internal pressure of the heating unit. When a single mat was used, the maximum pressure within the sealed enclosure was 22 psig, when two mats were used the maximum pressure was 13 psig, and when 5 mats were used, the peak pressure was 9 psig.
  • [0116]
    The ability of glass fiber mats to reduce the temperature within a heating unit is shown in FIG. 15. The same experimental arrangement as described for FIG. 14 was used. The peak temperature measured between the solid fuel and the first mat was about 515° C. and 325° C., between the first and second mats was about 200° C. and 180° C., and between the second and third mats was less than 100° C., thus demonstrating that the internal and translational energy of the reactants and reaction products is transferred to the impulse absorbing materials.
  • [0117]
    As demonstrated by the results shown in FIG. 14, the residual pressure, e.g. the pressure 10 seconds or more after solid fuel ignition, in the heating unit was insensitive to the presence of an impulse absorbing material. Without being limited by theory, the residual pressure can be the result of gases evolved and/or produced during the burning of the solid fuel. Possible gas sources include hydrogen bonded to the metal reducing agent, and unreacted oxygen produced during the oxidation reaction and unreacted gaseous intermediates. For example, oxygen generated by the metal-containing oxidizing agent may not immediately react with the metal reducing agent, but rather can proceed through several gaseous reaction intermediates.
  • [0118]
    In certain embodiments, the residual pressure within a heating unit can be reduced by including materials capable of gettering the residual gaseous reaction products. Such materials can be included with the impulse absorbing material, intrinsic to the impulse absorbing material, and/or applied to the impulse absorbing material as a coating, deposit, layer, and the like. In certain embodiments, the getter can be coated or deposited onto a support disposed within a heating unit and/or on one or more interior surfaces of the heating unit.
  • [0119]
    Getters are materials capable of absorbing, adsorbing and/or reacting with gases and can be used to improve and/or maintain a vacuum, and/or to purify gases. Absorption refers to the process by which one material is retained by another, such as the attachment of molecules of a gas or vapor to a solid surface by physical forces. Adsorption refers to the increase in the concentration of a dissolved substance at the interface of a condensed and a gaseous or liquid phase. Getters are used for example in the semiconductor industry to reduce residual gases in high vacuum systems. In certain embodiments, getters capable of removing hydrogen gas, H2, and molecular oxygen, O2, can include, but are not limited to, compositions including metals and nonmetals, such as Ta, Zr, Tb, Ti, Al, Mg, Ba, Fe, and P. Examples of getters useful for removing H2 gas include, but are not limited to, sintered Zr/graphite powders, Zr/Al compositions, Zr/V/Fe, polymer-bound getters such as PdO/zeolite dispersed in a polymer matrix, and polydiene hydrogenation catalyst compositions. Iron-based and polymeric getters have been developed to absorb O2. Carbon and/or graphite based materials can be used to adsorb and/or absorb H2 and O2. In certain embodiments, a getter can also adsorb, absorb and/or react with volatile intermediate products or the unreacted reactants of the exothermic oxidation-reduction reaction such as, for example, MoOx, CO, CO2, and N2.
  • [0120]
    A getter can be applied to a substrate by any appropriate method. In certain embodiments, it can be useful to provide a large surface area of getter to rapidly and efficiently reduce the residual gas pressure. This can be accomplished, for example, by providing a getter formed from a porous material, such as a sintered powder, or a fibrous material. In certain embodiments, the getter can be applied to the surface of a porous or fibrous material.
  • [0121]
    Certain embodiments of heating units were used to examine the burn propagation speed of the solid fuel following ignition. The burn propagation speed refers to the speed of the burn front, which separates unburned and burned solid fuel regions. In certain embodiments, the burn propagation speed can be determined at least in part by the solid fuel composition, the particle size of the components of the solid fuel, the density or level of compaction of the solid fuel, the shape and dimensions of the solid fuel, the material forming the heating unit, and/or any internal components such as a backing member. The temporal and spatial characteristics of the burn propagation speed for cylindrically-shaped heating units were evaluated by monitoring the surface temperature of heating units using an infrared thermal imaging camera (FLIR Systems, Thermacam SC3000).
  • [0122]
    Thermal images of a cylindrically-shaped heating unit measured by infrared thermal imaging as a function of time, in milliseconds, are shown in FIGS. 4A-4F. The construction of the heating unit used to produce the thermal images is provided in Example 3. The substrate was 1.5 cm in diameter and 4.5 cm in length In FIGS. 4A-4F, two images are shown in each panel. In both images, white areas in color correspond to a surface temperature of 500° C. and black areas correspond to a surface temperature of 25° C. The top image corresponds to a front view of the heating unit and the lower image corresponds to a rear view of the heating unit, which was obtained from a reflection in a mirror mounted behind the unit. FIG. 4A shows the extent of the self-propagating wave of ignited solid fuel 100 milliseconds after ignition. FIGS. 4B-4E, taken at 200, 300, 400, and 500 milliseconds after ignition, respectively, show that the wave of ignited fuel continued to propagate along the axial direction of the heating unit. The image shown in FIG. 4F was taken at 600 milliseconds after ignition, at which time the entire surface of the substrate was heated, indicating that the solid fuel was consumed. The data gathered from this and other studies using various solid fuel compositions and heating unit configurations demonstrated that the burn propagation speed can range from 1.5 cm/sec to 50 cm/sec. Thus, in certain embodiments, the speed at which heat is transferred to a substrate forming the heating unit can be tailored as useful for certain applications.
  • [0123]
    In other studies, heating units as described in Examples 4A and 4B were fabricated and the surface temperature uniformity was evaluated by infrared thermal imaging. Heating units prepared for these studies differed from those used in the investigation of burn propagation speed only in the mass ratio of metal and oxidizing agent used to form the solid fuel. Thermal images taken 400 milliseconds after igniting the solid fuel are shown in FIGS. 5A-5B. The image shown in FIG. 5A corresponds to a heating unit comprising the solid fuel composition described in Example 4A and the image in FIG. 5B to a heating unit comprising the solid fuel composition described in Example 4B. The dimensions of the heated area were 1.5 cm by 4.5 cm. The exterior substrate surface of the heating unit used to produce the image shown in FIG. 5B is more uniform than that of the heating unit shown in FIG. 5A. In certain embodiments, the substrate surface temperature can be more uniform in heating units designed for axial flame propagation. In certain embodiments, the substrate surface temperature is considered uniformly heated if no more than 10% of the exterior surface exhibits a temperature 50° C. to 100° C. less than the average temperature of the remaining 90% of the exterior surface.
  • [0124]
    In certain embodiments, it can be useful that at least a portion of the exterior surface of the substrate be heated to a uniform temperature, and that the heated portion be heated at a similar rate. Uniform heating of at least a portion of the substrate can be facilitated by reducing the thermal mass of the substrate in the region to be heated and/or by controlling the amount of solid fuel generating heat. Uniform heating of the exterior surface of the substrate can be useful for vaporizing a compound disposed on the exterior substrate surface in a short period of time to form an aerosol comprising the vaporized compound having high yield and purity. As an example, uniform heating of a 1.3 inch by 1.3 inch substrate area can be achieved by applying a 0.00163±0.000368 inch thick layer of solid fuel onto a 0.004 inch thick foil. Upon ignition, the surface of the foil opposing the surface on which 0.18 g of the solid fuel is applied can reach a maximum temperature of 440° C. over the 1.3 inch by 1.3 inch area at 250 msec after ignition. As will be appreciated by one of skill in the art, the fuel thickness selected will depend on the fuel composition, the foil thickness, and the desired temperature.
  • [0125]
    Examples 5-7 provide heating units prepared and evaluated for pressure during burn, burn propagation speed, and substrate temperature uniformity. The heating unit described in Example 5 was comprised of a solid fuel composition of Zr, MoO3, KClO3, nitrocellulose, and diatomaceous earth. After remote ignition of the solid fuel from the tip of the heating unit (opening 312 in FIG. 3), the internal pressure increased to 150 psig during the burn period of 0.3 seconds. One minute after burn, the residual pressure was under 60 psig. The burn propagation speed was measured by infrared thermal imaging to be 13 cm/sec. With respect to surface temperature uniformity, no obvious cold spots were observed. (A cold spot, for purposes of Examples 5-7 herein, is defined as a portion of the surface exhibiting a temperature which is 50° C. to 100° C. less than the average temperature of the remaining 90% of the exterior surface.)
  • [0126]
    The heating unit prepared as described in Example 6 contained a solid fuel composition comprised of Zr, MoO3, and nitrocellulose. The gap or annular shell between the substrate and backing member was 0.020 inches. The external surface of the backing member was coated with initiator composition to increase the burn propagation speed. The solid fuel was remotely ignited from the tip of the heating unit (opening 312 in FIG. 3). The internal pressure increased to 200 psig during the reaction period of 0.25 seconds, and the residual pressure was under 60 psig. The burn propagation speed was 15 cm/sec. With respect to surface temperature uniformity, no obvious cold spots were observed.
  • [0127]
    The heating unit prepared as described in Example 7 contained a solid fuel composition of Al, MoO3, and nitrocellulose. The solid fuel was placed in a 0.020-inch annular shell gap between the substrate and the backing member. The solid fuel was directly ignited near the plug. The internal pressure increased to 300 psig during the reaction period of less than 5 milliseconds. The residual pressure was under 60 psig. The exterior surface of the substrate was uniformly heated, with between 5 percent to 10 percent of the exterior surface exhibiting a temperature 50° C. to 100° C. less than that of the remaining exterior surface.
  • DRUG SUPPLY UNIT
  • [0128]
    Certain embodiments include a drug supply unit comprising a heating unit as described herein. A drug supply unit can be used in a drug delivery device where a drug is to be thermally vaporized and then condensed for administration to a user. In certain embodiments, the drug condensate can be administered by inhalation, nasal ingestion, or topically. Drug refers to any compound for therapeutic use or non-therapeutic use, including therapeutic agents and substances. Therapeutic agent refers to any compound for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and any compound used in the mitigation or treatment of symptoms of disease. Whereas, substances refer to compounds used for a non-therapeutic use, typically for a recreational or experimental purpose.
  • [0129]
    [0129]FIGS. 6A-6C schematically illustrate cross-sectional views of a drug supply unit 100 comprising a heating unit similar to that described in FIG. 2B. More specifically, FIGS. 6A-6C illustrate a drug supply unit 100 having a film of drug disposed on the exterior substrate surface (FIG. 6A); ignition of the heating unit (FIG. 6B); and generation of a wave of heat effective to vaporize the drug film (FIG. 6C). With initial reference to FIG. 6A, drug supply unit 100 comprises a heating unit 102, similar to that described in FIG. 2B. In FIGS. 6A-B, a substantially cylindrically-shaped, heat-conductive substrate 104 has an exterior surface 106 and an interior surface 108, which define an inner region 112. A film 110 of drug can be disposed on all or a portion of exterior surface 106.
  • [0130]
    In certain embodiments, film 110 can be applied to exterior substrate surface 106 by any appropriate method and can depend at least in part on the physical properties of the drug and the final thickness of the film. In certain embodiments, methods of applying a drug to the exterior substrate surface include, but are not limited to, brushing, dip coating, spray coating, screen printing, roller coating, inkjet printing, vapor-phase deposition, spin coating, and the like. In certain embodiments, the drug can be prepared as a solution comprising at least one solvent and applied to the exterior surface. In certain embodiments, a solvent can comprise a volatile solvent such as, for example, but not limitation, acetone or isopropanol. In certain embodiments, the drug can be applied to the exterior surface of the substrate as a melt. In certain embodiments, the drug can be applied to a support having a release coating and transferred to a substrate from the support. For drugs that are liquid at room temperature, thickening agents can be admixed with the drug to produce a viscous composition comprising the drug that can be applied to the exterior substrate surface by any appropriate method, including those described herein. In certain embodiments, a film of compound can be formed during a single application or can be formed during repeated applications to increase the final thickness of the film. In certain embodiments, the final thickness of a film of drug disposed on the exterior substrate surface can be less than 50 μm, in certain embodiments less than 20 μm and in certain embodiments less than 10 μm, in certain embodiments the film thickness can range from 0.02 μm to 20 μm, and in certain embodiments can range from 0.1 μm to 10 μm.
  • [0131]
    In certain embodiments, the film can comprise a therapeutically effective amount of at least one drug. Therapeutically effective amount refers to an amount sufficient to affect treatment when administered to a patient or user in need of treatment. Treating or treatment of any disease, condition, or disorder refers to arresting or ameliorating a disease, condition or disorder, reducing the risk of acquiring a disease, condition or disorder, reducing the development of a disease, condition or disorder or at least one of the clinical symptoms of the disease, condition or disorder, or reducing the risk of developing a disease, condition or disorder or at least one of the clinical symptoms of a disease or disorder. Treating or treatment also refers to inhibiting the disease, condition or disorder, either physically, e.g. stabilization of a discernible symptom, physiologically, e.g., stabilization of a physical parameter, or both, and inhibiting at least one physical parameter that may not be discernible to the patient. Further, treating or treatment refers to delaying the onset of the disease, condition or disorder or at least symptoms thereof in a patient which may be exposed to or predisposed to a disease, condition or disorder even though that patient does not yet experience or display symptoms of the disease, condition or disorder. In certain embodiments, the drug film can comprise one or more pharmaceutically acceptable carriers, adjuvants, and/or excipients. Pharmaceutically acceptable refers to approved or approvable by a regulatory agency of the Federal or a state government or listed in the U.S Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans.
  • [0132]
    As shown in FIGS. 6A-6C, substrate 104 of drug supply unit 100 can define an inner region 112 in which a solid fuel 114 can be disposed. As shown, solid fuel 114 can be disposed as an annular shell defined by interior substrate surface 108 and an inner, cylindrical backing member 118. A first initiator composition 120 can be located at one end of cylindrical backing member 118 and a second initiator composition 122 can be located at the opposing end of cylindrical backing member 118. First initiator composition 120 can be in physical contact with an electrically resistive heating element via electrical leads 124, 126 to a power source (not shown).
  • [0133]
    As shown in FIGS. 6B, application of an electrical current provided by a power source (not shown) to leads 124, 126 can cause initiator composition 120 to produce sparks, such as sparks 128, 130 that can be directed toward second initiator composition 122. Ignition of second initiator composition 122 can ignite solid fuel 114 in the region indicated by arrows 132, 134. Igniting solid fuel 114 in the region indicated by arrows 132, 134 effectuates a self-propagating wave of burning solid fuel, as schematically illustrated in FIG. 6C. In FIG. 6C, the self-propagating burn is indicated by arrows 136, 138, 140, 142 with the solid fuel burn propagating from the point of ignition through the solid fuel. As the solid fuel burns, heat can be produced that can be conducted through substrate 104 causing vaporization of drug film 110 disposed on external substrate surface 106. In FIG. 6C, thermally vaporized drug is illustrated as the “cloud” of drug 144. In certain embodiments, as illustrated in FIG. 6C, vaporization of the drug occurs in the direction of arrows 136, 138, 140, 142, where the film nearest the ignition point of the solid fuel is vaporized first, followed by vaporization in regions along the length of drug supply unit 100. As shown in FIG. 6C, thermally vaporized drug 144 is illustrated at the tapered region of drug supply unit 100, and drug film not yet vaporized from the exterior surface 106 is illustrated at point 110.
  • [0134]
    [0134]FIGS. 7A-7E represent high-speed photographs showing the thermal generation of a vapor from a drug supply unit similar to that described in FIGS. 6A-6C. FIG. 7A shows a heat-conductive substrate 4 cm in length coated with a 3 μm to 5 μm thick film of the therapeutic agent alprazolam. The drug-coated substrate was placed in a chamber through which a stream of air was flowing in an upstream-to-downstream direction, indicated by the arrow in FIG. 7A, at a rate of 15 L/min. Solid fuel contained in the heating unit was ignited to heat the substrate. The progression of drug vaporization from the exterior surface of the drug supply unit was monitored using real-time photography. FIGS. 7B-7E show the sequence of thermal vaporization at time intervals of 150 msec, 250 msec, 500 msec, and 1,000 msec, following ignition of an initiator composition, respectively. The cloud of thermal vapor formed from the drug film is visible in the photographs. Complete vaporization of the drug film was achieved in less than 1,000 msec.
  • [0135]
    The drug supply unit is configured such that the solid fuel heats a portion of the exterior surface of the substrate to a temperature sufficient to thermally vaporize the drug in certain embodiments within at least 3 seconds following ignition of the solid fuel, in other embodiments within 1 second following ignition of the solid fuel, in other embodiments within 800 milliseconds following ignition of the solid fuel, in other embodiments within 500 milliseconds following ignition of the solid fuel, and in other embodiments within 250 milliseconds following ignition of the solid fuel.
  • [0136]
    In certain embodiments, a drug supply unit can generate an aerosol comprising a drug that can be inhaled directly by a user and/or can be mixed with a delivery vehicle, such as a gas, to produce a stream for delivery, e.g., via a spray nozzle, to a topical site for a variety of treatment regimens, including acute or chronic treatment of a skin condition, administration of a drug to an incision site during surgery, or to an open wound.
  • [0137]
    In certain embodiments, rapid vaporization of a drug film can occur with minimal thermal decomposition of the drug. For example, in certain embodiments, less than 10% of the drug is decomposed during thermal vaporization, and in certain embodiments, less than 5% of the drug is decomposed during thermal vaporization. In certain embodiments, a drug can undergo a phase transition to a liquid state and then to a gaseous state, or can sublime, i.e., pass directly from a solid state to a gaseous state. In certain embodiments, a drug can include a pharmaceutical compound. In certain embodiments, the drug can comprise a therapeutic compound or a non-therapeutic compound. A non-therapeutic compound refers to a compound that can be used for recreational, experimental, or pre-clinical purposes. Classes of drugs that can be used include, but are not limited to, anesthetics, anticonvulsants, antidepressants, antidiabetic agents, antidotes, antiemetics, antihistamines, anti-infective agents, antineoplastics, antiparkisonian drugs, antirheumatic agents, antipsychotics, anxiolytics, appetite stimulants and suppressants, blood modifiers, cardiovascular agents, central nervous system stimulants, drugs for Alzheimer's disease management, drugs for cystic fibrosis management, diagnostics, dietary supplements, drugs for erectile dysfunction, gastrointestinal agents, hormones, drugs for the treatment of alcoholism, drugs for the treatment of addiction, immunosuppressives, mast cell stabilizers, migraine preparations, motion sickness products, drugs for multiple sclerosis management, muscle relaxants, nonsteroidal anti-inflammatories, opioids, other analgesics and stimulants, opthalmic preparations, osteoporosis preparations, prostaglandins, respiratory agents, sedatives and hypnotics, skin and mucous membrane agents, smoking cessation aids, Tourette's syndrome agents, urinary tract agents, and vertigo agents.
  • [0138]
    Examples of anesthetic include ketamine and lidocaine.
  • [0139]
    Examples of anticonvulsants include compounds from one of the following classes: GABA analogs, tiagabine, vigabatrin; barbiturates such as pentobarbital; benzodiazepines such as clonazepam; hydantoins such as phenytoin; phenyltriazines such as lamotrigine; miscellaneous anticonvulsants such as carbamazepine, topiramate, valproic acid, and zonisamide.
  • [0140]
    Examples of antidepressants include amitriptyline, amoxapine, benmoxine, butriptyline, clomipramine, desipramine, dosulepin, doxepin, imipramine, kitanserin, lofepramine, medifoxamine, mianserin, maprotoline, mirtazapine, nortriptyline, protriptyline, trimipramine, venlafaxine, viloxazine, citalopram, cotinine, duloxetine, fluoxetine, fluvoxamine, milnacipran, nisoxetine, paroxetine, reboxetine, sertraline, tianeptine, acetaphenazine, binedaline, brofaromine, cericlamine, clovoxamine, iproniazid, isocarboxazid, moclobemide, phenyhydrazine, pheneizine, selegiline, sibutramine, tranylcypromine, ademetionine, adrafinil, amesergide, amisulpride, amperozide, benactyzine, bupropion, caroxazone, gepirone, idazoxan, metralindole, milnacipran, minaprine, nefazodone, nomifensine, ritanserin, roxindole, S-adenosylmethionine, escitalopram, tofenacin, trazodone, tryptophan, and zalospirone.
  • [0141]
    Examples of antidiabetic agents include pioglitazone, rosiglitazone, and troglitazone.
  • [0142]
    Examples of antidotes include edrophonium chloride, flumazenil, deferoxamine, nalmefene, naloxone, and naltrexone.
  • [0143]
    Examples of antiemetics include alizapride, azasetron, benzquinamide, bromopride, buclizine, chlorpromazine, cinnarizine, clebopride, cyclizine, diphenhydramine, diphenidol, dolasetron, droperidol, granisetron, hyoscine, lorazepam, dronabinol, metoclopramide, metopimazine, ondansetron, perphenazine, promethazine, prochlorperazine, scopolamine, triethylperazine, trifluoperazine, triflupromazine, trimethobenzamide, tropisetron, domperidone, and palonosetron.
  • [0144]
    Examples of antihistamines include astemizole, azatadine, brompheniramine, carbinoxamine, cetrizine, chlorpheniramine, cinnarizine, clemastine, cyproheptadine, dexmedetomidine, diphenhydramine, doxylamine, fexofenadine, hydroxyzine, loratidine, promethazine, pyrilamine and terfenidine.
  • [0145]
    Examples of anti-infective agent include compounds selected from one of the following classes: antivirals such as efavirenz; AIDS adjunct agents such as dapsone; aminoglycosides such as tobramycin; antifungals such as fluconazole; antimalarial agents such as quinine; antituberculosis agents such as ethambutol; β-lactams such as cefmetazole, cefazolin, cephalexin, cefoperazone, cefoxitin, cephacetrile, cephaloglycin, cephaloridine; cephalosporins, such as cephalosporin C, cephalothin; cephamycins such as cephamycin A, cephamycin B, and cephamycin C, cephapirin, cephradine; leprostatics such as clofazimine; penicillins such as ampicillin, amoxicillin, hetacillin, carfecillin, carindacillin, carbenicillin, amylpenicillin, azidocillin, benzylpenicillin, clometocillin, cloxacillin, cyclacillin, methicillin, nafcillin, 2-pentenylpenicillin, penicillin N, penicillin O, penicillin S, penicillin V, dicloxacillin; diphenicillin; heptylpenicillin; and metampicillin; quinolones such as ciprofloxacin, clinafloxacin, difloxacin, grepafloxacin, norfloxacin, ofloxacine, temafloxacin; tetracyclines such as doxycycline and oxytetracycline; miscellaneous anti-infectives such as linezolide, trimethoprim and sulfamethoxazole.
  • [0146]
    Examples of anti-neoplastic agents include droloxifene, tamoxifen, and toremifene.
  • [0147]
    Examples of antiparkisonian drugs include amantadine, baclofen, biperiden, benztropine, orphenadrine, procyclidine, trihexyphenidyl, levodopa, carbidopa, andropinirole, apomorphine, benserazide, bromocriptine, budipine, cabergoline, eliprodil, eptastigmine, ergoline, galanthamine, lazabemide, lisuride, mazindol, memantine, mofegiline, pergolide, piribedil, pramipexole, propentofylline, rasagiline, remacemide, ropinerole, selegiline, spheramine, terguride, entacapone, and tolcapone.
  • [0148]
    Examples of antirheumatic agents include diclofenac, hydroxychloroquine and methotrexate.
  • [0149]
    Examples of antipsychotics include acetophenazine, alizapride, amisulpride, amoxapine, amperozide, aripiprazole, benperidol, benzquinamide, bromperidol, buramate, butaclamol, butaperazine, carphenazine, carpipramine, chlorpromazine, chlorprothixene, clocapramine, clomacran, clopenthixol, clospirazine, clothiapine, clozapine, cyamemazine, droperidol, flupenthixol, fluphenazine, fluspirilene, haloperidol, loxapine, melperone, mesoridazine, metofenazate, molindrone, olanzapine, penfluridol, pericyazine, perphenazine, pimozide, pipamerone, piperacetazine, pipotiazine, prochlorperazine, promazine, quetiapine, remoxipride, risperidone, sertindole, spiperone, sulpiride, thioridazine, thiothixene, trifluperidol, triflupromazine, trifluoperazine, ziprasidone, zotepine, and zuclopenthixol.
  • [0150]
    Examples of anxiolytics include alprazolam, bromazepam, oxazepam, buspirone, hydroxyzine, mecloqualone, medetomidine, metomidate, adinazolam, chlordiazepoxide, clobenzepam, flurazepam, lorazepam, loprazolam, midazolam, alpidem, alseroxlon, amphenidone, azacyclonol, bromisovalum, captodiamine, capuride, carbcloral, carbromal, chloral betaine, enciprazine, flesinoxan, ipsapiraone, lesopitron, loxapine, methaqualone, methprylon, propanolol, tandospirone, trazadone, zopiclone, and zolpidem.
  • [0151]
    An example of an appetite stimulant is dronabinol.
  • [0152]
    Examples of appetite suppressants include fenfluramine, phentermine and sibutramine.
  • [0153]
    Examples of blood modifiers include cilostazol and dipyridamol.
  • [0154]
    Examples of cardiovascular agents include benazepril, captopril, enalapril, quinapril, ramipril, doxazosin, prazosin, clonidine, labetolol, candesartan, irbesartan, losartan, telmisartan, valsartan, disopyramide, flecanide, mexiletine, procainamide, propafenone, quinidine, tocainide, amiodarone, dofetilide, ibutilide, adenosine, gemfibrozil, lovastatin, acebutalol, atenolol, bisoprolol, esmolol, metoprolol, nadolol, pindolol, propranolol, sotalol, diltiazem, nifedipine, verapamil, spironolactone, bumetanide, ethacrynic acid, furosemide, torsemide, amiloride, triamterene, and metolazone.
  • [0155]
    Examples of central nervous system stimulants include amphetamine, brucine, caffeine, dexfenfluramine, dextroamphetamine, ephedrine, fenfluramine, mazindol, methyphenidate, pemoline, phentermine, sibutramine, and modafinil.
  • [0156]
    Examples of drugs for Alzheimer's disease management include donepezil, galanthamine and tacrin.
  • [0157]
    Examples of drugs for cystic fibrosis management include CPX, IBMX, XAC and analogues; 4-phenylbutyric acid; genistein and analogous isoflavones; and milrinone.
  • [0158]
    Examples of diagnostic agents include adenosine and aminohippuric acid.
  • [0159]
    Examples of dietary supplements include melatonin and vitamin-E.
  • [0160]
    Examples of drugs for erectile dysfunction include tadalafil, sildenafil, vardenafil, apomorphine, apomorphine diacetate, phentolamine, and yohimbine.
  • [0161]
    Examples of gastrointestinal agents include loperamide, atropine, hyoscyamine, famotidine, lansoprazole, omeprazole, and rebeprazole.
  • [0162]
    Examples of hormones include: testosterone, estradiol, and cortisone.
  • [0163]
    Examples of drugs for the treatment of alcoholism include naloxone, naltrexone, and disulfiram.
  • [0164]
    Examples of drugs for the treatment of addiction it is buprenorphine.
  • [0165]
    Examples of immunosupressives includemycophenolic acid, cyclosporin, azathioprine, tacrolimus, and rapamycin.
  • [0166]
    Examples of mast cell stabilizers include cromolyn, pemirolast, and nedocromil.
  • [0167]
    Examples of drugs for migraine headache include almotriptan, alperopride, codeine, dihydroergotamine, ergotamine, eletriptan, frovatriptan, isometheptene, lidocaine, lisuride, metoclopramide, naratriptan, oxycodone, propoxyphene, rizatriptan, sumatriptan, tolfenamic acid, zolmitriptan, amitriptyline, atenolol, clonidine, cyproheptadine, diltiazem, doxepin, fluoxetine, lisinopril, methysergide, metoprolol, nadolol, nortriptyline, paroxetine, pizotifen, pizotyline, propanolol, protriptyline, sertraline, timolol, and verapamil.
  • [0168]
    Examples of motion sickness products include diphenhydramine, promethazine, and scopolamine.
  • [0169]
    Examples of drugs for multiple sclerosis management include bencyclane, methylprednisolone, mitoxantrone, and prednisolone.
  • [0170]
    Examples of muscle relaxants include baclofen, chlorzoxazone, cyclobenzaprine, methocarbamol, orphenadrine, quinine, and tizanidine.
  • [0171]
    Examples of nonsteroidal anti-inflammatory drugs include aceclofenac, acetaminophen, alminoprofen, amfenac, aminopropylon, amixetrine, aspirin, benoxaprofen, bromfenac, bufexamac, carprofen, celecoxib, choline, salicylate, cinchophen, cinmetacin, clopriac, clometacin, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, indoprofen, ketoprofen, ketorolac, mazipredone, meclofenamate, nabumetone, naproxen, parecoxib, piroxicam, pirprofen, rofecoxib, sulindac, tolfenamate, tolmetin, and valdecoxib.
  • [0172]
    Examples of opioid drugs include alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, carbiphene, cipramadol, clonitazene, codeine, dextromoramide, dextropropoxyphene, diamorphine, dihydrocodeine, diphenoxylate, dipipanone, fentanyl, hydromorphone, L-alpha acetyl methadol, lofentanil, levorphanol, meperidine, methadone, meptazinol, metopon, morphine, nalbuphine, nalorphine, oxycodone, papaveretum, pethidine, pentazocine, phenazocine, remifentanil, sufentanil, and tramadol.
  • [0173]
    Examples of other analgesic drugs include apazone, benzpiperylon, benzydramine, caffeine, clonixin, ethoheptazine, flupirtine, nefopam, orphenadrine, propacetamol, and propoxyphene.
  • [0174]
    Examples of opthalmic preparation drugs include ketotifen and betaxolol.
  • [0175]
    Examples of osteoporosis preparation drugs alendronate, estradiol, estropitate, risedronate and raloxifene.
  • [0176]
    Examples of prostaglandin drugs include epoprostanol, dinoprostone, misoprostol, and alprostadil.
  • [0177]
    Examples of respiratory agents include albuterol, ephedrine, epinephrine, fomoterol, metaproterenol, terbutaline, budesonide, ciclesonide, dexamethasone, flunisolide, fluticasone propionate, triamcinolone acetonide, ipratropium bromide, pseudoephedrine, theophylline, montelukast, zafirlukast, ambrisentan, bosentan, enrasentan, sitaxsentan, tezosentan, iloprost, treprostinil, and pirfenidone
  • [0178]
    Examples of sedative and hypnotic drugs include butalbital, chlordiazepoxide, diazepam, estazolam, flunitrazepam, flurazepam, lorazepam, midazolam, temazepam, triazolam, zaleplon, zolpidem, and zopiclone.
  • [0179]
    Examples of skin and mucous membrane agents include isotretinoin, bergapten and methoxsalen.
  • [0180]
    Examples of smoking cessation aids include nicotine and varenicline.
  • [0181]
    An example of a Tourette's syndrome agent includes pimozide.
  • [0182]
    Examples of urinary tract agents include tolteridine, darifenicin, propantheline bromide, and oxybutynin.
  • [0183]
    Examples of vertigo agents include betahistine and meclizine.
  • [0184]
    In certain embodiments, a drug can further comprise substances to enhance, modulate and/or control release, aerosol formation, intrapulmonary delivery, therapeutic efficacy, therapeutic potency, stability, and the like. For example, to enhance therapeutic efficacy a drug can be co-administered with one or more active agents to increase the absorption or diffusion of the first drug through the pulmonary alveoli, or to inhibit degradation of the drug in the systemic circulation. In certain embodiments, a drug can be co-administered with active agents having pharmacological effects that enhance the therapeutic efficacy of the drug. In certain embodiments, a drug can comprise compounds that can be used in the treatment of one or more diseases, conditions, or disorders. In certain embodiments, a drug can comprise more than one compound for treating one disease, condition, or disorder, or for treating more than one disease, condition, or disorder.
  • THIN FILM DRUG SUPPLY UNIT
  • [0185]
    An embodiment of a thin film drug supply unit is illustrated in FIGS. 10A-10B. FIG. 10A illustrates a perspective view, and FIG. 10B an assembly view of a thin film drug supply unit 500. Thin film drug supply unit 500 comprises, as shown in FIG. 10B, a thin film heating unit 530 on which is disposed a drug 514 to be thermally vaporized. As shown in FIG. 10A, thin film heating unit 530 comprises a first and a second substrate 510, and a spacer 518.
  • [0186]
    As shown, first and second substrates 510 include an area comprising solid fuel 512 disposed on the interior surface, and an area comprising a drug 514 to be vaporized disposed on the exterior surface. First and second substrates 510 can comprise a thermally conductive material such as those described herein, including, for example, metals, ceramics, and thermally conductive polymers. In certain embodiments, substrates 510 can comprise a metal, such as, but not limited to, stainless steel, copper, aluminum, and nickel, or an alloy thereof. Substrates can have one or more layers, and the multiple layers can comprise different materials. For example, a substrate can comprise multiple layers of laminated metal foils, and/or can comprise thin films of one or more materials deposited on the surface. The multiple layers can be used for example to determine the thermal properties of the substrate and/or can be used to determine the reactivity of the surface with respect to a compound disposed on the exterior surface. A multilayer substrate can have regions comprising different materials. The thickness of substrates 510 can be thin to facilitate heat transfer from the interior to the exterior surface and/or to minimize the thermal mass of the device. In certain embodiments, a thin substrate can facilitate rapid and homogeneous heating of the exterior surface with a lesser amount of solid fuel compared to a thicker substrate. Substrate 510 can also provide structural support for solid fuel 512 and drug film 514. In certain embodiments, substrates 510 can comprise a metal foil. In certain embodiments, the thickness of substrates 510 can range from 0.001 inches to 0.020 inches, in certain embodiments from 0.001 inches to 0.010 inches, in certain embodiments from 0.002 inches to 0.006 inches, and in certain embodiments from 0.002 inches to 0.005 inches. The use of lesser amounts of solid fuel can facilitate control of the heating process as well as facilitate miniaturization of a drug supply unit.
  • [0187]
    In certain embodiments, the thickness of substrates 510 can vary across the surface. For example, a variable thickness can be useful for controlling the temporal and spatial characteristics of heat transfer and/or to facilitate sealing of the edges of substrates 510, for example, to spacer 518, opposing substrate 510, or to another support (not shown). In certain embodiments, substrates 510 can exhibit a homogeneous or nearly homogeneous thickness in the region of the substrate on which solid fuel 512 and drug 514 are disposed to facilitate achieving a homogeneous temperature across that region of the substrate on which the solid fuel is disposed. Homogeneous heating of the substrate can facilitate the production of an aerosol comprising a high purity of a drug or pharmaceutical composition and maximize the yield of drug initially deposited on the substrate forming an aerosol.
  • [0188]
    Substrates 510 can comprise an area of solid fuel 512 disposed on the interior surface, e.g. the surface facing opposing substrate 510. An appropriate amount of solid fuel 512 can in part be determined by the thermal vaporization or sublimation temperature of the drug, the amount of drug to be vaporized, the thickness and thermal conductivity of the substrate, the composition of the solid fuel, and the temporal characteristics of the intended thermal vaporization process. Solid fuel 512 can be applied to substrate 510 using any appropriate method. For example, solid fuel 512 can be applied to substrate 510 by brushing, dip coating, screen printing, roller coating, spray coating, inkjet printing, stamping, spin coating, and the like. To facilitate processing, solid fuel 510 can comprise at least one additive material, and/or a solvent, as disclosed herein. In certain embodiments, solid fuel 512 can be formed as a preformed sheet that can be cut to a specific dimension and subsequently applied to substrate 510. In certain embodiments, the solid fuel can be applied to a support, and transferred to a substrate as a preformed section. Solid fuel 512 can be applied to a portion of substrates 510 as a thin film or layer.
  • [0189]
    In certain embodiments, solid fuel 512 can comprise a mixture of Zr/MoO3, Zr/Fe2O3, Al/MoO3, or Al/Fe2O3. In certain embodiments, the amount of metal reducing agent can range from 60 wt % to 90 wt %, and the amount of metal-containing oxidizing agent can range from 40 wt % to 10 wt %. In certain embodiments, higher ratios of metal reducing agent can cause the solid fuel to burn slower and at a lower temperature, whereas lower ratios of metal reducing agent can cause the solid fuel to burn faster and reach a higher maximum temperature. Regardless of the weight percent ratios of the metal reducing agent and metal-containing oxidizing agent, a solid fuel can comprise a stoichiometric amount of metal reducing agent and metal-containing oxidizing agent. For example, the balanced Zr: Fe2O3 metal oxidation-reduction reaction can be written as:
  • [0190]
    3Zr+2Fe2O3 → 3ZrO2+4Fe A stoichiometric amount of Zr: Fe2O3 for this reaction is 1: 1.67 by weight.
  • [0191]
    Drug 514 can be disposed on the exterior surface of substrates 510. The amount of drug 514 disposed on the exterior surface of substrate 510 can be any appropriate amount. For example, the amount of drug 514 can be a therapeutically effective amount. A therapeutically effective amount can be determined by the potency of the drug, the clinical indications, and the mode of administration. In certain embodiments, thin film drug supply unit can be configured to thermally vaporize more than 95% of the drug, and in certain embodiments, greater than 98% of the drug, with minimal degradation of the drug. The aerosol formed using a drug supply unit can comprise greater than 90% of a drug applied to a substrate, and in certain embodiments greater than 95% of a drug applied to a substrate. The yield and purity of the aerosol can be controlled by and selected based on the temporal characteristics and magnitude of the thermal impulse transferred to the compound.
  • [0192]
    The relationship of the yield and purity of an aerosol comprising a pharmaceutical compound on the substrate temperature and mass of solid fuel for certain embodiments is shown in FIG. 18. Thin film drug supply units substantially as shown in FIGS. 10A and 10B, and described in Example 9 were used to produce the measurements shown in FIG. 18. The experimental arrangement used to analyze the percent yield and percent purity of the aerosol comprising a vaporized drug is described in Example 10. As shown in FIG. 18, at substrate temperatures ranging from about 355° C. to about 425° C., the percent yield of drug forming the aerosol was greater than about 85% and the percent purity was greater than about 90%. The percent yield refers to the ratio of the total solid weight of the aerosol to the weight of the drug initially deposed on the substrate times 100. Factors that can reduce the percent yield include incomplete vaporization of the drug and redeposition of the drug on the substrate.
  • [0193]
    The percent purity, with respect to the aerosol purity, refers to the fraction of drug composition in the aerosol/ the fraction of drug composition in the aerosol plus drug degradation products times 100. Thus purity is relative with regard to the purity of the starting material. For example, when the starting drug or drug composition used for substrate coating contained detectable impurities, the reported purity of the aerosol does not include those impurities present in the starting material that were also found in the aerosol, e.g., in certain cases if the starting material contained a 1% impurity and the aerosol was found to contain the identical 1% impurity, the aerosol purity may nevertheless be reported as >99% pure, reflecting the fact that the detectable 1% purity was not produced during the vaporization-condensation aerosol generation process.
  • [0194]
    Factors that can reduce the percent purity of the aerosol include degradation of the drug during thermal vaporization. Depending at least in part on the composition and thermal properties of a particular drug or pharmaceutical composition, the appropriate thermal vaporization temperature to produce an aerosol comprising the particular drug or pharmaceutical composition having high yield and purity can be determined as set forth in U.S. application Ser. No. 10/718,982, filed Nov. 20, 2003.
  • [0195]
    Drug 514 can be applied to substrate 510 using any appropriate method, such as for example, brushing, dip coating, screen printing, roller coating, spray coating, inkjet printing, stamping, vapor deposition, and the like. Drug 514 can also be applied to a support having a release layer and transferred to substrate 510. Drug 514 can be suspended in a volatile solvent such as, for example, but not limited to, acetone or isopropanol to facilitate application. A volatile solvent can be removed at room temperature or at elevated temperature, with or without application of a vacuum. In certain embodiments, the solvent can comprise a pharmaceutically acceptable solvent. In certain embodiments, residual solvent can be reduced to a pharmaceutically acceptable level.
  • [0196]
    Drug 514 can be disposed on substrate 510 in any appropriate form such as a solid, viscous liquid, liquid, crystalline solid, or powder. In certain embodiments, the film of drug can be crystallized after disposition on the substrate.
  • [0197]
    As shown in FIGS. 10A-10B, a drug supply unit can comprise an igniter 520. In certain embodiments, igniter 520 can comprise an initiator composition 522 disposed on an electrically resistive heating element connected to electrical leads disposed between two strips of insulating materials (not shown). The electrical leads can be connected to a power source (not shown). Initiator composition 522 can comprise any of the initiator compositions or compositions described herein. In certain embodiments, the ignition temperature of initiator composition can range from 200° C. to 500° C. The electrically resistive material can comprise a material capable of generating heat when electrical current is applied. For example, the electrically resistive material can be a metal such as nichrome, tungsten or graphite. An initiator composition can be disposed on the surface of the electrically resistive material such that when the electrically resistive material is heated to the ignition temperature of the initiator composition, the initiator composition can ignite to produce sparks. An initiator composition can be applied to the electrically resistive heating element by depositing a slurry comprising the initiator composition and drying. In certain embodiments, an initiator composition can be deposited on a solid fuel at a position such that when assembled, the initiator composition forming the igniter is adjacent to the initiator composition deposited on the solid fuel. Having initiator composition on at least a portion of the solid fuel can increase the speed of ignition and the reliability of the ignition process.
  • [0198]
    The electrically resistive heating element can be connected to electrical conductors. The heating element can be soldered or electrically connected to conductors, such as, Cu conductors or graphite ink traces, disposed on an electrically insulating substrate, such as a polyimide, polyester, or fluoropolymer. The conductors can be disposed between two opposing layers of the electrically insulating material such as flexible or rigid printed circuit board materials. The heating element on which an initiator composition is disposed can be exposed through an opening in the end of ignition assembly 520.
  • [0199]
    Igniter 520 can be positioned with respect to solid fuel 512 such that sparks produced by initiator composition 522 can be directed toward solid fuel area 512, causing solid fuel 512 to ignite and burn. Initiator composition 522 can be located in any position such that sparks produced by the initiator can cause solid fuel 512 to ignite. The location of initiator composition 522 with respect to solid fuel 512 can determine the direction in which solid fuel 512 burns. For example, initiator composition 522 can be located to cause solid fuel 512 to burn in any direction with respect to the airflow including in the same direction of airflow, opposite the direction of airflow, or normal the direction of airflow. The direction of solid fuel burn with respect to airflow can influence the average particle diameter of particulates comprising the thermally vaporized drug forming the aerosol. For example, in certain embodiments, solid fuel burn opposite the direction of airflow can produce smaller diameter particles than when the direction of solid fuel burn is in the same direction as the airflow. The dynamics of solid fuel burn can be influenced by other parameters such as the spatial and temporal characteristics of the surface temperature, and the extent to which vaporized drug is redeposited on the substrate and/or other surfaces such as a housing in which the drug supply unit is incorporated.
  • [0200]
    In certain embodiments, thin film drug supply unit 500 can comprise more than one igniter 520 and/or each igniter 520 can comprise more than one initiator composition 522.
  • [0201]
    In certain embodiments, it can be useful to minimize the amount of initiator composition used, so as to reduce the amount of gas and other reaction products potentially generated by the initiator composition during burn.
  • [0202]
    In certain embodiments, igniter 520 can comprise a mechanism configured to direct transmitted radiation to an initiator composition capable of absorbing and being heated by the transmitted radiation, to produce sparks. For example, in certain embodiments, the radiation can be infrared, visible, or ultraviolet radiation such as produced by a diode laser, light emitting diode, or flashlamp. Radiation produced by a radiation source can be transmitted through a waveguide such as an optical fiber, and directed to an initiator or the radiation source can be incorporated into the ignition assembly 522 with electrical conductors for connecting to an external power source. The transmission device can include elements such as lenses for focusing the transmitted radiation onto the initiator composition. In certain embodiments, the radiation can be directed to an initiator composition disposed within the heating unit through a window. The transmitted radiation can be directed onto an absorber or a material capable of absorbing the radiation, which can be the initiator composition, or an element on which the initiator composition is disposed. In certain embodiments, the initiator composition can comprise at least one metal such as, but not limited to, zirconium, titanium, or aluminum, and at least one solid oxidizer such as, but not limited to, MoO3, KClO4, CuO, or WO3. The initiator composition can comprise any of those disclosed herein.
  • [0203]
    As shown in FIG. 10A, thin film drug supply unit 500 can have a spacer 518. Spacer 518 can retain igniter 520. In certain embodiments, spacer 518 can provide a volume or space within the interior of thin film heating unit 500 to collect gases and byproducts generated during the burn of the initiator composition 522 and solid fuel 512. The volume produced by spacer 518 can reduce the internal pressure within thin film drug supply unit 500 upon ignition of the fuel. In certain embodiments, the volume can comprise a porous or fibrous material such as a ceramic, or fiber mat in which the solid matrix component is a small fraction of the unfilled volume. The porous or fibrous material can provide a high surface area on which reaction products generated during the burning of the initiator composition and the solid fuel can be absorbed, adsorbed or reacted. The pressure produced during burn can in part depend on the composition and amount of initiator composition and solid fuel used. In certain embodiments, the spacer can be less than 0.3 inches thick, and in certain embodiments less than 0.2 inches thick. In certain embodiments, the maximum internal pressure during and following burn can be less than 50 psig, in certain embodiments less than 20 psig, in certain embodiments less than 10 psig, and in other certain embodiments less than 6 psig. In certain embodiments, the spacer can be a material capable of maintaining structural and chemical properties at the temperatures produced by the solid fuel burn. In certain embodiments, the spacer can be a material capable of maintaining structure and chemical properties up to a temperature of about 100° C. It can be useful that the material forming the spacer not produce and/or release or produce only a minimal amount of gases and/or reaction products at the temperatures to which it is exposed by the heating unit. In certain embodiments, spacer 518 can comprise a metal, a thermoplastic, such as, for example, but not limitation, a polyimide, fluoropolymer, polyetherimide, polyether ketone, polyether sulfone, polycarbonate, other high temperature resistant thermoplastic polymers, or a thermoset, and which can optionally include a filler.
  • [0204]
    In certain embodiments, spacer 518 can comprise a thermal insulator such that the spacer does not contribute to the thermal mass of the thin film drug supply unit thereby facilitating heat transfer to the substrate on which drug 514 is disposed. Thermal insulators or impulse absorbing materials such as mats of glass, silica, ceramic, carbon, or high temperature resistant polymer fibers can be used. In certain embodiments, spacer 518 can be a thermal conductor such that the spacer functions as a thermal shunt to control the temperature of the substrate.
  • [0205]
    Substrates 510, spacer 518 and igniter 520 can be sealed. Sealing can retain any reactants and reaction products released by burning of initiator composition 522 and solid fuel 514, as well as provide a self-contained unit. As shown in FIG. 10A, substrates 510 can be sealed to spacer 518 using an adhesive 516. Adhesive 516 can be a heat sensitive film capable of bonding substrates 510 and spacer 518 upon the application of heat and pressure. In certain embodiments, substrates 510 and spacer 518 can be bonded using an adhesive applied to at least one of the surfaces to be bonded, the parts assembled, and the adhesive cured. The access in spacer 518 into which igniter 520 is inserted can also be sealed using an adhesive. In certain embodiments, other methods for forming a seal can be used such as for example, welding, soldering, or fastening.
  • [0206]
    In certain embodiments, the elements forming the thin film drug supply unit 500 can be assembled and sealed using thermoplastic or thermoset molding methods such as insert molding and transfer molding.
  • [0207]
    An appropriate sealing method can, at least in part be determined by the materials forming substrate 510 and spacer 518. In certain embodiments, drug supply unit 500 can be sealed to withstand a maximum pressure of less than 50 psig. In certain embodiments less than 20 psig, and in certain embodiments less than 10 psig. In certain embodiments, the materials used to form the seal can maintain structural integrity at the temperature reached by the article. In certain embodiments, the materials used can exhibit minimal degradation and produce minimal gaseous reaction products at the temperature reached by the heating unit.
  • MULTIDOSE DRUG SUPPLY UNITS
  • [0208]
    In certain embodiments, a drug supply unit can be configured for use in single-use devices or in multi-use devices. FIGS. 9A-9B illustrate certain embodiments of drug supply units configured for use in a drug delivery device designed for multiple uses. As shown in FIG. 9A, a tape 406 in the form of a spool or reel 400 comprises a plurality of drug supply units 402, 404. The plurality of drug supply units 402, 404 can comprise a heating unit on which is disposed a thin film of a drug to be thermally vaporized. Each of the plurality of drug supply units 402, 404 can comprise the same features as those described herein, for example, in FIG. 1A and/or FIG. 1B. In certain embodiments, tape 406 can comprise a plurality of heating units. Each heating unit can comprise a solid fuel, an initiator composition, and a substrate.
  • [0209]
    Embodiments of thin film drug supply units are schematically illustrated in FIGS. 11A-11B. FIGS. 11A-11B illustrate certain embodiments wherein the thin film drug supply units 600 are in the form of a tape 650 comprising multiple layers. As shown in FIG. 11A, tape 650 comprises a first layer 601 having openings in which a drug to be thermally vaporized 610 is disposed. A second layer 602 underlying first layer 601 separates drug 610 from solid fuel 620 disposed within a third layer 603 underlying second layer 602. Second layer 602 can be thermally conductive such that heat can be efficiently transferred from solid fuel 620 to compound 610. In certain embodiments, second layer 602 can be any of the metals described herein. Regions comprising solid fuel 620 underlie regions comprising drug 610. The amount of solid fuel 620 can be an amount sufficient to thermally vaporize drug 610. The dimensions and geometry of the region comprising solid fuel 620 can be any appropriate dimension. In certain embodiments, third layer 603 can comprise a volume 640 to collect reaction products generated during burn of solid fuel 620 and thereby reduce the pressure within thin film drug supply unit 600. In certain embodiments (not shown), volume 640 can comprise a material capable of absorbing, adsorbing or reacting with reaction products produced during burning of the solid, such as a porous ceramic or fibrous material. Third layer 603 can comprise a material in which the mechanical properties are substantially maintained and which will not appreciably chemically degrade up to the temperatures reached by the drug supply unit 600. In certain embodiments, third layer 603 can comprise a metal or a polymer such as polyimide, fluoropolymer, polyetherimide, polyether ketone, polyether sulfone, polycarbonate, or other high temperature resistance polymers.
  • [0210]
    In certain embodiments, tape 650 can comprise an upper and lower layer (not shown) configured to physically and/or environmentally protect compound 610 and solid fuel 620. The upper and/or lower protective layers can comprise, for example, a metal foil, a polymer, or can comprise a multilayer comprising metal foil and polymers. In certain embodiments, protective layers can exhibit low permeability to oxygen, moisture, and/or corrosive gases. All or portions of a protective layer can be removed prior to use to expose compound 610 and solid fuel 620. To vaporize compound 610, solid fuel 620 can be ignited by energy from an external source (not shown) to generate heat that can be conducted through second layer 602 to thermally vaporize compound 610. Examples of initiators include those discussed herein such as, but not limited to, sparks or electrical resistance heating. Use of a protective layer can facilitate use of drug 610 in the form of a powder or liquid.
  • [0211]
    [0211]FIG. 11B shows a cross-sectional view of a tape 670 comprising thin film drug supply units 600, which in addition to the elements recited for FIG. 11A, further comprise an initiator composition 630. Tape 670 has multiple layers including first layer 601 within which compound 610 is disposed, second layer 602 separating first layer 601 and third layer 603. Layer 603 retains solid fuel 620 and in certain embodiments, a volume 640. Openings in a fourth layer 604 define a gap separating solid fuel 620 disposed in third layer 603, and initiator composition 630 disposed within regions of a fifth layer 605. Initiator composition 630 can comprise any of the initiator compositions disclosed herein. Initiator 630 can adjoin an electrically resistive heating element 682 disposed within a sixth layer 606 and connected to electrical conductors 680 also disposed within sixth layer 606. As shown, a seventh layer 607 overlies sixth layer 606 and comprises openings 617 to facilitate electrical connection between electrical conductors 680 and a power source (not shown).
  • [0212]
    In an exemplary operation, tape 670 can be advanced to locate at least one region comprising drug 610 within an airway (not shown) and to connect respective electrical contacts 680, with a power source (not shown). Upon activation of the power source, the electrical current can heat resistive element 682 to ignite initiator composition 630 and produce sparks. Sparks directed across gap 645 can ignite solid fuel 620. Heat generated by the ignition of solid fuel 620 can be conducted through second layer 602 thermally vaporizing compound 610 to form an aerosol comprising drug 610 within the airway.
  • [0213]
    Certain embodiments of another drug supply article configured for the delivery of multiple doses is illustrated in FIG. 9B. FIG. 9B shows a plurality of individual drug-supply units provided on a card 410. Drug supply units 412, 414, 416, each consist of a solid fuel contained between a backing member and a substrate, such as substrate 418 on unit 412. A film of drug can be coated onto substrate 418. Card 410 can be loaded into a suitable device configured to ignite at least one drug supply unit at a time. Ignition can be, for example by sparks, as disclosed herein. To provide a subsequent dose, card 410 can be rotated to advance a fresh drug supply unit.
  • [0214]
    [0214]FIG. 9C shows a cartridge 420 containing a plurality of cylindrically-shaped drug supply units 422, 424, 426, 428. The drug supply units can be as described herein, and comprise a solid fuel contained within an enclosure comprising a substrate. The external surface of the substrate can be coated with a film of drug. Each drug supply unit can be successively advanced into position in a drug delivery device chamber for ignition of the solid fuel, vaporization of the drug, and administration to a user.
  • DRUG DELIVERY DEVICES
  • [0215]
    Certain embodiments include drug delivery devices comprising a housing defining an airway, a heating unit as disclosed herein, a drug disposed on a portion of the exterior surface of a substrate of the heating unit, wherein the portion of the exterior surface comprising the drug is configured to be disposed within the airway, and an initiator configured to ignite the solid fuel. Drug delivery devices can incorporate the heating units and drug supply units disclosed herein. The drug delivery device can comprise a housing defining an airway. The housing can define an airway having any appropriate shape or dimensions and can comprise at least one inlet and at least one outlet. The dimensions of an airway can at least in part be determined by the volume of air that can be inhaled through the mouth or the nostrils by a user in a single inhalation, the intended rate of airflow through the airway, and/or the intended airflow velocity at the surface of the substrate that is coupled to the airway and on which a drug is disposed. In certain embodiments, airflow can be generated by a patient inhaling with the mouth on the outlet of the airway, and/or by inhaling with the nostrils on the outlet of the airway. In certain embodiments, airflow can be generated by injecting air or a gas into the inlet such as for example, by mechanically compressing a flexible container filled with air and/or gas, or by releasing pressurized air and/or gas into the inlet of the airway. Generating an airflow by injecting air and/or gas into the airway can be useful in drug delivery devices intended for topical administration of an aerosol comprising a drug.
  • [0216]
    In certain embodiments, a housing can be dimensioned to provide an airflow velocity through the airway sufficient to produce an aerosol of a drug during thermal vaporization. In certain embodiments, the airflow velocity can be at least 1 m/sec in the vicinity of the substrate on which the drug is disposed.
  • [0217]
    In certain embodiments, a housing can be dimensioned to provide a certain airflow rate through the airway. In certain embodiments, the airflow rate through the airway can range from 10 L/min to 120 L/min. In certain embodiments, an airflow rate ranging from 10 L/min to 120 L/min can be produced during inhalation by a user when the outlet exhibits a cross-sectional area ranging from 0.1 cm2 to 20 cm2. In certain embodiments, the cross-sectional area of the outlet can range from 0.5 cm2 to 5 cm2, and in certain embodiments, from 1 cm2 to 2 cm2.
  • [0218]
    In certain embodiments, an airway can comprise one or more airflow control valves to control the airflow rate and airflow velocity in airway. In certain embodiments, an airflow control valve can comprise, but is not limited to, at least one valve such as an umbrella valve, a reed valve, a flapper valve, or a flapping valve that bends in response to a pressure differential, and the like. In certain embodiments, an airflow control valve can be located at the outlet of the airway, at the inlet of the airway, within the airway, and/or can be incorporated into the walls of housing defining the airway. In certain embodiments, an airflow control valve can be actively controlled, for example can be activated electronically such that a signal provided by a transducer located within the airway can control the position of the valve; or passively controlled, such as, for example, by a pressure differential between the airway and the exterior of the device.
  • [0219]
    Certain embodiments of drug delivery devices configured for inhalation delivery of thermal vapor generated from a drug supply unit are illustrated in FIG. 8. Inhalation device 150 has an upper external housing member 152 and a lower external housing member 154 that snap fit together. The downstream end of each housing member can be gently tapered for insertion into a user's mouth, as shown on upper housing member 152 at downstream end 156. The upstream end of the upper and lower housing members can be slotted 158, as shown in the upper housing member 152, to provide for air intake when a user inhales. When fitted together, upper and lower housing members 152, 154 define a chamber 160. A drug supply unit 162 can be positioned within chamber 160. Drug supply unit 162 comprises a tapered, substantially cylindrical substrate 164 having an external surface 168 on which is disposed a film 166 of drug. The interior surface 170 of the substrate and a portion of the inner, cylindrical backing member 172 are shown in the cut-away section of drug supply unit 162. Solid fuel 174 is located within the annular shell region defined by backing member 172 and interior substrate surface 170. At least one initiator composition can be provided for the heating unit, and in certain embodiments as shown in FIG. 8, an initiator composition can be positioned (not shown) in the upstream end of the device where the air intake occurs. The initiator composition can be configured to ignite solid fuel 174 by the application of electrical current to an ohmic heating element connected to a battery (not shown) located in end piece 176. Activation of the initiator composition can produce sparks that are confined within a space defined by backing member 172 and thus can be directed toward the downstream end of the drug supply unit indicated at point 178. Sparks reaching the tapered nose portion at downstream end 178 can ignite solid fuel 174. Solid fuel 174 then burns in a downstream-to-upstream direction, i.e. from point 178 toward the air intake end of the device at point 158, generating a wave of heat in the downstream-to-upstream direction that vaporizes drug film 166 disposed on exterior substrate surface 168. Thus, the direction of solid fuel burn and the direction of thermal drug vapor generation are opposite the direction of airflow through chamber 160 of the inhalation device.
  • METHODS FOR PRODUCING AND USING AEROSOLS
  • [0220]
    Certain embodiments include methods of producing an aerosol of a compound using the heating units, drug supply units, and drug delivery devices disclosed herein. In certain embodiments, the aerosol produced by an apparatus can comprise a therapeutically effective amount of a drug. The temporal and spatial characteristics of the heat applied to thermally vaporize the compound disposed on the substrate and the air flow rate can be selected to produce an aerosol comprising a drug having certain characteristics. For example, for intrapulmonary delivery it is known that aerosol particles having a mean mass aerodynamic diameter ranging from 0.01 μm to 0.1 μm and ranging from 1 μm to 3.5 μm can facilitate efficient transfer of drugs from alveoli to the systemic circulation. In applications wherein the aerosol is applied topically, the aerosol can have the same or different characteristics.
  • [0221]
    Certain embodiments include methods for producing an aerosol comprising: (i) providing an airflow over a drug disposed on a portion of an exterior surface of a substrate forming a drug supply unit, wherein the drug supply unit comprises a heating unit as disclosed herein and the drug disposed on a portion of the exterior surface of the substrate, wherein the portion of the exterior surface comprising the drug is disposed within the airway; and an initiator composition configured to ignite the solid chemical fuel; and (ii) thermally vaporizing and condensing the drug to form an aerosol of the drug in the airway. In certain embodiments, the drug is disposed on the surface of the substrate as a thin film.
  • [0222]
    Certain embodiments include methods of treating a disease in a patient in need of such treatment comprising administering to the patient an aerosol comprising a therapeutically effective amount of a drug, wherein the aerosol is produced by the methods and devices disclosed herein. The aerosol can be administered by inhalation through the mouth, by nasal ingestion, and/or by topical application.
  • [0223]
    Other embodiments will be apparent to those skilled in the art from consideration and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only.
  • EXAMPLES
  • [0224]
    In the examples below, the following abbreviations have the following meanings. If an abbreviation is not defined, it has its generally accepted meaning.
  • [0225]
    wt % weight percent
  • [0226]
    psig pounds per square inch, gauge
  • [0227]
    DI deionized
  • [0228]
    mL milliliters
  • [0229]
    msec milliseconds
  • [0230]
    L/min liters per minute
  • [0231]
    μm micrometer
  • Example 1 Preparation of Solid Fuel with Laponite
  • [0232]
    The following procedure was used to prepare solid fuel coatings comprising 76.16% Zr: 19.04% MoO3: 4.8% Laponite® RDS.
  • [0233]
    To prepare wet Zirconium (Zr), the as-obtained suspension of Zr in DI water (Chemetall, Germany) was agitated on a roto-mixer for 30 minutes. Ten to 40 mL of the wet Zr was dispensed into a 50 mL centrifuge tube and centrifuged (Sorvall 6200RT) for 30 minutes at 3,200 rpm. The DI water was removed to leave a wet Zr pellet.
  • [0234]
    To prepare a 15% Laponite® RDS solution, 85 grams of DI water was added to a beaker. While stirring, 15 grams of Laponite® RDS (Southern Clay Products, Gonzalez, Tex.) was added, and the suspension stirred for 30 minutes.
  • [0235]
    The reactant slurry was prepared by first removing the wet Zr pellet as previously prepared from the centrifuge tube and placed in a beaker. Upon weighing the wet Zr pellet, the weight of dry Zr was determined from the following equation:
  • Dry Zr (g)=0.8234 (Wet Zr (g))−0.1059.
  • [0236]
    The amount of molybdenum trioxide to provide a 80:20 ratio of Zr to MoO3 was then determined, e.g, MoO3=Dry Zr (g)/4, and the appropriate amount of MoO3 powder (Accumet, N.Y.) was added to the beaker containing the wet Zr to produce a wet Zr: MoO3 slurry. The amount of Laponite® RDS to obtain a final weight percent ratio of dry components of 76.16% Zr: 19.04% MoO3: 4.80% Laponite® RDS was determined. Excess water to obtain a reactant slurry comprising 40% DI water was added to the wet Zr and MoO3 slurry. The reactant slurry was mixed for 5 minutes using an IKA Ultra-Turrax mixing motor with a S25N-8G dispersing head (setting 4). The amount of 15% Laponite® RDS previously determined was then added to the reactant slurry, and mixed for an additional 5 minutes using the IKA Ultra-Turrax mixer. The reactant slurry was transferred to a syringe and stored for at least 30 minutes prior to coating.
  • [0237]
    The Zr: MoO3: Laponite® RDS reactant slurry was then coated onto stainless steel foils. Stainless steel foils were first cleaned by sonication for 5 minutes in a 3.2% bv solution of Ridoline 298 in DI water at 60° C. Stainless steel foils were masked with 0.215 inch wide Mylar® such that the center portion of each 0.004 inch thick 304 stainless steel foil was exposed. The foils were placed on a vacuum chuck having 0.008 inch thick shims at the edges. Two (2) mL of the reactant slurry was placed at one edge of the foil. Using a Sheen Auto-Draw Automatic Film Applicator 1137 (Sheen Instruments) the reactant slurry was coated onto the foils by drawing a #12 coating rod at an auto-draw coating speed of up to 50 mm/sec across the surface of the foils to deposit approximately an 0.006 inch thick layer of the Zr: MoO3: Laponite® RDS reactant slurry. The coated foils were then placed in a 40° C. forced-air convection oven and dried for at least 2 hours. The masks were then removed from the foils to leave a coating of solid fuel on the center section of each foil.
  • [0238]
    The solid fuel coatings comprising Laponite® RDS adhered to the stainless steel foil surface and maintained physical integrity following mechanical and environmental testing including temperature cycling (−25° C.
    Figure US20040234699A1-20041125-P00900
    40° C.), accelerated humidity exposure (40° C./75% RH), drop testing, impact testing, and flexure testing.
  • Example 2 Measurement of Internal Pressure
  • [0239]
    Thin film heating units were used to measure the peak internal pressure and the peak temperature of the exterior surface of the substrate following ignition of the solid fuel.
  • [0240]
    The thin film heating units were substantially as described in Example 9 below and as illustrated in FIGS. 10A and 10B. Two, 2×2 square inch, 0.004 inch thick 304 stainless steel foils formed the substrates. A solid fuel comprising 76.16 wt % Zr, 19.04% MoO3, 4.8% Laponite® RDS and water was coated onto the interior surface of the stainless steel substrates. The thickness of the solid fuel layer was 0.0018±0.0003 inches. The layer of solid fuel covered an area of 1.69 in2 and after drying, the weight of the solid fuel disposed on the interior surface of each substrate was 0.165 to 0.190 grams. The spacer comprised a 0.24 inch thick section of polycarbonate (Makrolon). The ignition assembly comprised a FR-4 printed circuit board having a 0.03 inch diameter opening at the end to be disposed within an enclosure defined by the spacer and the substrates. A 0.0008 inch diameter Nichrome wire was soldered to electrical conductors on the printed circuit board and positioned across the opening. An initiator composition comprising 26.5% Al, 51.4% MoO3, 7.7% B and 14.3% Viton A500 weight percent was deposited onto the Nichrome wire and dried.
  • [0241]
    To assemble the thin film drug supply unit, the Nichrome wire comprising the initiator composition was positioned at one end of the solid fuel area. A bead of epoxy (Epo-Tek 353 ND, Epoxy Technology) was applied to both surfaces of the spacer, and the spacer, substrates and the ignition assembly positioned and compressed. The epoxy was cured at a temperature of 100° C. for 3 hours.
  • [0242]
    To ignite the solid fuel, a 0.4 amp current was applied to the electrical conductors connected to the Nichrome wire.
  • [0243]
    The peak internal pressure was measured using a pressure sensor (Motorola, MPXA4250A) The external surface temperature was measured using IR camera (FLIR, Therma CAM SC3000).
  • Example 3 Thermal Images of Heating Unit
  • [0244]
    A solid fuel consisting of a mixture of zirconium (40.6 wt %), MoO3 (21.9 wt %), and KClO3 (1.9 wt %), nitrocellulose (0.6 wt %), and diatomaceous earth (35 wt %) was prepared. The solid fuel was placed in a 0.030-inch gap between a stainless steel substrate (0.015 inch wall thickness) and a stainless steel backing member (0.015 inch wall thickness). The diameter of the substrate was {fraction (9/16)} inch. The fuel was ignited, and thermal images of the heating unit were taken as a function of time after ignition. The results are shown in FIGS. 4A-4F.
  • Example 4 Thermal Images of Heating Units to Evaluate Surface Temperature Uniformity
  • [0245]
    A. A solid fuel consisting of a mixture of zirconium (53.8 wt %), MoO3 (23.1 wt %), and KClO3 (2.3 wt %), nitrocellulose (0.8 wt %) and diatomaceous earth (20 wt %), was prepared. The solid fuel mixture was placed in a 0.030-inch gap between a stainless steel substrate (0.015 inch wall thickness) and a stainless steel backing member (0.015 inch wall thickness). The diameter of the substrate was {fraction (9/16)} inch. The fuel was ignited, and a thermal image of the heating unit was taken 400 milliseconds after ignition. The image is shown in FIG. 5A.
  • [0246]
    B. A solid fuel consisting of a mixture of zirconium (46.9 wt %), MoO3 (25.2 wt %), KClO3 (2.2 wt %), nitrocellulose (0.7 wt %), and diatomaceous earth (25.0 wt %) was prepared. The solid fuel was placed in a 0.030-inch gap between a stainless steel substrate (0.015 inch wall thickness) and a stainless steel backing member (0.015 inch wall thickness). The diameter of the substrate was {fraction (9/16)} inch. The fuel was ignited, and a thermal image of the heating unit was taken 400 milliseconds after ignition. The image is shown in FIG. 5B.
  • Example 5 Exemplary Heating Unit
  • [0247]
    A solid fuel consisting of a mixture of zirconium (46.9 wt %), MoO3 (25.2 wt %), and KClO3 (2.2 wt %), grain size 100-325 mesh, along with nitrocellulose (0.7 wt %) and diatomaceous earth (25.0 wt %) was prepared. The solid fuel was placed in a 0.030-inch gap between a stainless steel substrate (0.015 inch wall thickness) and a stainless steel backing member (0.015 inch wall thickness). The diameter of the substrate was {fraction (9/16)} inch. The solid fuel was remotely ignited from the tip of the heating unit. During and after burn, the pressure in the cylindrical substrate was measured as described herein. The burn propagation speed and the surface temperature uniformity were evaluated by infrared imaging.
  • [0248]
    The internal pressure increased to 150 psig during the reaction period of 0.3 seconds. The residual pressure was under 60 psig. The burn propagation speed was 13 cm/sec. With respect to surface temperature uniformity, no obvious cold spots were observed.
  • Example 6 Heating Unit Embodiment
  • [0249]
    A solid fuel consisting of a mixture of zirconium (69.3 wt %) and MoO3 (29.7 wt %), grain size 100-325 mesh, along with nitrocellulose (1.0 wt %) was prepared. The solid fuel mixture was placed in a 0.020-inch gap between a stainless steel substrate (0.020 inch wall thickness) and a stainless steel backing member (0.020 inch wall thickness). The outside of the backing member was coated with initiator to increase burn propagation speed. The primary fuel was remotely ignited from the tip of the heating unit. During and after burn, the pressure in the cylindrical substrate was measured as described herein. The burn propagation speed and the surface temperature uniformity were evaluated by infrared imaging.
  • [0250]
    The internal pressure increased to 200 psig during the reaction period of 0.25 seconds. The residual pressure was under 60 psig. The burn propagation speed was 15 cm/sec. With respect to surface temperature uniformity, no obvious cold spots were observed.
  • Example 7 Heating Unit Embodiment
  • [0251]
    A solid fuel consisting of a mixture of aluminum (49.5 wt %) and MoO3 (49.5 wt %), grain size 100-325 mesh, along with nitrocellulose (1.0 wt %) was prepared. The solid fuel mixture was placed in a 0.020-inch gap between a stainless steel substrate (0.020 inch wall thickness) and a stainless steel backing member (0.020 inch wall thickness). The primary fuel was directly ignited near the plug. During and after burn, the pressure in the cylindrical substrate was measured as described herein. The surface temperature uniformity was evaluated by infrared imaging.
  • [0252]
    The internal pressure increased to 300 psig during the reaction period of less than 5 milliseconds. The residual pressure was under 60 psig. The exterior surface expanse was uniformly heated, with between 5-10 percent of the surface being 50° C. to 100° C. cooler than the rest of the expanse.
  • Example 8 Wet Processing for Zirconium Fuel Slurry
  • [0253]
    The following procedure was used to prepare fuel compositions comprising Zr and MoO3 for a thin film drug supply unit. Wet Zr particles, 46.7 wt %, having a 2 μm to 3 μm particle size were obtained from Chemetall, GmbH, Germany. The Zr particles were rinsed with DI water, following which the excess water was decanted. DI water, 5.1 wt %, was added to the Zr and the mixture centrifuged. Excess water was decanted. Dry MoO3, 20 wt %, (Climax Molybdenum Co., Ariz.) and DI water was then added to the washed Zr, and the mixture homogenized for 2 minutes with a high shear mixer (IKA, Germany). A 15% aqueous solution of Laponite® RDS, 2.5 wt %, (Southern Clay Products, Inc., Tex.) was added and the mixture homogenized with a high shear mixer for an additional 5 minutes. The Zr: MO3 solid fuel slurry was transferred to a syringe or holding vessel for subsequent coating. The wet Zr included 8.5 wt % water and the Laponite® RDS gel included 14 wt % water. The weight percents represent the percent weight of the total wet composition.
  • Example 9 Thin Film Drug Supply Unit Embodiment
  • [0254]
    A thin film drug supply unit according to FIGS. 10A-10B was fabricated and the performance evaluated. Two, 2×2 square inch, 0.004 inch thick 304 stainless steel foils formed the substrates. A solid fuel comprising 76.16 wt % Zr and 19.04% MoO3 and 4.8% Laponite® RDS and water was coated onto the interior surface of the stainless steel substrates. The thickness of the solid fuel layer was 0.0018±0.0003 inches. The layer of solid fuel covered an area of 1.69 in2 and after drying, the weight of the solid fuel disposed on the interior surface of each substrate was 0.165 to 0.190 grams. An ˜6 μm thick thin film of a drug was deposited onto a 1.21 in2 area of the exterior substrate surfaces using spray coating. The drug was dissolved in a 15 mg/ml solution of isopropanol or acetone to facilitate processing. The thin film of drug was dried at ambient conditions and 1.5 mg to 3.0 mg of drug was deposited on the exterior surface of each substrate. The spacer comprised a 0.24 inch thick section of polycarbonate (Makronlon). The ignition assembly comprised a FR-4 printed circuit board having a 0.03 inch diameter opening at the end to be disposed within an enclosure defined by the spacer and the substrates. A 0.0008 inch diameter Nichrome wire was soldered to electrical conductors on the printed circuit board and positioned across the opening. An initiator composition comprising 26.5% Al, 51.4% MoO3, 7.7% B and 14.3% Viton A500 weight percent was deposited onto the Nichrome wire and dried.
  • [0255]
    To assemble the thin film drug supply unit, the Nichrome wire comprising the initiator composition was positioned at one end of the solid fuel area. A bead of epoxy (Epo-Tek 353 ND, Epoxy Technology) was applied to both surfaces of the spacer, and the spacer, substrates and the ignition assembly positioned and compressed. The epoxy was cured at a temperature of 100° C. for 3 hours.
  • [0256]
    To ignite the solid fuel, a 0.4 Amp current was applied to the electrical conductors connected to the Nichrome wire.
  • [0257]
    The airflow in the airway used for the measurements ranged from 14 L/min to 28 L/min corresponding to an airflow velocity of 1.5 m/sec and 3 m/sec, respectively.
  • [0258]
    Measurements on such drug supply units demonstrated that the exterior surface of the substrate reached temperatures in excess of 400° C. in less than 150 milliseconds following activation of the initiator at which time the drug was completely thermally vaporized. The maximum pressure within the enclosure was less than 10 psig. In separate measurements, it was demonstrated that the enclosure was able to withstand a static pressure in excess of 60 psig at room temperature. The burn propagation speed across the expanse of solid fuel was measured to be 25 cm/sec. The particulates forming the aerosol comprised greater than 95% of the drug, and greater than 90% of the drug originally deposited on the substrates formed the aerosol.
  • Example 10 Measurement of Aerosol Purity and Yield
  • [0259]
    Drug supply units substantially as described in Example 9 and illustrated in FIGS. 10A and 10B were used to measure the percent yield and percent purity of aerosols.
  • [0260]
    Two, 2×2 square inch, 0.004 inch thick 304 stainless steel foils formed the substrates. A solid fuel comprising 76.16 wt % Zr, 19.04% MoO3, 4.8% Laponite® RDS and water was coated onto the interior surface of the stainless steel substrates. The thickness of the solid fuel layer was 0.0018±0.0003 inches. The layer of solid fuel covered an area of 1.69 in2 and after drying, the weight of the solid fuel disposed on the interior surface of each substrate was 0.165 to 0.190 grams. An ˜6 μm thick thin film of a drug was deposited onto a 1.21 in2 area of the exterior substrate surfaces using spray coating. The drug was dissolved in a 15 mg/ml solution of isopropanol or acetone to facilitate processing. The thin film of drug was dried at ambient conditions and 1.5 mg to 3.0 mg of drug was deposited on the exterior surface of each substrate. The spacer comprised a 0.24 inch thick section of polycarbonate (Makronlon). The ignition assembly comprised a FR-4 printed circuit board having a 0.03 inch diameter opening at the end to be disposed within an enclosure defined by the spacer and the substrates. A 0.0008 inch diameter Nichrome wire was soldered to electrical conductors on the printed circuit board and positioned across the opening. An initiator composition comprising 26.5% Al, 51.4% MoO3, 7.7% B and 14.3% Viton A500 weight percent was deposited onto the Nichrome wire and dried.
  • [0261]
    To assemble the thin film drug supply unit, the Nichrome wire comprising the initiator composition was positioned at one end of the solid fuel area. A bead of epoxy (Epo-Tek 353 ND, Epoxy Technology) was applied to both surfaces of the spacer, and the spacer, substrates and the ignition assembly positioned and compressed. The epoxy was cured at a temperature of 100° C. for 3 hours.
  • [0262]
    To ignite the solid fuel, a 0.4 Amp current was applied to the electrical conductors connected to the Nichrome wire.
  • [0263]
    The airflow in the airway used for the measurements ranged from 14 L/min to 28 L/min corresponding to an airflow velocity of 1.5 m/sec and 3 m/sec, respectively.
  • [0264]
    After volatilization, the aerosol was captured on a mat for quantification of yield and analysis of purity. The quantity of material recovered on the mat was used to determine a percent yield, based on the mass of drug coated onto the substrate. Any material deposited on the housing or the remaining on the substrate was also recovered and quantified to determine a percent total recovery ((mass of drug on the mat+mass of drug remaining on substrate and housing)/mass of drug coated onto substrate). For compounds without UV absorption GC/MS or LC/MS was used to quantify the recovery.
  • [0265]
    The percent purity was determined using HPLC UV absorption at 250 nm. However, as one of skill in the art recognizes, the purity of a drug-containing aerosol may be determined using a number of different methods. It should be noted that when the term “purity” is used, it refers to the percentage of aerosol minus the percent byproduct produced in its formation. Byproducts for example, are those unwanted products produced during vaporization. For example, byproducts include thermal degradation products as well as any unwanted metabolites of the active compound or compounds. Examples of suitable methods for determining aerosol purity are described in Sekine et al., Journal of Forensic Science 32:1271-1280 (1987) and in Martin et al., Journal of Analytic Toxicology 13:158-162 (1989).
  • [0266]
    [0266]
  • [0267]
    One suitable method involves the use of a trap. In this method, the aerosol is collected in a trap in order to determine the percent or fraction of byproduct. Any suitable trap may be used. Suitable traps include mats, glass wool, impingers, solvent traps, cold traps, and the like. Mats are often most desirable. The trap is then typically extracted with a solvent, e.g. acetonitrile, and the extract subjected to analysis by any of a variety of analytical methods known in the art, for example, gas, liquid, and high performance liquid chromatography particularly useful.
  • [0268]
    The gas or liquid chromatography method typically includes a detector system, such as a mass spectrometry detector or an ultraviolet absorption detector. Ideally, the detector system allows determination of the quantity of the components of the drug composition and of the byproduct, by weight. This is achieved in practice by measuring the signal obtained upon analysis of one or more known mass(es) of components of the drug composition or byproduct (standards) and then comparing the signal obtained upon analysis of the aerosol to that obtained upon analysis of the standard(s), an approach well known in the art.
  • [0269]
    In many cases, the structure of a byproduct may not be known or a standard for it may not be available. In such cases, one may calculate the weight fraction of the byproduct by assuming it has an identical response coefficient (e.g. for ultraviolet absorption detection, identical extinction coefficient) to the drug component or components in the drug composition. When conducting such analysis, byproducts present in less than a very small fraction of the drug compound, e.g. less than 0.1% or 0.03% of the drug compound, are typically excluded. Because of the frequent necessity to assume an identical response coefficient between drug and byproduct in calculating a weight percentage of byproduct, it is often more desirable to use an analytical approach in which such an assumption has a high probability of validity. In this respect, high performance liquid chromatography with detection by absorption of ultraviolet light at 225 nm is typically desirable. UV absorption at 250 nm may be used for detection of compounds in cases where the compound absorbs more strongly at 250 nm or for other reasons one skilled in the art would consider detection at 250 nm the most appropriate means of estimating purity by weight using HPLC analysis. In certain cases where analysis of the drug by UV are not viable, other analytical tools such as GC/MS or LC/MS may be used to determine purity.
  • [0270]
    Although the invention has been described with respect to particular embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the invention.

Claims (40)

    What is claimed is:
  1. 1. A method of controlling uniformity of temperature and peak temperature of an exterior surface of a rapidly heated substrate comprising coating a thin layer of an essentially homogenous slurry of a selected mass of a solid fuel, which comprises an metal-containing oxidizing agent and a reducing agent in a defined ratio, on a portion of an interior surface of the substrate to be heated.
  2. 2. The method of claim 1, wherein said coating is a dip coating, spray coating, roller coating, gravure coating, reverse roll coating, gap coating, metering rod coating, slot die coating, curtain coating, and air knife coating.
  3. 3. The method of claim 2, wherein said gap coating is done with a wire wound coating rod.
  4. 4. The method of claim 1, wherein the peak temperature of the substrate upon heating is controlled by selecting and coating a mass of solid fuel determined to give that peak temperature.
  5. 5. The method of claim 1, wherein the substrate is selected from a metal, an alloy, and a ceramic.
  6. 6. The method claim 5, wherein the substrate is a metal foil.
  7. 7. The method of claim 6, wherein the metal foil exhibits a thickness ranging from 0.001 inches to 0.010 inches.
  8. 8. The method of claim 1, wherein the thin layer of solid fuel exhibits a thickness ranging from 0.001 inches to 0.030 inches.
  9. 9. The method of claim 1, wherein the thin layer of solid fuel exhibits a thickness ranging from 0.001 inches to 0.005 inches.
  10. 10. The method of claim 1, wherein the metal containing oxidizing agent is selected from at least one of the following MoO3, KClO4, KClO3, and Fe2O3.
  11. 11. The method of claim 1, wherein the metal reducing agent is selected form at least one of the following: aluminum, zirconium, iron, and titanium.
  12. 12. The heating unit of claim 1, wherein the amount of metal reducing agent ranges from 60% by weight to 90% by weight of the total dry weight of the solid fuel.
  13. 13. The heating unit of claim 1, wherein the amount of metal-containing oxidizing agent ranges from 10% by weight to 40% by weight of the total dry weight of the solid fuel.
  14. 14. The heating unit of claim 1, wherein the solid fuel comprises at least one additive material.
  15. 15. The method of claim 14, wherein said additive material is an inorganic material.
  16. 16. The method of claim 15, wherein the inorganic material is selected from the group consisting of clays, metal alkoxides, sodium silicates, potassium silicates, aluminum silicates, alumina, silica based sol and inorganic sol-gel material.
  17. 17. The method of claim 16, wherein the clay is selected from the group consisting of: Laponite, Montmorillonite, and Cloisite.
  18. 18. A method for providing an essentially homogenous and uniform coating of dry solid fuel on a surface of a substrate comprising:
    a. mixing a solid fuel, comprising at least one oxidizing agent and at least one reducing agent, with an additive material in a solvent to form a homogenous slurry;
    b. coating a thin layer of the slurry at a set thickness on an surface of a substrate; and
    c. drying the coated slurry to form a dry solid fuel on the substrate.
  19. 19. The method of claim 18, wherein said coating is dip coating, spray coating, roller coating, gravure coating, reverse roll coating, gap coating, metering rod coating, slot die coating, curtain coating, and air knife coating.
  20. 20. The method of claim 19, wherein said gap coating is done with a wire wound coating rod in a bar coater.
  21. 21. The method of claim 18, wherein prior to coating a mask is positioned on a portion of the surface of the substrate to prevent deposition of the solid fuel on said portion.
  22. 22. The method claim 18, wherein the substrate is a metal foil.
  23. 23. The method of claim 22, wherein the metal foil exhibits a thickness ranging from 0.001 inches to 0.010 inches.
  24. 24. The method of claim 18, wherein the thin layer of solid fuel exhibits a thickness ranging from 0.001 inches to 0.030 inches.
  25. 25. The method of claim 18, wherein the thin layer of solid fuel exhibits a thickness ranging from 0.001 inches to 0.005 inches.
  26. 26. The method of claim 18, wherein the metal containing oxidizing agent is selected from at least one of the following MoO3, KClO4, KClO3, and Fe2O3.
  27. 27. The method of claim 18, wherein the metal reducing agent is selected from at least one of the following: aluminum, zirconium, iron, and titanium.
  28. 28. The method of claim 18, wherein said additive material is an inorganic material.
  29. 29. The method of claim 18, wherein the additive material is Laponite.
  30. 30. The method of claim 18, wherein said drying is in an oven for at least two hours.
  31. 31. A heating unit that upon firing rapidly heats a defined area of an exterior surface of a substrate to an essentially uniform temperature and a set peak temperature comprising:
    a. an enclosure comprising at least one substrate having an exterior surface and an interior surface,
    b. an essentially homogenous and thin layer of solid fuel coated on the interior surface of the substrate corresponding to the defined area of the exterior surface of the substrate to be heated; and
    c. an igniter disposed within the enclosure for igniting the solid fuel.
  32. 32. The heating unit of claim 31, wherein the peak temperature is set by the mass of solid fuel coated on the interior surface of the substrate.
  33. 33. The method of claim 31, wherein the thin layer of solid fuel exhibits a thickness ranging from 0.001 inches to 0.030 inches.
  34. 34. The method of claim 31, wherein the thin layer of solid fuel exhibits a thickness ranging from 0.001 inches to 0.005 inches.
  35. 35. The method of claim 31, wherein the enclosure comprises more than one substrate.
  36. 36. The method of claim 31, wherein the substrate is a metal foil.
  37. 37. The method of claim 31, wherein the metal containing oxidizing agent is selected from at least one of the following MoO3, KClO4, KClO3, and Fe2O3.
  38. 38. The method of claim 31, wherein the metal reducing agent is selected from at least one of the following: aluminum, zirconium, iron, and titanium.
  39. 39. The method of claim 31, wherein the solid fuel comprises at least one additive material.
  40. 40. The method of claim 39, wherein the additive material is Laponite.
US10851429 2003-05-21 2004-05-20 Methods of controlling uniformity of substrate temperature and self-contained heating unit and drug-supply unit employing same Abandoned US20040234699A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US47269703 true 2003-05-21 2003-05-21
US10851429 US20040234699A1 (en) 2003-05-21 2004-05-20 Methods of controlling uniformity of substrate temperature and self-contained heating unit and drug-supply unit employing same

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10851429 US20040234699A1 (en) 2003-05-21 2004-05-20 Methods of controlling uniformity of substrate temperature and self-contained heating unit and drug-supply unit employing same
US12485704 US8387612B2 (en) 2003-05-21 2009-06-16 Self-contained heating unit and drug-supply unit employing same
US13783508 US8991387B2 (en) 2003-05-21 2013-03-04 Self-contained heating unit and drug-supply unit employing same
US14675275 US9370629B2 (en) 2003-05-21 2015-03-31 Self-contained heating unit and drug-supply unit employing same

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US10851883 Continuation-In-Part US20040234914A1 (en) 2003-05-21 2004-05-20 Percussively ignited or electrically ingnited self-contained heating unit and drug-supply unit employing same

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10850895 Continuation-In-Part US20050079166A1 (en) 2003-05-21 2004-05-20 Self-contained heating unit and drug-supply unit employing same
US12485704 Continuation-In-Part US8387612B2 (en) 2003-05-21 2009-06-16 Self-contained heating unit and drug-supply unit employing same

Publications (1)

Publication Number Publication Date
US20040234699A1 true true US20040234699A1 (en) 2004-11-25

Family

ID=33476972

Family Applications (7)

Application Number Title Priority Date Filing Date
US10851883 Abandoned US20040234914A1 (en) 2003-05-21 2004-05-20 Percussively ignited or electrically ingnited self-contained heating unit and drug-supply unit employing same
US10850895 Abandoned US20050079166A1 (en) 2003-05-21 2004-05-20 Self-contained heating unit and drug-supply unit employing same
US10851432 Abandoned US20040234916A1 (en) 2003-05-21 2004-05-20 Optically ignited or electrically ignited self-contained heating unit and drug-supply unit employing same
US10851429 Abandoned US20040234699A1 (en) 2003-05-21 2004-05-20 Methods of controlling uniformity of substrate temperature and self-contained heating unit and drug-supply unit employing same
US12485704 Active 2026-10-23 US8387612B2 (en) 2003-05-21 2009-06-16 Self-contained heating unit and drug-supply unit employing same
US13783508 Active US8991387B2 (en) 2003-05-21 2013-03-04 Self-contained heating unit and drug-supply unit employing same
US14675275 Active US9370629B2 (en) 2003-05-21 2015-03-31 Self-contained heating unit and drug-supply unit employing same

Family Applications Before (3)

Application Number Title Priority Date Filing Date
US10851883 Abandoned US20040234914A1 (en) 2003-05-21 2004-05-20 Percussively ignited or electrically ingnited self-contained heating unit and drug-supply unit employing same
US10850895 Abandoned US20050079166A1 (en) 2003-05-21 2004-05-20 Self-contained heating unit and drug-supply unit employing same
US10851432 Abandoned US20040234916A1 (en) 2003-05-21 2004-05-20 Optically ignited or electrically ignited self-contained heating unit and drug-supply unit employing same

Family Applications After (3)

Application Number Title Priority Date Filing Date
US12485704 Active 2026-10-23 US8387612B2 (en) 2003-05-21 2009-06-16 Self-contained heating unit and drug-supply unit employing same
US13783508 Active US8991387B2 (en) 2003-05-21 2013-03-04 Self-contained heating unit and drug-supply unit employing same
US14675275 Active US9370629B2 (en) 2003-05-21 2015-03-31 Self-contained heating unit and drug-supply unit employing same

Country Status (6)

Country Link
US (7) US20040234914A1 (en)
EP (5) EP1625333A1 (en)
JP (4) JP2007516404A (en)
CA (4) CA2526470A1 (en)
ES (1) ES2370395T3 (en)
WO (4) WO2004104490A9 (en)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060257329A1 (en) * 2001-05-24 2006-11-16 Alexza Pharmaceuticals, Inc. Delivery of drug esters through an inhalation route
US20070196666A1 (en) * 2005-07-11 2007-08-23 The Regents Of The University Of California Electrical initiation of an energetic nanolaminate film
US20080073558A1 (en) * 2006-09-25 2008-03-27 Philip Morris Usa Inc. Heat capacitor for capillary aerosol generator
US20090050355A1 (en) * 2007-08-24 2009-02-26 World Properties, Inc. Thermoplastic Films For Insulated Metal Substrates And Methods Of Manufacture Thereof
US7645442B2 (en) 2001-05-24 2010-01-12 Alexza Pharmaceuticals, Inc. Rapid-heating drug delivery article and method of use
US20100162913A1 (en) * 2006-05-18 2010-07-01 The Regents Of The University Of California Energetic composite and system with enhanced mechanical sensitivity to initiation of self-sustained reaction
US7834295B2 (en) 2008-09-16 2010-11-16 Alexza Pharmaceuticals, Inc. Printable igniters
US7913688B2 (en) 2002-11-27 2011-03-29 Alexza Pharmaceuticals, Inc. Inhalation device for producing a drug aerosol
US7923662B2 (en) 2004-05-20 2011-04-12 Alexza Pharmaceuticals, Inc. Stable initiator compositions and igniters
US7942147B2 (en) 2001-06-05 2011-05-17 Alexza Pharmaceuticals, Inc. Aerosol forming device for use in inhalation therapy
US7981401B2 (en) 2002-11-26 2011-07-19 Alexza Pharmaceuticals, Inc. Diuretic aerosols and methods of making and using them
US7987846B2 (en) 2002-05-13 2011-08-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US8003080B2 (en) 2002-05-13 2011-08-23 Alexza Pharmaceuticals, Inc. Delivery of drug amines through an inhalation route
US8235037B2 (en) 2001-05-24 2012-08-07 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US8288372B2 (en) 2002-11-26 2012-10-16 Alexza Pharmaceuticals, Inc. Method for treating headache with loxapine
US8333197B2 (en) 2004-06-03 2012-12-18 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
US8387612B2 (en) 2003-05-21 2013-03-05 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US8506935B2 (en) 2002-11-26 2013-08-13 Alexza Pharmaceuticals, Inc. Respiratory drug condensation aerosols and methods of making and using them
WO2013128176A1 (en) * 2012-02-28 2013-09-06 British American Tobacco (Investments) Limited Delivery devices and units therefor
US9063041B2 (en) 2012-11-30 2015-06-23 General Electric Company Device and method for drying biological sample on substrate
EP3049733A4 (en) * 2014-08-01 2017-03-22 Andrea Rossi Fluid heater
US9724341B2 (en) 2013-07-11 2017-08-08 Alexza Pharmaceuticals, Inc. Nicotine salt with meta-salicylic acid

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2641760A1 (en) * 2001-05-24 2002-11-28 Alexza Pharmaceuticals, Inc. Delivery of alprazolam, estazolam, midazolam or triazolam through an inhalation route
US7078016B2 (en) * 2001-11-21 2006-07-18 Alexza Pharmaceuticals, Inc. Delivery of caffeine through an inhalation route
US20060193788A1 (en) * 2002-11-26 2006-08-31 Hale Ron L Acute treatment of headache with phenothiazine antipsychotics
WO2004047841A1 (en) * 2002-11-26 2004-06-10 Alexza Molecular Delivery Corporation Treatment of headache with antipsychotics delivered by inhalation
WO2005118510A8 (en) * 2004-05-20 2006-02-23 Alexza Pharmaceuticals Inc Stable initiator compositions and igniters
CA2576961A1 (en) * 2004-08-12 2006-03-02 Alexza Pharmaceuticals, Inc. Aerosol drug delivery device incorporating percussively activated heat packages
JP2008509721A (en) * 2004-08-12 2008-04-03 アレックザ ファーマシューティカルズ, インコーポレイテッド Inhalation actuated impact ignition system
US20060209521A1 (en) * 2005-03-18 2006-09-21 Delta Electronics, Inc. Package structure for passive components and manufacturing method thereof
EP1912733B1 (en) * 2005-07-29 2012-05-16 SAES GETTERS S.p.A. Getter systems comprising a gas-sorbing phase in the pores of a porous material distributed in a permeable means
JP2009502472A (en) * 2005-07-29 2009-01-29 サエス ゲッタース ソチエタ ペル アツィオニ Getter system comprising an active phase that is inserted into the porous material is dispersed in a low permeability means
WO2007066372B1 (en) * 2005-12-06 2007-09-20 Getters Spa Electrolytic capacitors comprising means in the form of a multilayer polymeric sheet for the sorption of harmful substances
CN101313379B (en) * 2006-01-16 2012-07-11 工程吸气公司 Electrolytic capacitor comprising means for the sorption of harmful substances
US8092623B1 (en) * 2006-01-31 2012-01-10 The United States Of America As Represented By The Secretary Of The Navy Igniter composition, and related methods and devices
US9078294B2 (en) * 2006-08-07 2015-07-07 University Of Massachusetts Nanoheater elements, systems and methods of use thereof
FR2905882B1 (en) * 2006-09-14 2008-10-31 Saint Louis Inst Micro Manufacturing Process and / or nanothermites and nanothermites associated.
US7867441B2 (en) * 2006-12-05 2011-01-11 Lawrence Livermore National Security, Llc Low to moderate temperature nanolaminate heater
US20080299048A1 (en) * 2006-12-22 2008-12-04 Alexza Pharmaceuticals, Inc. Mixed drug aerosol compositions
DE102007023669B4 (en) * 2007-05-22 2010-12-02 Cosma Engineering Europe Ag Ignition device for explosive forming
FR2927233B1 (en) * 2008-02-08 2011-11-11 Oreal Device for applying a cosmetic product, comprising a heater member
US20100068155A1 (en) * 2008-09-16 2010-03-18 Alexza Pharmaceuticals, Inc. Reactant Formulations and Methods for Controlled Heating
US20100065052A1 (en) * 2008-09-16 2010-03-18 Alexza Pharmaceuticals, Inc. Heating Units
KR101600559B1 (en) * 2008-10-17 2016-03-08 엔씨씨 나노, 엘엘씨 Method for reducing thin films on low temperature substrates
US9055841B2 (en) * 2009-04-07 2015-06-16 Heatgenie, Inc. Package heating apparatus
US20100300433A1 (en) * 2009-05-28 2010-12-02 Alexza Pharmaceuticals, Inc. Substrates for Enhancing Purity or Yield of Compounds Forming a Condensation Aerosol
DE102010029007A1 (en) * 2010-05-17 2011-11-17 Robert Bosch Gmbh Means for determining a composition of a fuel mixture
US20120048963A1 (en) * 2010-08-26 2012-03-01 Alexza Pharmaceuticals, Inc. Heat Units Using a Solid Fuel Capable of Undergoing an Exothermic Metal Oxidation-Reduction Reaction Propagated without an Igniter
EP2756859B1 (en) * 2011-08-16 2016-09-21 PAX Labs, Inc. Low temperature electronic vaporization device
WO2015046387A1 (en) * 2013-09-30 2015-04-02 日本たばこ産業株式会社 Non-combusting flavor inhaler
US9549573B2 (en) 2013-12-23 2017-01-24 Pax Labs, Inc. Vaporization device systems and methods
US9380813B2 (en) 2014-02-11 2016-07-05 Timothy McCullough Drug delivery system and method
US9220294B2 (en) * 2014-02-11 2015-12-29 Timothy McCullough Methods and devices using cannabis vapors
CN104114050A (en) * 2014-05-30 2014-10-22 深圳市麦克韦尔科技有限公司 Electronic cigarette and atomizer
US9552711B2 (en) 2014-07-18 2017-01-24 Google Inc. Systems and methods for intelligent alarming
US9945560B1 (en) * 2015-03-29 2018-04-17 Paul Michael Rzonca Fire starter apparatus

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3830671A (en) * 1972-11-30 1974-08-20 American Metal Climax Inc Thermally ignitable zirconium-plastic composition
US4096549A (en) * 1976-11-09 1978-06-20 Gte Sylvania Incorporated Multilamp photoflash assembly
US4193388A (en) * 1978-04-19 1980-03-18 Nasa Portable heatable container
US5322018A (en) * 1991-11-27 1994-06-21 The Ensign-Bickford Company Surface-initiating deflagrating material
US6289889B1 (en) * 1999-07-12 2001-09-18 Tda Research, Inc. Self-heating flexible package
US6497780B1 (en) * 1999-06-09 2002-12-24 Steven A. Carlson Methods of preparing a microporous article
US6506454B2 (en) * 2000-03-07 2003-01-14 Koito Manufacturing Co., Ltd. Part painting method
US20030037437A1 (en) * 2001-05-08 2003-02-27 General Electric System for applying a diffusion aluminide coating on a selective area of a turbine engine component

Family Cites Families (624)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1803334A (en) 1931-05-05 Ootthujp lehmann
US2243669A (en) 1941-05-27 Electrical vaporizer
US3080624A (en) 1963-03-12 weber iii
US1864980A (en) 1932-06-28 Vapobizeb
US802256A (en) * 1904-07-13 1905-10-17 Max Bamberger Heating composition.
US1239634A (en) 1916-07-25 1917-09-11 Frank J Stuart Medical appliance.
US1535486A (en) 1922-08-28 1925-04-28 James W Lundy Electric-lamp bulb
DE561103C (en) 1928-01-07 1932-10-10 Wilhelm Rottgardt Muffle and use for inhalation, disinfecting apparatus o. The like.
DE571289C (en) 1931-11-22 1933-02-25 Otto Schmitt A process for the production of electrical igniters
US2024225A (en) * 1932-02-12 1935-12-17 Igari Mituyosi Flash light lamp
US2086140A (en) 1933-09-08 1937-07-06 Silten Ernst Automatic temperature regulated narcosis apparatus
US2084299A (en) 1934-12-15 1937-06-15 Arthur G Borden Medicament holder for nasal inhalers
US2104266A (en) 1935-09-23 1938-01-04 William J Mccormick Means for the production and inhalation of tobacco fumes
US2230754A (en) 1937-02-15 1941-02-04 Bilhuber Corp E Unsaturated ethylamine derivatives
US2230753A (en) 1937-02-15 1941-02-04 Bilhuber Corp E Unsaturated ethylamine derivatives
GB502761A (en) 1938-01-29 1939-03-24 Christopher Engelbreth Improvements in and relating to hand inhalation apparatus
US2285125A (en) * 1939-03-16 1942-06-02 Gen Electric Flash lamp
US2309846A (en) 1941-03-06 1943-02-02 Holm Einar Marius Inhaler
FR921852A (en) 1945-12-06 1947-05-21 Diffuser volatiles
US2500790A (en) * 1946-02-20 1950-03-14 Catalyst Research Corp Heating element
US2491416A (en) * 1946-04-03 1949-12-13 Fansteel Metallurgical Corp Tantalum oxide composition
US2469656A (en) 1946-04-19 1949-05-10 Peter H Lienert Vaporizer
US2531548A (en) * 1947-08-04 1950-11-28 Catalyst Research Corp Heating device
US2598823A (en) * 1947-12-04 1952-06-03 O'grady Austin Peter Joseph Inhalant preparation
US2624332A (en) * 1951-06-01 1953-01-06 Delmer T Lang Heating device
US2714649A (en) 1952-11-25 1955-08-02 Lyle H Critzer Vaporizer
US2761055A (en) 1953-06-10 1956-08-28 Malcome Van Ike Lamp-heated vaporizer
US3575714A (en) * 1953-08-07 1971-04-20 Catalyst Research Corp Thermal type primary cell
US2741812A (en) 1954-02-15 1956-04-17 Tellier Andre Perfume dispenser
US2906094A (en) * 1954-04-14 1959-09-29 Glenn H Damon Fuel and rapid ignition apparatus for ignition of fuel in ram jets and rockets
US2902484A (en) 1954-04-27 1959-09-01 Rhone Poulenc Sa Phenthiazine derivatives and processes for their preparation
US3884719A (en) * 1955-06-29 1975-05-20 Olin Mathieson Battery
US2887106A (en) 1956-09-27 1959-05-19 Robinson Joseph Combined vaporizer and cover for medicament jar
US2898649A (en) 1956-11-19 1959-08-11 Elaine T Cassidy Perfume diffuser
US2953443A (en) * 1957-02-11 1960-09-20 Alloyd Engineering Lab Inc Chemical heating composition, heating unit containing the same and method of manufacture
DE1163210B (en) 1959-03-02 Du Pont Electrical Safety Brueckenzuender
US3371085A (en) 1959-12-10 1968-02-27 Hoffmann La Roche 5-aryl-3h-1,4-benzodiazepin-2(1h)-ones
US3043977A (en) 1960-03-30 1962-07-10 Puritron Corp Device and method for producing negative ions
US3474101A (en) 1960-09-05 1969-10-21 Reckitt & Sons Ltd Thebaine and oripavine derivatives
FR1289468A (en) * 1960-12-08 1962-04-06 heater utilizing an exothermic chemical reaction
GB903866A (en) 1961-05-09 1962-08-22 Dausse Lab Therapeutic preparations containing 7-substituted theophylline derivatives
US3160097A (en) 1961-07-17 1964-12-08 Gen Precision Inc Molybdenum trioxide-aluminum explosive and exploding bridgewire detonator therefor
NL135583C (en) 1961-10-10
US3118798A (en) 1961-10-26 1964-01-21 Olin Mathieson Composition and method of forming
GB1001901A (en) * 1962-07-10 1965-08-18 Foseco Trading Ag Exothermic compositions
US3299185A (en) 1962-09-27 1967-01-17 Ube Nitto Kasei Co Dyeable polyolefin fibers containing a binary copolymer of styrene and acrylonitrile
US3169095A (en) 1962-10-30 1965-02-09 Rexall Drug Chemical Self-propelling powder-dispensing compositions
BE629985A (en) 1962-11-29
FR3384M (en) 1962-11-30 Benger Lab Ltd New composition for pharmaceutical aerosols.
GB1086861A (en) 1963-01-07 1967-10-11 Mini Of Technology Improvements in primary explosives
US3282729A (en) 1963-02-27 1966-11-01 Union Carbide Corp Barrier coated thermoplastic olefin polymer substrates
US3200819A (en) 1963-04-17 1965-08-17 Herbert A Gilbert Smokeless non-tobacco cigarette
NL298071A (en) 1963-06-04
US3150020A (en) 1963-10-29 1964-09-22 Earl E Kilmer Gasless igniter composition
US3311459A (en) * 1963-12-12 1967-03-28 Ontario Research Foundation Chemical heating device in sheet form
US4053337A (en) 1964-06-23 1977-10-11 Catalyst Research Corporation Heating composition
US4041217A (en) * 1964-06-23 1977-08-09 Catalyst Research Corporation Thermal battery with metal-metal oxide heating composition
FR1483505A (en) * 1965-06-19 1967-06-02 Agfa Gevaert Ag Installation for detecting auditory pathway by the noise in a room
US3425872A (en) * 1965-09-22 1969-02-04 Atomic Energy Commission Thermal battery having heat generating means comprising exothermically alloyable metals
US3363559A (en) 1965-10-04 1968-01-16 Estes Vernon Dale Resistance fuse wire
GB1119270A (en) 1966-01-19 1968-07-10 Endo Lab 14-hydroxy dihydronormorphine derivatives and their preparation
US3503814A (en) 1968-05-03 1970-03-31 Us Navy Pyrotechnic composition containing nickel and aluminum
US3535063A (en) * 1968-08-30 1970-10-20 Sylvania Electric Prod Photoflash lamp
US6487971B1 (en) * 1968-10-12 2002-12-03 The United States Of America As Represented By The Secretary Of The Navy Light initiated detonator
US3909463A (en) 1968-11-29 1975-09-30 Allied Chem Grafted block copolymers of synthetic rubbers and polyolefins
US3987052A (en) 1969-03-17 1976-10-19 The Upjohn Company 6-Phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines
US3703144A (en) 1969-09-16 1972-11-21 Space Ordnance Systems Inc Delay composition and device
US4008723A (en) 1970-03-23 1977-02-22 Imperial Chemical Industries Limited Smoking mixture
US3669748A (en) * 1970-06-08 1972-06-13 Dorothy H Spracklen Thermal battery
US3677822A (en) * 1970-10-23 1972-07-18 Atomic Energy Commission Thermal battery having a thermal reservoir pellet
US3695179A (en) 1970-11-24 1972-10-03 Westinghouse Electric Corp Electrically actuable ignitor for passenger restraint system employing an inflatable cushion
US3831606A (en) 1971-02-19 1974-08-27 Alza Corp Auto inhaler
US3749547A (en) 1971-09-09 1973-07-31 Airco Inc Flashlamp with improved combustible foil
US3847650A (en) 1971-09-09 1974-11-12 Airco Inc Flashlamp with improved combustion foil and method of making same
US3724990A (en) * 1971-11-15 1973-04-03 Gen Electric Photoflash lamp
US3724991A (en) * 1971-11-15 1973-04-03 Gen Electric Photoflash lamp
US4166087A (en) 1971-11-22 1979-08-28 Cline-Buckner, Inc. Automatic intermittent vapor dispenser
US3730669A (en) * 1971-12-23 1973-05-01 Gte Sylvania Inc Photographic flashlamp unit having control structure on base
US3701782A (en) 1972-02-10 1972-10-31 Upjohn Co 1-carbolower alkoxy - 6 - phenyl-4h-s-triazolo(1,4)benzodiazepine compounds
US3763347A (en) 1972-04-13 1973-10-02 Ncr Co Vaporous lamp
US3943941A (en) 1972-04-20 1976-03-16 Gallaher Limited Synthetic smoking product
USRE30285E (en) 1972-05-22 1980-05-27 Spraying devices, in particular nebulizing devices
US3864326A (en) 1972-05-22 1975-02-04 Robert S Babington Spraying devices, in particular nebulizing devices
GB1366041A (en) 1972-07-21 1974-09-11 Kodama Bros Co Ltd Device for volatilizing insecticides and the like
US3791302A (en) * 1972-11-10 1974-02-12 Leod I Mc Method and apparatus for indirect electrical ignition of combustible powders
US3893798A (en) * 1972-12-15 1975-07-08 Gen Electric Photoflash lamp
US3792302A (en) 1972-12-22 1974-02-12 Raytheon Co Vhf slow wave structure
US3828676A (en) 1973-01-18 1974-08-13 R Junker Consumable explosive cartridges
US3949743A (en) 1973-03-19 1976-04-13 Schick Incorporated Medicated vapor production method and apparatus
FR2234532B1 (en) * 1973-06-19 1976-04-30 Poudres & Explosifs Ste Nale
US3930796A (en) 1973-09-13 1976-01-06 Universal Oil Products Company Catalytic fume control device
US3982095A (en) 1973-10-04 1976-09-21 Searle Cardio-Pulmonary Systems Inc. Respiratory humidifier
US3971377A (en) 1974-06-10 1976-07-27 Alza Corporation Medicament dispensing process for inhalation therapy
US3894040A (en) 1974-09-16 1975-07-08 American Home Prod 2,5,6,7-Tetrahydro-3H-imidazo(1,2-D)(1,4)benzodiazepine-5,6-dicarboxylic acid esters
US4000022A (en) 1974-10-17 1976-12-28 The United States Of America As Represented By The Secretary Of The Navy Fast-burning compositions of fluorinated polymers and metal powders
US4045156A (en) 1974-12-23 1977-08-30 Gte Sylvania Incorporated Photoflash lamp
US4013061A (en) * 1975-01-29 1977-03-22 Thermology, Inc. Ignition system for chemical heaters
US4020379A (en) 1975-10-02 1977-04-26 Eg&G, Inc. Bulb-shaped flashtube with metal envelope
US4025285A (en) * 1975-10-28 1977-05-24 Gte Sylvania Incorporated Photoflash lamp
US4059388A (en) * 1975-11-05 1977-11-22 Gte Sylvania Incorporated Photoflash lamp
US4104210A (en) 1975-12-17 1978-08-01 Monsanto Company Thermoplastic compositions of high unsaturation diene rubber and polyolefin resin
US4047483A (en) * 1976-03-24 1977-09-13 The United States Of America As Represented By The Secretary Of The Army Initiator for use in laser beam ignition of solid propellants
US4121583A (en) 1976-07-13 1978-10-24 Wen Yuan Chen Method and apparatus for alleviating asthma attacks
US4286604A (en) 1976-10-05 1981-09-01 Gallaher Limited Smoking materials
US4079742A (en) 1976-10-20 1978-03-21 Philip Morris Incorporated Process for the manufacture of synthetic smoking materials
DE2648308C3 (en) * 1976-10-26 1979-08-30 Dynamit Nobel Ag, 5210 Troisdorf
US4160765A (en) 1976-11-17 1979-07-10 Smithkline Corporation Method for 6-bromination of 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine compounds
US4078881A (en) * 1976-12-16 1978-03-14 General Electric Company Photoflash lamp
US4141369A (en) 1977-01-24 1979-02-27 Burruss Robert P Noncombustion system for the utilization of tobacco and other smoking materials
US4158084A (en) * 1977-02-18 1979-06-12 The United States Of America As Represented By The Secretary Of The Navy Heat sources for thermal batteries: exothermic intermetallic reactions
US4184099A (en) 1977-04-27 1980-01-15 International Flavors & Fragrances Inc. Composition for slow release of volatile ingredients at _high temperature; and article comprising same
US4130082A (en) * 1977-06-06 1978-12-19 Gte Sylvania Incorporated Flashlamp assembly for providing highly intense audible and visual signals
DE2752384A1 (en) 1977-08-29 1979-03-15 Simes A pharmaceutical preparation based beklemmungsloesender agents and inhibitors of beta-adrenergic receptors
DE2851543A1 (en) 1977-12-01 1979-06-07 Welsh Nat School Med Inhalationspraeparat
US4183912A (en) 1978-01-16 1980-01-15 American Home Products Corporation Inhalation therapy for relieving bronchial spasm using quaternary salts of promethazine
JPS54120065A (en) 1978-02-24 1979-09-18 Osaka Takeshi Stick for blind person
US4198200A (en) 1978-05-18 1980-04-15 Lord Corporation Damage-preventive coatings
US4284089A (en) 1978-10-02 1981-08-18 Ray Jon P Simulated smoking device
FR2438821B1 (en) 1978-10-13 1981-03-27 France Etat
US4276243A (en) 1978-12-08 1981-06-30 Western Electric Company, Inc. Vapor delivery control system and method
US4280629A (en) 1979-01-08 1981-07-28 Anchor Brush Company, Inc. Container for nail polish or the like
US4372210A (en) * 1979-01-10 1983-02-08 Gte Products Corporation Pyrotechnic cap with mechanically desensitized composition
US4205673A (en) 1979-02-05 1980-06-03 Mine Safety Appliances Company Breathing apparatus with an automatic firing mechanism
US4219031A (en) 1979-03-05 1980-08-26 Philip Morris Incorporated Smoking product having core of fibrillar carbonized matter
US4229931A (en) 1979-03-05 1980-10-28 Deere & Company Hydraulic height sensing system with cylinder by-pass
US4423071A (en) 1979-03-06 1983-12-27 Sanofi Polyol derivatives, processes for preparing the same and their uses in therapeutics
US4654370A (en) 1979-03-12 1987-03-31 Abbott Laboratories Glyceryl valproates
US4280409A (en) * 1979-04-09 1981-07-28 The United States Of America As Represented By The Secretary Of The Navy Molten metal-liquid explosive device
US4205758A (en) 1979-04-10 1980-06-03 Johnson Harley D Replacement oil pan plug
GB2049651B (en) * 1979-04-30 1982-12-01 Brock Fireworks Coating surfaces with explosive or pyrotechniccompositions
US4251525A (en) 1979-05-25 1981-02-17 Smithkline Corporation 3-Allyl-7,8-dihydroxy-6-halo-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine derivatives
US4229447A (en) 1979-06-04 1980-10-21 American Home Products Corporation Intraoral methods of using benzodiazepines
US4329924A (en) 1979-09-11 1982-05-18 Etat Francais Represente Par Le Delegue General Pour L'armement Electric primer with conductive composition
GB2064296B (en) 1979-11-16 1983-06-22 Imp Group Ltd Cigarette or cigarette-like device which produces aerosol in smoke
EP0039369B1 (en) 1980-05-02 1983-06-15 Schering Corporation Beclomethasone ester solvates, process for their preparation, and preparation of a formulation
US4391285A (en) 1980-05-09 1983-07-05 Philip Morris, Incorporated Smoking article
US4347855A (en) 1980-07-23 1982-09-07 Philip Morris Incorporated Method of making smoking articles
CA1145142A (en) 1980-10-10 1983-04-26 Alan L. Davitt Delay composition for detonators
US4303083A (en) 1980-10-10 1981-12-01 Burruss Jr Robert P Device for evaporation and inhalation of volatile compounds and medications
JPS6056551B2 (en) * 1980-10-31 1985-12-10 Dainippon Printing Co Ltd
JPS5778968U (en) 1980-10-31 1982-05-15
US4376767A (en) 1981-01-02 1983-03-15 Merck & Co., Inc. Pyridylmethyl esters of selected bio-affecting carboxylic acids
US4346059A (en) 1981-03-03 1982-08-24 Donald Spector Aroma-generating lamp structure
DE3116951C2 (en) 1981-04-29 1984-12-20 Draegerwerk Ag, 2400 Luebeck, De
US4419153A (en) 1981-05-21 1983-12-06 Aktiebolaget Bofors Pyrotechnical delay charge
FR2506927B1 (en) 1981-05-29 1986-09-26 France Etat Electro-pyrotechnic initiator hot exploding wire or a coaxial structure
JPS5876038A (en) 1981-10-28 1983-05-09 Masayuki Takamori Evaporation apparatus of insecticide or aromatic agent
JPS58225001A (en) 1982-06-22 1983-12-27 Masayuki Takamori Tape for vaporizing insecticide or aromatic under heating
DE3224849A1 (en) 1982-07-02 1984-01-05 Christensen Plantorgan Werk Dampfinhaliergeraet
GB2123948B (en) * 1982-07-21 1986-01-15 Neptune Systems Limited Heating element
US4556539A (en) 1982-08-27 1985-12-03 Donald Spector Disc-playing aroma generator
US4508726A (en) 1982-09-16 1985-04-02 The Upjohn Company Treatment of panic disorders with alprazolam
US4693868A (en) 1982-09-30 1987-09-15 Dainihon Jochugiku Co., Ltd. Thermal fumigator for drugs
US4474191A (en) 1982-09-30 1984-10-02 Steiner Pierre G Tar-free smoking devices
JPS6320298Y2 (en) 1983-01-06 1988-06-06
US4526758A (en) 1983-01-17 1985-07-02 Alengoz Anton S Starting device for self-contained breathing apparatus
US4484960A (en) 1983-02-25 1984-11-27 E. I. Du Pont De Nemours And Company High-temperature-stable ignition powder
US4753758A (en) 1983-05-19 1988-06-28 Intertech Resources Inc. Respiratory humidifier
US4523589A (en) 1983-06-29 1985-06-18 Krauser Robert S Method and apparatus for treating ailments
DE3326089A1 (en) 1983-07-20 1985-02-07 Goedecke Ag For inhalation dosage form in particular of calcium antagonists
EP0133795B1 (en) 1983-08-01 1989-01-18 THE McLEAN HOSPITAL CORPORATION Gaba esters and gaba analogue esters
US4588721A (en) 1983-09-12 1986-05-13 The Upjohn Company Treatment of negative symptoms of schizophrenia
DE3478900D1 (en) 1983-11-08 1989-08-17 Bunnell Life Systems Inc Humidifier, particularly for pulmonary assistance systems
GB8405190D0 (en) 1984-02-28 1984-04-04 British Petroleum Co Plc Thermoplastic elastomer composition
US4627963A (en) 1984-02-29 1986-12-09 Lad Technology, Inc. Heat activated dispenser and method of dispensing a vapor therefrom
US4683231A (en) 1984-03-02 1987-07-28 Research Foundation For Mental Hygiene, Inc. Method of preventing withdrawal symptoms associated with the cessation or reduction of tobacco smoking
US4963367A (en) 1984-04-27 1990-10-16 Medaphore, Inc. Drug delivery compositions and methods
US4647428A (en) 1984-06-04 1987-03-03 Gyulay Joseph M Air freshener method
US4755508A (en) 1984-06-26 1988-07-05 Merck & Co., Inc. Benzodiazepine analogs and use as antogonists of gastrin and cholecystokinin
US4671270A (en) 1984-07-06 1987-06-09 Midori Anzen Industry Co., Ltd. Portable oxygen inhaler
US4854331A (en) 1984-09-14 1989-08-08 R. J. Reynolds Tobacco Company Smoking article
US4793365A (en) 1984-09-14 1988-12-27 R. J. Reynolds Tobacco Company Smoking article
US5067499A (en) 1984-09-14 1991-11-26 R. J. Reynolds Tobacco Company Smoking article
US5042509A (en) 1984-09-14 1991-08-27 R. J. Reynolds Tobacco Company Method for making aerosol generating cartridge
US4647433A (en) 1984-10-01 1987-03-03 Donald Spector Long-life aroma-generating capsule
CN1024996C (en) 1984-12-21 1994-06-15 美国J·R瑞诺兹烟草公司 Smoking article
GB8501015D0 (en) 1985-01-16 1985-02-20 Riker Laboratories Inc Drug
US5119834A (en) 1985-04-15 1992-06-09 R. J. Reynolds Tobacco Company Smoking article with improved substrate
US4928714A (en) 1985-04-15 1990-05-29 R. J. Reynolds Tobacco Company Smoking article with embedded substrate
EP0223831B1 (en) 1985-05-22 1992-07-15 Liposome Technology, Inc. Liposome inhalation method and system
US4800903A (en) 1985-05-24 1989-01-31 Ray Jon P Nicotine dispenser with polymeric reservoir of nicotine
US4722334A (en) 1985-07-16 1988-02-02 Transpirator Technologies, Inc. Method and apparatus for pulmonary and cardiovascular conditioning of racehorses and competition animals
US4989619A (en) 1985-08-26 1991-02-05 R. J. Reynolds Tobacco Company Smoking article with improved fuel element
US5020548A (en) 1985-08-26 1991-06-04 R. J. Reynolds Tobacco Company Smoking article with improved fuel element
US5060666A (en) 1985-10-28 1991-10-29 R. J. Reynolds Tobacco Company Smoking article with tobacco jacket
US5033483A (en) 1985-10-28 1991-07-23 R. J. Reynolds Tobacco Company Smoking article with tobacco jacket
US4756318A (en) 1985-10-28 1988-07-12 R. J. Reynolds Tobacco Company Smoking article with tobacco jacket
US4793366A (en) 1985-11-12 1988-12-27 Hill Ira D Nicotine dispensing device and methods of making the same
DE3542447C2 (en) * 1985-11-30 1993-11-18 Diehl Gmbh & Co Laser-sensitive igniter
US4757764A (en) 1985-12-20 1988-07-19 The Ensign-Bickford Company Nonelectric blasting initiation signal control system, method and transmission device therefor
US4773389A (en) 1986-02-19 1988-09-27 Chori Company, Ltd. Self-heating foodstuff container
JPS62204756A (en) 1986-03-04 1987-09-09 Daiken Iko Kk Drug volatilizing method and apparatus
DE3767615D1 (en) 1986-03-10 1991-02-28 Kurt Burghart Pharmaceutical and process for its production.
US4708151A (en) 1986-03-14 1987-11-24 R. J. Reynolds Tobacco Company Pipe with replaceable cartridge
US4700629A (en) 1986-05-02 1987-10-20 The United States Of America As Represented By The United States Department Of Energy Optically-energized, emp-resistant, fast-acting, explosion initiating device
JPS62261859A (en) * 1986-05-08 1987-11-14 Asahi Chem Ind Co Ltd Composition for heating food and drink
EP0244837A1 (en) * 1986-05-08 1987-11-11 Asahi Kasei Kogyo Kabushiki Kaisha Self-heating container
US4765347A (en) 1986-05-09 1988-08-23 R. J. Reynolds Tobacco Company Aerosol flavor delivery system
US4771795A (en) 1986-05-15 1988-09-20 R. J. Reynolds Tobacco Company Smoking article with dual burn rate fuel element
US4917120A (en) 1986-05-21 1990-04-17 Advanced Tobacco Products, Inc. Nicotine impact modification
US4774971A (en) 1986-06-03 1988-10-04 Vieten Michael J Cigarette substitute
US4801411A (en) 1986-06-05 1989-01-31 Southwest Research Institute Method and apparatus for producing monosize ceramic particles
US4735217A (en) 1986-08-21 1988-04-05 The Procter & Gamble Company Dosing device to provide vaporized medicament to the lungs as a fine aerosol
GB8622606D0 (en) 1986-09-19 1986-10-22 Imp Tobacco Ltd Smoking article
US4858630A (en) 1986-12-08 1989-08-22 R. J. Reynolds Tobacco Company Smoking article with improved aerosol forming substrate
EP0270944A3 (en) 1986-12-12 1989-03-15 R.J. Reynolds Tobacco Company Impact modifying agent for use with smoking articles
US4721224A (en) * 1986-12-31 1988-01-26 Nittoseiki Kabushiki Kaisha Pressure vessel having pressure releasing mechanism
US4734560A (en) 1987-01-20 1988-03-29 Medical Enterprises, Ltd. Vaporizing unit
US4819665A (en) 1987-01-23 1989-04-11 R. J. Reynolds Tobacco Company Aerosol delivery article
DE3883266D1 (en) 1987-02-16 1993-09-23 Nitro Nobel Ab Detonator.
US4924883A (en) 1987-03-06 1990-05-15 R. J. Reynolds Tobacco Company Smoking article
WO1988008304A1 (en) 1987-04-23 1988-11-03 Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. Pharmaceutical composition
US4889850A (en) 1987-05-11 1989-12-26 Thornfeldt Carl R Treatment of colic and teething
US5017575A (en) 1987-06-09 1991-05-21 Golwyn Daniel H Treatment of immunologically based disorders, specifically Crohn's disease
GB8713645D0 (en) 1987-06-11 1987-07-15 Imp Tobacco Ltd Smoking device
US5019122A (en) 1987-08-21 1991-05-28 R. J. Reynolds Tobacco Company Smoking article with an enclosed heat conductive capsule containing an aerosol forming substance
ES2034394T3 (en) 1987-09-29 1993-04-01 Swedish Ordnance - Ffv/Bofors Ab Process for the preparation of a pyrotechnic charge.
US5072726A (en) 1987-10-09 1991-12-17 University Of Pittsburgh Of The Commonwealth System Of Higher Education Vaporizer for inhalation anesthetics during high-frequency jet ventilation and associated method
US4911157A (en) 1988-01-07 1990-03-27 Pegasus Research Corporation Self-regulating, heated nebulizer system
US4906417A (en) 1988-02-08 1990-03-06 Associated Mills Inc. Humidifier
JPH01221313A (en) 1988-02-29 1989-09-04 Hayashi Teruaki Sublimation-releasable medicine composition and releasing system thereof
DE68913123T2 (en) * 1988-03-18 1994-08-25 Nissin Food Products Ltd Heat generating element.
US4853517A (en) 1988-03-28 1989-08-01 John G. Bowen Vaporizing unit
DE3815221C2 (en) 1988-05-04 1995-06-29 Gradinger F Hermes Pharma Use of a retinol and / or retinoic acid esters containing pharmaceutical preparation for inhalation for acting on the mucous membranes of the tracheo-bronchial tract, including the lung alveoli
US5137034A (en) 1988-05-16 1992-08-11 R. J. Reynolds Tobacco Company Smoking article with improved means for delivering flavorants
US4881556A (en) 1988-06-06 1989-11-21 R. J. Reynolds Tobacco Company Low CO smoking article
US5264433A (en) 1988-07-07 1993-11-23 Fujisawa Pharmaceutical Co., Ltd. Benzodiazepine derivatives
US4955945A (en) 1988-07-13 1990-09-11 Weick Heinz Hermann Dispenser for the vaporization of active substances to be inhaled
US5345951A (en) 1988-07-22 1994-09-13 Philip Morris Incorporated Smoking article
US4852561A (en) 1988-07-27 1989-08-01 Sperry C R Inhalation device
US4947875A (en) 1988-09-08 1990-08-14 R. J. Reynolds Tobacco Company Flavor delivery articles utilizing electrical energy
US4947874A (en) 1988-09-08 1990-08-14 R. J. Reynolds Tobacco Company Smoking articles utilizing electrical energy
EP0358114A3 (en) 1988-09-08 1990-11-14 R.J. Reynolds Tobacco Company Aerosol delivery articles utilizing electrical energy
US4922901A (en) 1988-09-08 1990-05-08 R. J. Reynolds Tobacco Company Drug delivery articles utilizing electrical energy
USRE36744E (en) 1988-09-16 2000-06-20 Ribogene, Inc. Nasal administration of benzodiazepine hypnotics
US4963289A (en) 1988-09-19 1990-10-16 The United States Of America As Represented By The United States Department Of Energy Method for producing monodisperse aerosols
US4917830A (en) 1988-09-19 1990-04-17 The United States Of America As Represented By The United States Department Of Energy Monodisperse aerosol generator
US5511726A (en) 1988-09-23 1996-04-30 Battelle Memorial Institute Nebulizer device
US4984158A (en) 1988-10-14 1991-01-08 Hillsman Dean Metered dose inhaler biofeedback training and evaluation system
US4917119A (en) * 1988-11-30 1990-04-17 R. J. Reynolds Tobacco Company Drug delivery article
US5049389A (en) 1988-12-14 1991-09-17 Liposome Technology, Inc. Novel liposome composition for the treatment of interstitial lung diseases
US4881541A (en) 1988-12-21 1989-11-21 The Regents Of The University Of California Vaporizer for an anesthetic having a vapor pressure about one atmosphere
US4892037A (en) 1989-01-03 1990-01-09 The United States Of America As Represented By The Secretary Of The Army Self consumable initiator
GB8900267D0 (en) 1989-01-06 1989-03-08 Riker Laboratories Inc Narcotic analgesic formulations and apparatus containing same
US4892109A (en) 1989-03-08 1990-01-09 Brown & Williamson Tobacco Corporation Simulated smoking article
DE3908161C2 (en) 1989-03-13 1992-09-03 B.A.T. Cigarettenfabriken Gmbh, 2000 Hamburg, De
GB8909891D0 (en) 1989-04-28 1989-06-14 Riker Laboratories Inc Device
WO1990013327A1 (en) 1989-04-28 1990-11-15 Riker Laboratories, Inc. Dry powder inhalation device
DE69027992D1 (en) 1989-05-05 1996-09-05 North Sydney Area Health Serv Increasing fertility
US5027707A (en) 1989-05-08 1991-07-02 Olin Corporation Electric primer with reduced RF and ESD hazard
US4941483A (en) 1989-09-18 1990-07-17 R. J. Reynolds Tobacco Company Aerosol delivery article
US6313176B1 (en) 1989-10-17 2001-11-06 Everett J. Ellinwood, Jr. Dosing method of administering deprenyl via intraoral administration or inhalation administration
US6048857A (en) 1989-10-17 2000-04-11 Ellinwood, Jr.; Everett H. Dosing method of administering medicaments via inhalation administration
US5707644A (en) 1989-11-04 1998-01-13 Danbiosyst Uk Limited Small particle compositions for intranasal drug delivery
US5224498A (en) 1989-12-01 1993-07-06 Philip Morris Incorporated Electrically-powered heating element
US5060671A (en) 1989-12-01 1991-10-29 Philip Morris Incorporated Flavor generating article
US5144962A (en) 1989-12-01 1992-09-08 Philip Morris Incorporated Flavor-delivery article
EP0504263B1 (en) 1989-12-05 1997-08-13 Ramsey Foundation Neurologic agents for nasal administration to the brain
US5109180A (en) 1989-12-14 1992-04-28 Phillips Petroleum Company Apparatus providing a shatter-resistant electric lamp
US5580575A (en) 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
US5733572A (en) 1989-12-22 1998-03-31 Imarx Pharmaceutical Corp. Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles
GB9000421D0 (en) 1990-01-09 1990-03-07 Boc Group Plc Improvements in anaesthetic vaporisers
US5376386A (en) 1990-01-24 1994-12-27 British Technology Group Limited Aerosol carriers
US5156170A (en) 1990-02-27 1992-10-20 R. J. Reynolds Tobacco Company Cigarette
US5099861A (en) 1990-02-27 1992-03-31 R. J. Reynolds Tobacco Company Aerosol delivery article
US5118494A (en) 1990-03-23 1992-06-02 Minnesota Mining And Manufacturing Company Use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations
US5366770A (en) 1990-04-17 1994-11-22 Xingwu Wang Aerosol-plasma deposition of films for electronic cells
US5229382A (en) 1990-04-25 1993-07-20 Lilly Industries Limited 2-methyl-thieno-benzodiazepine
US5627178A (en) 1991-04-23 1997-05-06 Lilly Industries Limited 2-methyl-thieno-benzodiazepine
US5817656A (en) 1991-04-23 1998-10-06 Eli Lilly And Company Mental disorders
US5605897A (en) 1991-04-23 1997-02-25 Eli Lilly And Company 2-methyl-thieno-benzodiazepine
US5192548A (en) 1990-04-30 1993-03-09 Riker Laboratoires, Inc. Device
RU2160736C2 (en) 1990-06-07 2000-12-20 Зенека Лимитед Indole derivatives and physiologically acceptable salts and solvates thereof, methods of preparing thereof, drug for treatment or prophylaxes of clinical states for which administration of 5-ht1-like receptor agonist, and method of preparing thereof
US5167242A (en) 1990-06-08 1992-12-01 Kabi Pharmacia Aktiebolaq Nicotine-impermeable container and method of fabricating the same
US5126123A (en) 1990-06-28 1992-06-30 Glaxo, Inc. Aerosol drug formulations
DE69110785D1 (en) 1990-08-02 1995-08-03 Boc Group Plc Anesthetic vaporizers.
US5060667A (en) 1990-08-16 1991-10-29 Brown & Williamson Tobacco Corporation Smoking article
US5292499A (en) 1990-09-11 1994-03-08 University Of Wales College Of Cardiff Method of preparing medical aerosol formulations including drug dissolved in reverse micelles
US5166202A (en) 1990-09-19 1992-11-24 Trustees Of The University Of Pennsylvania Method for the treatment of panic disorder
US5175152A (en) 1990-09-28 1992-12-29 Singh Nikhilesh N Composition containing ephedrine base and alkyl salicylate for the delivery of ephedrine base in vapor form
US5255674A (en) 1990-09-28 1993-10-26 Forsvarets Forskningsinstitutt Portable heating and humidifying device
US5519019A (en) 1990-12-21 1996-05-21 Gyogyszerkutato Intezet N-acyl-2,3-benzoidazepine derivatives, pharmaceutical compositions containing them and process for preparing same
CA2057504C (en) 1990-12-21 2002-02-12 Ferenc Andrasi Process for preparing new n-acyl-2,3-benzodiazepine derivatives, their acid addition salts and pharmaceutical compositions containing the same
FR2671487B1 (en) 1991-01-14 1993-03-19 Oreal Use of a growth factor in a slimming composition.
DE69229070T2 (en) 1991-02-09 1999-11-18 B S D Bio Science Dev Snc Di O Anti-reactive anti-asthmatic effect of aspirin by inhalation
DE69430303T2 (en) 1991-03-05 2002-11-28 Aradigm Corp A method and apparatus for correcting a zero signal of a pressure sensor for a flow meter
US5394866A (en) 1991-03-05 1995-03-07 Aradigm Corporation Automatic aerosol medication delivery system and methods
US5404871A (en) 1991-03-05 1995-04-11 Aradigm Delivery of aerosol medications for inspiration
US5591368A (en) * 1991-03-11 1997-01-07 Philip Morris Incorporated Heater for use in an electrical smoking system
US5249586A (en) 1991-03-11 1993-10-05 Philip Morris Incorporated Electrical smoking
US5186164A (en) 1991-03-15 1993-02-16 Puthalath Raghuprasad Mist inhaler
US5993805A (en) 1991-04-10 1999-11-30 Quadrant Healthcare (Uk) Limited Spray-dried microparticles and their use as therapeutic vehicles
US5938117A (en) 1991-04-24 1999-08-17 Aerogen, Inc. Methods and apparatus for dispensing liquids as an atomized spray
US5164740A (en) 1991-04-24 1992-11-17 Yehuda Ivri High frequency printing mechanism
GB9109021D0 (en) 1991-04-26 1991-06-12 Boc Group Plc Dosing pump
US5261424A (en) 1991-05-31 1993-11-16 Philip Morris Incorporated Control device for flavor-generating article
US5160664A (en) 1991-05-31 1992-11-03 Msp Corporation High output monodisperse aerosol generator
US5177071A (en) 1991-06-17 1993-01-05 Merck & Co., Inc. 1,4-benzodiazepines with 6-membered heterocyclic rings to treat panic and anxiety disorder
US5285798A (en) 1991-06-28 1994-02-15 R. J. Reynolds Tobacco Company Tobacco smoking article with electrochemical heat source
CA2069687A1 (en) * 1991-06-28 1992-12-29 Chandra Kumar Banerjee Tobacco smoking article with electrochemical heat source
JPH0539442A (en) * 1991-08-02 1993-02-19 Genji Naemura Electrically conductive heat generating fluid
EP0532194A1 (en) 1991-09-10 1993-03-17 Philip Morris Products Inc. Thermally-regulated flavor generator
US5457100A (en) 1991-12-02 1995-10-10 Daniel; David G. Method for treatment of recurrent paroxysmal neuropsychiatric
US5246417A (en) 1991-12-11 1993-09-21 Alza Corporation Indicator for iontophoresis system
US5363842A (en) 1991-12-20 1994-11-15 Circadian, Inc. Intelligent inhaler providing feedback to both patient and medical professional
GB9200047D0 (en) 1992-01-03 1992-02-26 Univ Alberta Nicotine-containing nasal spray
US5229120A (en) 1992-02-05 1993-07-20 Devincent James F Treatment for cocaine abuse
US5639441A (en) 1992-03-06 1997-06-17 Board Of Regents Of University Of Colorado Methods for fine particle formation
US5509354A (en) * 1992-03-26 1996-04-23 Centuri Corporation Igniter holder
US5318033A (en) 1992-04-17 1994-06-07 Hewlett-Packard Company Method and apparatus for increasing the frame rate and resolution of a phased array imaging system
US5584701A (en) 1992-05-13 1996-12-17 University Of Florida Research Foundation, Incorporated Self regulating lung for simulated medical procedures
US5391081A (en) 1992-05-13 1995-02-21 University Of Florida Research Foundation, Incorporated Method and apparatus for simulating neuromuscular stimulation during medical surgery
DK64592D0 (en) 1992-05-14 1992-05-14 Carlbiotech Ltd As Peptides for therapeutic treatment
US5525329A (en) 1992-05-21 1996-06-11 The Johns Hopkins University Inhibition of phosphodiesterase in olfactory mucosa
CA2115444C (en) 1992-06-12 2000-10-03 Yuji Makino Preparation for intratracheobronchial administration
US5607691A (en) 1992-06-12 1997-03-04 Affymax Technologies N.V. Compositions and methods for enhanced drug delivery
US5622944A (en) 1992-06-12 1997-04-22 Affymax Technologies N.V. Testosterone prodrugs for improved drug delivery
US6258341B1 (en) 1995-04-14 2001-07-10 Inhale Therapeutic Systems, Inc. Stable glassy state powder formulations
US5284133A (en) 1992-07-23 1994-02-08 Armstrong Pharmaceuticals, Inc. Inhalation device with a dose-timer, an actuator mechanism, and patient compliance monitoring means
US5322075A (en) 1992-09-10 1994-06-21 Philip Morris Incorporated Heater for an electric flavor-generating article
US5333106A (en) 1992-10-09 1994-07-26 Circadian, Inc. Apparatus and visual display method for training in the power use of aerosol pharmaceutical inhalers
WO1994009842A1 (en) 1992-10-28 1994-05-11 Rosen Charles A Method and devices for delivering drugs by inhalation
DE69317514D1 (en) 1992-11-27 1998-04-23 Nitro Nobel Ab Delay charge and element, and detonator with such a charge
US5558085A (en) 1993-01-29 1996-09-24 Aradigm Corporation Intrapulmonary delivery of peptide drugs
US5507277A (en) * 1993-01-29 1996-04-16 Aradigm Corporation Lockout device for controlled release of drug from patient-activateddispenser
US5743250A (en) 1993-01-29 1998-04-28 Aradigm Corporation Insulin delivery enhanced by coached breathing
US5724957A (en) 1993-01-29 1998-03-10 Aradigm Corporation Intrapulmonary delivery of narcotics
US5970973A (en) 1993-01-29 1999-10-26 Aradigm Corporation Method of delivering insulin lispro
US6024090A (en) 1993-01-29 2000-02-15 Aradigm Corporation Method of treating a diabetic patient by aerosolized administration of insulin lispro
US5934272A (en) 1993-01-29 1999-08-10 Aradigm Corporation Device and method of creating aerosolized mist of respiratory drug
US5694919A (en) 1993-01-29 1997-12-09 Aradigm Corporation Lockout device for controlled release of drug from patient-activated dispenser
US5364838A (en) 1993-01-29 1994-11-15 Miris Medical Corporation Method of administration of insulin
US5888477A (en) 1993-01-29 1999-03-30 Aradigm Corporation Use of monomeric insulin as a means for improving the bioavailability of inhaled insulin
US5915378A (en) 1993-01-29 1999-06-29 Aradigm Corporation Creating an aerosolized formulation of insulin
US5372148A (en) 1993-02-24 1994-12-13 Philip Morris Incorporated Method and apparatus for controlling the supply of energy to a heating load in a smoking article
US5468936A (en) 1993-03-23 1995-11-21 Philip Morris Incorporated Heater having a multiple-layer ceramic substrate and method of fabrication
GB9310412D0 (en) 1993-05-20 1993-07-07 Danbiosyst Uk Nasal nicotine system
US5497763A (en) 1993-05-21 1996-03-12 Aradigm Corporation Disposable package for intrapulmonary delivery of aerosolized formulations
US5666977A (en) 1993-06-10 1997-09-16 Philip Morris Incorporated Electrical smoking article using liquid tobacco flavor medium delivery system
US5894841A (en) 1993-06-29 1999-04-20 Ponwell Enterprises Limited Dispenser
DE4321926C1 (en) 1993-07-01 1994-06-16 Draegerwerk Ag Device for operating oxygen-emitting cartridge in breathing protection appts. - involves striker spring fixed in retainer, at end of which is striker hammer operating ignition mechanism
DE9310438U1 (en) 1993-07-13 1993-09-16 Festo Kg valve station
US5388574A (en) 1993-07-29 1995-02-14 Ingebrethsen; Bradley J. Aerosol delivery article
DE4328243C1 (en) 1993-08-19 1995-03-09 Sven Mielordt Smoke or inhaler
US5456247A (en) 1993-08-26 1995-10-10 Iowa State University Research Foundation, Inc. Method for delivering drugs soluble in a vaporization vehicle
US5462740A (en) 1993-09-17 1995-10-31 Athena Neurosciences, Inc. Rectally-administered, epileptic-seizure-inhibiting composition
DE69427832T2 (en) 1993-11-01 2001-11-22 Pharmacia Ab Drug delivery preparation containing nicotine or a derivative thereof and starch microspheres, and process for its manufacture
FI98270C (en) 1993-11-29 1997-05-26 Instrumentarium Oy Method and arrangement in connection with vaporizing an anesthetic
DE69530571D1 (en) 1994-01-07 2003-06-05 Smithkline Beecham Corp bicyclic fibrinogen
US5543434A (en) 1994-02-25 1996-08-06 Weg; Stuart L. Nasal administration of ketamine to manage pain
US5626360A (en) 1994-03-14 1997-05-06 Morton International, Inc. Linear igniters for airbag inflators
US5451408A (en) 1994-03-23 1995-09-19 Liposome Pain Management, Ltd. Pain management with liposome-encapsulated analgesic drugs
CN1082365C (en) 1994-03-30 2002-04-10 普罗克特和甘保尔公司 Combined skin moisturizing and cleaning bar compsn.
US6102036A (en) 1994-04-12 2000-08-15 Smoke-Stop Breath activated inhaler
DE69523301T2 (en) 1994-05-13 2002-07-04 Aradigm Corp A narcotic aerosol formulation containing
US5457101A (en) 1994-06-03 1995-10-10 Eli Lilly And Company Thieno[1,5]benzoidiazepine use
US5573565A (en) * 1994-06-17 1996-11-12 The United States Of America As Represented By The Department Of Energy Method of making an integral window hermetic fiber optic component
WO1996000071A1 (en) 1994-06-23 1996-01-04 The Procter & Gamble Company Treatment of nicotine craving and/or smoking withdrawal symptoms with a liquid nasal composition containing nicotine and caffeine or xanthine
WO1996000070A1 (en) 1994-06-23 1996-01-04 The Procter & Gamble Company Treatment of nicotine craving and/or smoking withdrawal symptoms with an oral composition containing nicotine and caffeine or xanthine
WO1996000069A1 (en) 1994-06-23 1996-01-04 The Procter & Gamble Company Treatment of nicotine craving and/or smoking withdrawal symptoms with a solid or semi-solid composition containing nicotine and caffeine or xanthine, especially for nasal administration
CA2152684A1 (en) 1994-07-01 1996-01-02 Richard Anthony Henry Aerosol delivery of midazolam
DE4425255A1 (en) 1994-07-16 1996-01-18 Asta Medica Ag Formulation for inhalation
US5456677A (en) 1994-08-22 1995-10-10 Spector; John E. Method for oral spray administration of caffeine
EP0777657A4 (en) 1994-08-22 1997-07-16
US5522385A (en) 1994-09-27 1996-06-04 Aradigm Corporation Dynamic particle size control for aerosolized drug delivery
WO1996010663A1 (en) 1994-09-30 1996-04-11 M & J Fibretech A/S A plant and a process for dry-producing a web-formed product
US5672843A (en) 1994-10-05 1997-09-30 Ici Americas Inc. Single charge pyrotechnic
US5454363A (en) * 1994-10-14 1995-10-03 Japan As Represented By Director General Of Agency Of Industrial Science And Technology High-temperature exothermic device
WO1996011689A1 (en) 1994-10-14 1996-04-25 Glaxo Wellcome Spa Use of cck-b receptor antagonists for the treatment of sleep disorders
US6013050A (en) 1995-10-20 2000-01-11 Powderject Research Limited Particle delivery
US5767117A (en) 1994-11-18 1998-06-16 The General Hospital Corporation Method for treating vascular headaches
US5697896A (en) 1994-12-08 1997-12-16 Alza Corporation Electrotransport delivery device
US5747001A (en) 1995-02-24 1998-05-05 Nanosystems, L.L.C. Aerosols containing beclomethazone nanoparticle dispersions
EP0810853B1 (en) 1995-02-24 2004-08-25 Elan Pharma International Limited Aerosols containing nanoparticle dispersions
DE19507410C2 (en) 1995-03-03 1997-05-22 Gsf Forschungszentrum Umwelt Method and apparatus for the production of aerosols
US5641938A (en) 1995-03-03 1997-06-24 Primex Technologies, Inc. Thermally stable gas generating composition
US5612053A (en) 1995-04-07 1997-03-18 Edward Mendell Co., Inc. Controlled release insufflation carrier for medicaments
DE69622166D1 (en) 1995-04-14 2002-08-08 Smithkline Beecham Corp Metered dose inhaler for albuterol
US5690809A (en) 1995-04-18 1997-11-25 Center For Research, Inc. In situ mitigation of coke buildup in porous catalysts by pretreatment of hydrocarbon feed to reduce peroxides and oxygen impurities
US5725756A (en) 1995-04-18 1998-03-10 Center For Research, Inc. In situ mitigation of coke buildup in porous catalysts with supercritical reaction media
US5776928A (en) 1995-04-21 1998-07-07 Eli Lilly And Company Method for treating dyskinesias with olanzapine
US5809997A (en) 1995-05-18 1998-09-22 Medtrac Technologies, Inc. Electronic medication chronolog device
US5623115A (en) 1995-05-30 1997-04-22 Morton International, Inc. Inflator for a vehicle airbag system and a pyrogen igniter used therein
US5874481A (en) 1995-06-07 1999-02-23 Alliance Pharmaceutical Corp. Fluorochemical solutions for the delivery of lipophilic pharmaceutical agents
CA2152452C (en) 1995-06-22 1998-02-03 Robert Freiman Self heating container
US6955819B2 (en) 1998-09-29 2005-10-18 Zars, Inc. Methods and apparatus for using controlled heat to regulate transdermal and controlled release delivery of fentanyl, other analgesics, and other medical substances
US6245347B1 (en) 1995-07-28 2001-06-12 Zars, Inc. Methods and apparatus for improved administration of pharmaceutically active compounds
US5660413A (en) 1995-08-24 1997-08-26 Trw Vehicle Safety Systems Inc. Air bag inflator with laser diode initiator
US5758637A (en) 1995-08-31 1998-06-02 Aerogen, Inc. Liquid dispensing apparatus and methods
US5586550A (en) 1995-08-31 1996-12-24 Fluid Propulsion Technologies, Inc. Apparatus and methods for the delivery of therapeutic liquids to the respiratory system
EP0761249B1 (en) 1995-09-12 2003-10-01 Siemens-Elema AB Anaesthetic apparatus
US5649554A (en) 1995-10-16 1997-07-22 Philip Morris Incorporated Electrical lighter with a rotatable tobacco supply
US6017963A (en) 1995-11-14 2000-01-25 Euro-Celtique, S.A. Formulation for intranasal administration
US5564442A (en) 1995-11-22 1996-10-15 Angus Collingwood MacDonald Battery powered nicotine vaporizer
US6041777A (en) 1995-12-01 2000-03-28 Alliance Pharmaceutical Corp. Methods and apparatus for closed-circuit ventilation therapy
DE19546341C2 (en) * 1995-12-12 1999-03-18 Schneider Alexander By laser radiation of low intensity initiierbarer, optical detonators
US6133327A (en) 1995-12-14 2000-10-17 Taisho Pharmaceutical Co., Ltd. Aerosol preparation
DE19648269B4 (en) 1995-12-21 2005-02-24 Maquet Critical Care Ab A method for gasifying a liquid anesthetic and a carburetor
US5686691A (en) 1995-12-22 1997-11-11 Oea, Inc. Slurry-loadable electrical initiator
US5829436A (en) 1996-02-05 1998-11-03 Aradigm Corporation Ventilation imaging using a fine particle aerosol generator
EP0955885A4 (en) 1996-02-05 1999-12-22
CA2244089C (en) 1996-02-19 2009-06-02 Monash University Dermal penetration enhancers and drug delivery systems involving same
GB9604329D0 (en) 1996-02-29 1996-05-01 Ici Plc Electrostatic spraying
EP0828489A4 (en) 1996-03-13 2001-04-04 Univ Yale Smoking cessation treatments using naltrexone and related compounds
CA2250186A1 (en) 1996-03-25 1997-10-02 Eli Lilly And Company Method for treating migraine pain
WO1997035584A1 (en) 1996-03-25 1997-10-02 Eli Lilly And Company Method for treating pain
US5944012A (en) 1996-03-25 1999-08-31 Pera; Ivo E. Method for dispensing antioxidant vitamins by inhalation background of the invention
US5875776A (en) 1996-04-09 1999-03-02 Vivorx Pharmaceuticals, Inc. Dry powder inhaler
DE19616627A1 (en) * 1996-04-26 1997-11-06 Dynamit Nobel Ag igniter
GB2312848B (en) 1996-04-26 1999-11-17 Bespak Plc Controlled flow inhalers
CA2252814A1 (en) 1996-04-29 1997-11-06 Dura Pharmaceuticals, Inc. Methods of dry powder inhalation
US5959242A (en) 1996-05-14 1999-09-28 Talley Defense Systems, Inc. Autoignition composition
US5743251A (en) 1996-05-15 1998-04-28 Philip Morris Incorporated Aerosol and a method and apparatus for generating an aerosol
US5985309A (en) 1996-05-24 1999-11-16 Massachusetts Institute Of Technology Preparation of particles for inhalation
US5874064A (en) 1996-05-24 1999-02-23 Massachusetts Institute Of Technology Aerodynamically light particles for pulmonary drug delivery
US5929093A (en) 1996-06-13 1999-07-27 Mayo Foundation For Medical Education And Research Bifunctional acetylcholinesterase reactivators
DE69719719D1 (en) 1996-06-17 2003-04-17 Japan Tobacco Inc Aroma-producing articles and flavor generation device
US6089857A (en) 1996-06-21 2000-07-18 Japan Tobacco, Inc. Heater for generating flavor and flavor generation appliance
GB9613015D0 (en) 1996-06-21 1996-08-28 Reckitt & Colman Inc Device
EP0816674A1 (en) 1996-06-24 1998-01-07 Simmonds Precision Engine Systems, Inc. Ignition methods and apparatus using broadband laser energy
CA2259418A1 (en) 1996-07-11 1998-01-22 Farmarc Nederland B.V. Pharmaceutical composition containing acid addition salt of basic drug
US5763813A (en) 1996-08-26 1998-06-09 Kibbutz Kfar Etzion Composite armor panel
DK0951280T3 (en) 1996-10-03 2004-05-17 Hermes Biosciences Inc Hydrophilic microparticles and methods for their preparation
US5833891A (en) 1996-10-09 1998-11-10 The University Of Kansas Methods for a particle precipitation and coating using near-critical and supercritical antisolvents
US5934289A (en) 1996-10-22 1999-08-10 Philip Morris Incorporated Electronic smoking system
US6290986B1 (en) 1996-10-24 2001-09-18 Pharmaceutical Applications Associates, Llc Method and composition for transdermal administration of pharmacologic agents
US6479074B2 (en) 1996-10-24 2002-11-12 Pharmaceutical Applications Associates Llc Methods and transdermal compositions for pain relief
US6694975B2 (en) 1996-11-21 2004-02-24 Aradigm Corporation Temperature controlling device for aerosol drug delivery
US5878752A (en) 1996-11-25 1999-03-09 Philip Morris Incorporated Method and apparatus for using, cleaning, and maintaining electrical heat sources and lighters useful in smoking systems and other apparatuses
US5744469A (en) 1996-11-26 1998-04-28 Eli Lilly And Company Method for treating dermatitis
CA2222830C (en) 1996-12-02 2004-03-30 Fisher & Paykel Limited Humidifier sleep apnea treatment apparatus
US5845933A (en) 1996-12-24 1998-12-08 Autoliv Asp, Inc. Airbag inflator with consumable igniter tube
WO1998029110A3 (en) 1996-12-30 1999-04-15 Battelle Memorial Institute Formulation and method for treating neoplasms by inhalation
US5819731A (en) 1997-01-03 1998-10-13 Minnesota Mining And Manufacturing Company Face mask having a combination adjustable ear loop and drop down band
US5855913A (en) 1997-01-16 1999-01-05 Massachusetts Instite Of Technology Particles incorporating surfactants for pulmonary drug delivery
EP1014943B1 (en) 1997-02-05 2002-06-19 Jago Research Ag Medical aerosol formulations
US6126919A (en) 1997-02-07 2000-10-03 3M Innovative Properties Company Biocompatible compounds for pharmaceutical drug delivery systems
US6051257A (en) 1997-02-24 2000-04-18 Superior Micropowders, Llc Powder batch of pharmaceutically-active particles and methods for making same
US5829435A (en) 1997-02-24 1998-11-03 Aradigm Corporation Prefilter for prevention of clogging of a nozzle in the generation of an aerosol and prevention of administration of undesirable particles
US6192882B1 (en) 1997-02-24 2001-02-27 Aradigm Corporation Formulation and devices for monitoring the efficacy of the delivery of aerosols
US5837713A (en) 1997-02-26 1998-11-17 Mayo Foundation For Medical Education And Research Treatment of eosinophil-associated pathologies by administration of topical anesthetics and glucocorticoids
US5769621A (en) * 1997-05-23 1998-06-23 The Regents Of The University Of California Laser ablation based fuel ignition
US5907075A (en) 1997-06-11 1999-05-25 The University Of Kansas Solid acid supercritical alkylation reactions using carbon dioxide and/or other co-solvents
US5906811A (en) 1997-06-27 1999-05-25 Thione International, Inc. Intra-oral antioxidant preparations
US5928520A (en) 1997-07-16 1999-07-27 Abanaki Corporation Method and apparatus for extracting ground water contaiminants
DE69804385T2 (en) 1997-07-23 2002-11-07 Japan Tobacco Inc Aroma-producing device
WO1999004797A1 (en) 1997-07-24 1999-02-04 EGIS Gyógyszergyár Rt. Use of 2,3-benzodiazepine derivatives for the preparation of pharmaceutical compositions to treat diseases connected with the endogenous opioid system
US6090212A (en) 1997-08-15 2000-07-18 Micro C Technologies, Inc. Substrate platform for a semiconductor substrate during rapid high temperature processing and method of supporting a substrate
US5855564A (en) 1997-08-20 1999-01-05 Aradigm Corporation Aerosol extrusion mechanism
US6250301B1 (en) 1997-08-28 2001-06-26 Hortal Harm B.V. Vaporizer for inhalation and method for extraction of active ingredients from a crude natural product or other matrix
DE69813853T3 (en) 1997-09-29 2011-05-12 Novartis Ag Perforated microparticles and their use
US6403597B1 (en) 1997-10-28 2002-06-11 Vivus, Inc. Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation
US6391282B1 (en) 1997-11-10 2002-05-21 Flemington Pharmaceutical Corp. Antihistamine sprays and ointments for relief of delayed contact dermatitis
DE19881732D2 (en) 1997-11-12 2000-08-24 Bayer Ag 2-phenyl-substituted imidazotriazinones as inhibitors Phoshodiesterase
US6014972A (en) 1997-12-11 2000-01-18 Thayer Medical Corporation Dry drug particle delivery system and method for ventilator circuits
US6062210A (en) * 1998-02-04 2000-05-16 Clifford G. Welles Portable heat generating device
US5900249A (en) 1998-02-09 1999-05-04 Smith; David J. Multicomponent pain relief topical medication
US6044777A (en) 1998-02-09 2000-04-04 Walsh; Michael J. Composite metal safe and method of making
FR2774684B1 (en) * 1998-02-10 2000-03-03 Poudres & Explosifs Ste Nale New non detonatable pyrotechnic materials for microsystems
KR20010041623A (en) 1998-03-05 2001-05-25 니뽄 신야쿠 가부시키가이샤 Fat emulsions for inhalational administration
US6168661B1 (en) * 1998-04-10 2001-01-02 Johnson Controls Technology Company Battery cell coating apparatus and method
WO1999052519A3 (en) 1998-04-14 1999-12-02 Gen Hospital Corp Methods for treating neuropsychiatric disorders
GB9810126D0 (en) 1998-05-13 1998-07-08 Glaxo Group Ltd
GB9810559D0 (en) 1998-05-15 1998-07-15 Bradford Particle Design Ltd Method and apparatus for particle formation
US6211171B1 (en) 1998-05-19 2001-04-03 Dalhousie University Use of antidepressants for local analgesia
US6014970A (en) 1998-06-11 2000-01-18 Aerogen, Inc. Methods and apparatus for storing chemical compounds in a portable inhaler
US6095153A (en) 1998-06-19 2000-08-01 Kessler; Stephen B. Vaporization of volatile materials
ES2221733T3 (en) 1998-06-22 2005-01-01 Pfizer Ireland Pharmaceuticals Intranasal formulations to treat sexual disorders.
US6241969B1 (en) 1998-06-26 2001-06-05 Elan Corporation Plc Aqueous compositions containing corticosteroids for nasal and pulmonary delivery
GB9814172D0 (en) 1998-06-30 1998-08-26 Andaris Ltd Formulation for inhalation
US6131570A (en) 1998-06-30 2000-10-17 Aradigm Corporation Temperature controlling device for aerosol drug delivery
EP1987854A1 (en) * 1998-07-14 2008-11-05 Altea Therapeutics Corporation Controlled removal of biological membrane by pyrotechnic charge for transmembrane transport
WO2000019991A1 (en) 1998-10-02 2000-04-13 Battelle Memorial Institute Inhalation chemotherapy for prevention and treatment of metastatic tumors in the lung
US6234167B1 (en) * 1998-10-14 2001-05-22 Chrysalis Technologies, Incorporated Aerosol generator and methods of making and using an aerosol generator
US6509005B1 (en) 1998-10-27 2003-01-21 Virginia Commonwealth University Δ9 Tetrahydrocannabinol (Δ9 THC) solution metered dose inhaler
US6255334B1 (en) 1998-10-30 2001-07-03 Pfizer Inc 5HT 1 receptor agonists and metoclopramide for the treatment of migraine
US7521068B2 (en) 1998-11-12 2009-04-21 Elan Pharma International Ltd. Dry powder aerosols of nanoparticulate drugs
JP2002529393A (en) 1998-11-12 2002-09-10 フランク ジー. ピルキーウィッツ, Inhalation system
DE19854007C2 (en) 1998-11-12 2001-05-17 Reemtsma H F & Ph System for providing an inhalable aerosol
DE19854009C2 (en) 1998-11-12 2001-04-26 Reemtsma H F & Ph System for providing an inhalable aerosol
DE19854012C2 (en) 1998-11-12 2001-05-10 Reemtsma H F & Ph System for providing an inhalable aerosol
EP1283036B1 (en) 1998-11-13 2008-01-02 Jagotec AG Multidosis dry powder inhaler with powder reservoir
WO2000029167A1 (en) 1998-11-16 2000-05-25 Aradigm Corporation Method of fabricating porous membrane with unique pore structure for aerosolized delivery of drugs
US6070575A (en) 1998-11-16 2000-06-06 Aradigm Corporation Aerosol-forming porous membrane with certain pore structure
US6113795A (en) 1998-11-17 2000-09-05 The University Of Kansas Process and apparatus for size selective separation of micro- and nano-particles
JP3506618B2 (en) 1998-11-18 2004-03-15 ウシオ電機株式会社 Incandescent bulb yellow light radiation
WO2000035417A1 (en) 1998-12-11 2000-06-22 Pharmachemie B.V. Pharmaceutical preparation for inhalation of an opioid
EP1313426A2 (en) 1998-12-24 2003-05-28 Bristol-Myers Squibb Pharma Company Succinoylamino benzodiazepines as inhibitors of a-beta protein production
CA2356267A1 (en) 1999-01-27 2000-08-03 Wyeth Holdings Corporation 2,3,4,5-tetrahydro-1h-¬1,4|benzodiazepine-3-hydroxamic acid as matrix metalloproteinase inhibitors
DE69901284D1 (en) 1999-01-27 2002-05-23 Idea Ag Transnasal transport or vaccination with hochadaptierbaren carriers
US6376550B1 (en) 1999-02-09 2002-04-23 Asta Medica Ag Pharmaceutical compositions containing tramadol for migraine
WO2000047203A9 (en) 1999-02-12 2001-09-07 Mqs Inc Formulation and system for intra-oral delivery of pharmaceutical agents
US6591839B2 (en) 1999-02-17 2003-07-15 Dieter Meyer Filter material for reducing harmful substances in tobacco smoke
FR2790078B1 (en) 1999-02-18 2004-11-26 Livbag Snc Electro-pyrotechnic igniter has strengthened security of ignition
US6444326B1 (en) 1999-03-05 2002-09-03 Restek Corporation Surface modification of solid supports through the thermal decomposition and functionalization of silanes
WO2000051491A1 (en) 1999-03-05 2000-09-08 Battelle Memorial Institute Method for safely and effectively administering a drug by inhalation
JP2002543092A (en) 1999-04-27 2002-12-17 イーライ・リリー・アンド・カンパニー Pulmonary administration for insulin crystals
CA2372150C (en) 1999-04-30 2011-08-30 The Regents Of The University Of Michigan Therapeutic applications of pro-apoptotic benzodiazepines
CA2370853C (en) 1999-05-03 2007-07-10 Battelle Memorial Institute Compositions for aerosolization and inhalation
US6428769B1 (en) 1999-05-04 2002-08-06 Aradigm Corporation Acute testosterone administration
DK1180020T4 (en) 1999-05-27 2009-10-05 Acusphere Inc Poröse Drug and processes for the preparation thereof
WO2000076673A1 (en) 1999-06-11 2000-12-21 Aradigm Corporation Method for producing an aerosol
WO2001095903A1 (en) 2000-06-15 2001-12-20 Respiratorius Ab 5-ht3 receptor antagonists for treatment of disorders involving airway constriction
US6413582B1 (en) * 1999-06-30 2002-07-02 General Electric Company Method for forming metallic-based coating
US20020061281A1 (en) 1999-07-06 2002-05-23 Osbakken Robert S. Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis
JP4999245B2 (en) 1999-07-16 2012-08-15 アラディグム コーポレイション System in order to achieve a non smoking
US6485780B1 (en) * 1999-08-23 2002-11-26 General Electric Company Method for applying coatings on substrates
CA2381425A1 (en) 1999-08-24 2001-03-01 Cellgate, Inc. Enhancing drug delivery across and into epithelial tissues using oligo arginine moieties
JP2003508502A (en) 1999-09-07 2003-03-04 コンジュケム,インコーポレーテッド Methods and compositions for the production of long-lived anti-tumor agent
JP2003509142A (en) 1999-09-15 2003-03-11 アラダイム コーポレーション Vacuum aerosol Kaana structure
EP1224187B1 (en) 1999-09-30 2006-02-22 Neurogen Corporation Certain alkylene diamine-substituted heterocycles
CA2386974C (en) 1999-10-15 2009-10-13 Geo Adam Benzodiazepine derivatives for use in acute or chronic neurological disorders
US6298784B1 (en) * 1999-10-27 2001-10-09 Talley Defense Systems, Inc. Heat transfer delay
ES2254164T3 (en) 1999-10-29 2006-06-16 Nektar Therapeutics Dry powder compositions with improved dispersibility.
WO2001041732A1 (en) 1999-12-06 2001-06-14 Gore Stanley L Compositions and methods for intranasal delivery of active agents to the brain
DE19961300A1 (en) 1999-12-18 2001-06-21 Asta Medica Ag Storage system for drugs in powder form and therefore equipped inhaler
US6324979B1 (en) 1999-12-20 2001-12-04 Vishay Intertechnology, Inc. Electro-pyrotechnic initiator
US6267110B1 (en) * 2000-02-25 2001-07-31 Convenience Heating Technologies Ltd. Disposable heating unit for food containers
ES2305057T3 (en) 2000-02-28 2008-11-01 Pharmakodex Limited Device for oral drug delivery.
US6443151B1 (en) 2000-03-08 2002-09-03 Aradigm Corporation Fluid velocity-sensitive trigger mechanism
WO2001069136A1 (en) * 2000-03-10 2001-09-20 The Regents Of The University Of California Laser ignition
US6632047B2 (en) 2000-04-14 2003-10-14 Board Of Regents, The University Of Texas System Heater element for use in an in situ thermal desorption soil remediation system
JP2001299916A (en) 2000-04-18 2001-10-30 Kao Corp Mask-shaped inhalator
US6551617B1 (en) 2000-04-20 2003-04-22 Bristol-Myers Squibb Company Taste masking coating composition
WO2001080895A3 (en) 2000-04-26 2002-08-08 First Horizon Pharmaceutical C Methods and compositions for the treatment of cardiac indications
EP1276672B1 (en) 2000-04-27 2007-11-21 Philip Morris USA Inc. Apparatus for generating an aerosol
WO2001093846A3 (en) 2000-05-23 2002-05-23 Exhale Therapeutics Inc Method for treating respiratory disorders associated with pulmonary elastic fiber injury comprising the use of clycosaminoglycans
US20020000225A1 (en) * 2000-06-02 2002-01-03 Carlos Schuler Lockout mechanism for aerosol drug delivery devices
GB0015981D0 (en) 2000-06-29 2000-08-23 Glaxo Group Ltd Novel process for preparing crystalline particles
FR2812545B1 (en) 2000-08-03 2003-03-28 Air Liquide Sante Int Aerosol inhalable medicated in the treatment or prevention of sweetness
JP4428835B2 (en) * 2000-08-09 2010-03-10 昭和電工株式会社 The magnetic recording medium and a manufacturing method thereof
US6613308B2 (en) 2000-09-19 2003-09-02 Advanced Inhalation Research, Inc. Pulmonary delivery in treating disorders of the central nervous system
US6514482B1 (en) 2000-09-19 2003-02-04 Advanced Inhalation Research, Inc. Pulmonary delivery in treating disorders of the central nervous system
US6478903B1 (en) 2000-10-06 2002-11-12 Ra Brands, Llc Non-toxic primer mix
US20020117175A1 (en) 2000-10-27 2002-08-29 Kottayil S. George Thermal vaporizing device for drug delivery
US6630462B2 (en) 2000-11-17 2003-10-07 Adolor Corporation Delta agonist analgesics
US6799572B2 (en) 2000-12-22 2004-10-05 Chrysalis Technologies Incorporated Disposable aerosol generator system and methods for administering the aerosol
US6491233B2 (en) 2000-12-22 2002-12-10 Chrysalis Technologies Incorporated Vapor driven aerosol generator and method of use thereof
US6701921B2 (en) * 2000-12-22 2004-03-09 Chrysalis Technologies Incorporated Aerosol generator having heater in multilayered composite and method of use thereof
US6443152B1 (en) 2001-01-12 2002-09-03 Becton Dickinson And Company Medicament respiratory delivery device
US7594507B2 (en) 2001-01-16 2009-09-29 Hewlett-Packard Development Company, L.P. Thermal generation of droplets for aerosol
FI20010115A0 (en) 2001-01-18 2001-01-18 Orion Corp Process for the preparation of nanoparticles
US6680668B2 (en) 2001-01-19 2004-01-20 Vishay Intertechnology, Inc. Fast heat rise resistor using resistive foil
WO2002074247A8 (en) 2001-03-19 2003-01-03 Praecis Pharm Inc Pharmaceutical formulations for sustained release
GB0108930D0 (en) 2001-04-10 2001-05-30 Boots Co Plc Therapeutic agents
US20030004142A1 (en) 2001-04-18 2003-01-02 Prior Christopher P. Use of NSAIDs for prevention and treatment of cellular abnormalities of the lung or bronchial pathway
US20070122353A1 (en) * 2001-05-24 2007-05-31 Hale Ron L Drug condensation aerosols and kits
US7090830B2 (en) 2001-05-24 2006-08-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7498019B2 (en) 2001-05-24 2009-03-03 Alexza Pharmaceuticals, Inc. Delivery of compounds for the treatment of headache through an inhalation route
WO2002094232A1 (en) 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Delivery of antidepressants through an inhalation route
US7645442B2 (en) 2001-05-24 2010-01-12 Alexza Pharmaceuticals, Inc. Rapid-heating drug delivery article and method of use
WO2002094234A1 (en) 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Delivery of opioids through an inhalation route
EP1392262A1 (en) * 2001-05-24 2004-03-03 Alexza Molecular Delivery Corporation Delivery of drug esters through an inhalation route
US7585493B2 (en) * 2001-05-24 2009-09-08 Alexza Pharmaceuticals, Inc. Thin-film drug delivery article and method of use
CA2641760A1 (en) * 2001-05-24 2002-11-28 Alexza Pharmaceuticals, Inc. Delivery of alprazolam, estazolam, midazolam or triazolam through an inhalation route
WO2002094244A3 (en) * 2001-05-24 2003-01-16 Alexza Molecular Delivery Corp Delivery of benzodiazepines through an inhalation route
US20080038363A1 (en) 2001-05-24 2008-02-14 Zaffaroni Alejandro C Aerosol delivery system and uses thereof
US6759029B2 (en) * 2001-05-24 2004-07-06 Alexza Molecular Delivery Corporation Delivery of rizatriptan and zolmitriptan through an inhalation route
US20030051728A1 (en) 2001-06-05 2003-03-20 Lloyd Peter M. Method and device for delivering a physiologically active compound
ES2271269T3 (en) 2001-06-19 2007-04-16 Norbert Muller Use of cox-2 inhibitors for the treatment of schizophrenia or tic disorders.
US6638981B2 (en) 2001-08-17 2003-10-28 Epicept Corporation Topical compositions and methods for treating pain
US6640801B2 (en) * 2001-08-29 2003-11-04 Tempra Technology, Inc. Heat pack with expansion capability
WO2003024456A1 (en) 2001-09-20 2003-03-27 Eisai Co., Ltd. Methods for treating and preventing migraines
US6568390B2 (en) * 2001-09-21 2003-05-27 Chrysalis Technologies Incorporated Dual capillary fluid vaporizing device
US6709537B2 (en) * 2001-10-05 2004-03-23 Autoliv Asp, Inc, Low firing energy initiator pyrotechnic mixture
US7814871B2 (en) * 2001-10-13 2010-10-19 Team Holdings Limited Self-priming portable device
US20030118512A1 (en) * 2001-10-30 2003-06-26 Shen William W. Volatilization of a drug from an inclusion complex
US6779520B2 (en) 2001-10-30 2004-08-24 Iep Pharmaceutical Devices Inc. Breath actuated dry powder inhaler
GB0126150D0 (en) 2001-10-31 2002-01-02 Gw Pharma Ltd A device method and resistive element for vaporising a substance
WO2003041693A1 (en) * 2001-11-09 2003-05-22 Alexza Molecular Delivery Corporation Delivery of diazepam through an inhalation route
US7078016B2 (en) 2001-11-21 2006-07-18 Alexza Pharmaceuticals, Inc. Delivery of caffeine through an inhalation route
CA2462576A1 (en) 2001-11-21 2003-06-03 Alexza Molecular Delivery Corporation Open-celled substrates for drug delivery
US6804458B2 (en) 2001-12-06 2004-10-12 Chrysalis Technologies Incorporated Aerosol generator having heater arranged to vaporize fluid in fluid passage between bonded layers of laminate
US20030106551A1 (en) 2001-12-06 2003-06-12 Sprinkel F. Murphy Resistive heater formed inside a fluid passage of a fluid vaporizing device
CN1176075C (en) 2001-12-07 2004-11-17 北京燕山石油化工公司研究院 Pyrrole derivatives preparation method
US20030138508A1 (en) 2001-12-18 2003-07-24 Novack Gary D. Method for administering an analgesic
US6701922B2 (en) 2001-12-20 2004-03-09 Chrysalis Technologies Incorporated Mouthpiece entrainment airflow control for aerosol generators
US6772756B2 (en) 2002-02-09 2004-08-10 Advanced Inhalation Revolutions Inc. Method and system for vaporization of a substance
US6804118B2 (en) 2002-03-15 2004-10-12 Delphi Technologies, Inc. Thermal dissipation assembly for electronic components
CA2483687A1 (en) 2002-05-13 2003-11-20 Alexza Molecular Delivery Corporation Delivery of drug amines through an inhalation route
US7458374B2 (en) * 2002-05-13 2008-12-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
JP4148705B2 (en) 2002-06-19 2008-09-10 松下電器産業株式会社 Analysis equipment
WO2004011396A3 (en) 2002-07-29 2012-02-02 The Regents Of The University Of California Lead-free electric match compositions
JP4933046B2 (en) 2002-09-06 2012-05-16 フィリップ モーリス ユーエスエー インコーポレイテッド Liquid aerosol formulations, aerosol generator and aerosol generating methods
US6772757B2 (en) 2002-10-25 2004-08-10 Chrysalis Technologies Incorporated Concentric controlled temperature profile fluid vaporizing device
US6739264B1 (en) 2002-11-04 2004-05-25 Key Safety Systems, Inc. Low cost ignition device for gas generators
WO2004047841A1 (en) 2002-11-26 2004-06-10 Alexza Molecular Delivery Corporation Treatment of headache with antipsychotics delivered by inhalation
US7550133B2 (en) * 2002-11-26 2009-06-23 Alexza Pharmaceuticals, Inc. Respiratory drug condensation aerosols and methods of making and using them
US20040105818A1 (en) * 2002-11-26 2004-06-03 Alexza Molecular Delivery Corporation Diuretic aerosols and methods of making and using them
DK1567164T3 (en) * 2002-11-26 2009-05-18 Alexza Pharmaceuticals Inc Use of Loxapine for the manufacture of a medicament for the treatment of pain
US20060193788A1 (en) 2002-11-26 2006-08-31 Hale Ron L Acute treatment of headache with phenothiazine antipsychotics
US7913688B2 (en) * 2002-11-27 2011-03-29 Alexza Pharmaceuticals, Inc. Inhalation device for producing a drug aerosol
US20040162517A1 (en) 2002-12-04 2004-08-19 Otto Furst Needleless hydpodermic injection device with non-electric ignition means
DE10256775A1 (en) 2002-12-05 2004-06-24 Lts Lohmann Therapie-Systeme Ag Preparation of film forming composition for transmucosal delivery of nicotine used for treating tobacco addiction, includes converting nicotine free base to its salt with acid and/or incorporation of nicotine as salt
US7229966B2 (en) 2002-12-17 2007-06-12 Nastech Pharmaceutical Company Inc. Compositions and methods for enhanced mucosal delivery of Y2 receptor-binding peptides and methods for treating and preventing obesity
FR2852517B1 (en) 2003-03-21 2005-11-11 Device for needleless injection has pyrotechnic cartridge and method for assembling such a device
EP1625333A1 (en) 2003-05-21 2006-02-15 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
GB0312433D0 (en) 2003-05-30 2003-07-09 Qinetiq Nanomaterials Ltd Devices
JP2005034021A (en) * 2003-07-17 2005-02-10 Seiko Epson Corp Electronic cigarette
WO2005014090A1 (en) * 2003-08-04 2005-02-17 Alexza Pharmaceuticals, Inc. Methods of determining film thicknesses for an aerosol delivery article
CA2534566A1 (en) 2003-08-04 2005-02-24 Alexza Pharmaceuticals, Inc. Substrates for drug delivery device and methods of preparing and use
JP4411901B2 (en) 2003-08-11 2010-02-10 セイコーエプソン株式会社 Atomizing device
EP1703932A1 (en) * 2003-12-15 2006-09-27 Alexza Molecular Delivery Corporation Treatment of breakthrough pain by drug aerosol inhalation
US20050131739A1 (en) * 2003-12-16 2005-06-16 Alexza Molecular Delivery Corporation Methods for monitoring severity of panic attacks and other rapidly evolving medical events in real time
US7402777B2 (en) 2004-05-20 2008-07-22 Alexza Pharmaceuticals, Inc. Stable initiator compositions and igniters
US7540286B2 (en) 2004-06-03 2009-06-02 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
CA2576961A1 (en) 2004-08-12 2006-03-02 Alexza Pharmaceuticals, Inc. Aerosol drug delivery device incorporating percussively activated heat packages
US20100006092A1 (en) 2004-08-12 2010-01-14 Alexza Pharmaceuticals, Inc. Aerosol Drug Delivery Device Incorporating Percussively Activated Heat Packages
US20060032496A1 (en) * 2004-08-12 2006-02-16 Alexza Molecular Delivery Corporation Inhalation actuated percussive ignition system
US20060051824A1 (en) 2004-09-03 2006-03-09 Haoyun An Tetrahydrocannabinoid antigens and method of use
WO2006044421A3 (en) * 2004-10-12 2006-08-03 Alexza Pharmaceuticals Inc Cardiac safe, rapid medication delivery
US7494344B2 (en) 2005-12-29 2009-02-24 Molex Incorporated Heating element connector assembly with press-fit terminals
US20080299048A1 (en) 2006-12-22 2008-12-04 Alexza Pharmaceuticals, Inc. Mixed drug aerosol compositions
US7513781B2 (en) 2006-12-27 2009-04-07 Molex Incorporated Heating element connector assembly with insert molded strips
US20080216828A1 (en) 2007-03-09 2008-09-11 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
WO2008134668A3 (en) 2007-04-27 2009-04-16 Alexza Pharmaceuticals Inc Heat-labile prodrugs
US20090180968A1 (en) 2008-01-11 2009-07-16 Alexza Pharmaceuticals, Inc. Metal Coordination Complexes Of Volatile Drugs
US20100065052A1 (en) 2008-09-16 2010-03-18 Alexza Pharmaceuticals, Inc. Heating Units
US7834295B2 (en) 2008-09-16 2010-11-16 Alexza Pharmaceuticals, Inc. Printable igniters
US20100068155A1 (en) 2008-09-16 2010-03-18 Alexza Pharmaceuticals, Inc. Reactant Formulations and Methods for Controlled Heating
US20100300433A1 (en) 2009-05-28 2010-12-02 Alexza Pharmaceuticals, Inc. Substrates for Enhancing Purity or Yield of Compounds Forming a Condensation Aerosol
GB0910537D0 (en) * 2009-06-18 2009-07-29 Ivax Pharmaceuticals Ireland Inhaler
US20100181387A1 (en) 2009-12-01 2010-07-22 Zaffaroni Alejandro C Aerosol delivery system and uses thereof
US20120048963A1 (en) 2010-08-26 2012-03-01 Alexza Pharmaceuticals, Inc. Heat Units Using a Solid Fuel Capable of Undergoing an Exothermic Metal Oxidation-Reduction Reaction Propagated without an Igniter

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3830671A (en) * 1972-11-30 1974-08-20 American Metal Climax Inc Thermally ignitable zirconium-plastic composition
US4096549A (en) * 1976-11-09 1978-06-20 Gte Sylvania Incorporated Multilamp photoflash assembly
US4193388A (en) * 1978-04-19 1980-03-18 Nasa Portable heatable container
US5322018A (en) * 1991-11-27 1994-06-21 The Ensign-Bickford Company Surface-initiating deflagrating material
US6497780B1 (en) * 1999-06-09 2002-12-24 Steven A. Carlson Methods of preparing a microporous article
US6289889B1 (en) * 1999-07-12 2001-09-18 Tda Research, Inc. Self-heating flexible package
US6506454B2 (en) * 2000-03-07 2003-01-14 Koito Manufacturing Co., Ltd. Part painting method
US20030037437A1 (en) * 2001-05-08 2003-02-27 General Electric System for applying a diffusion aluminide coating on a selective area of a turbine engine component
US6993811B2 (en) * 2001-05-08 2006-02-07 General Electric Company System for applying a diffusion aluminide coating on a selective area of a turbine engine component

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7988952B2 (en) 2001-05-24 2011-08-02 Alexza Pharmaceuticals, Inc. Delivery of drug esters through an inhalation route
US9211382B2 (en) 2001-05-24 2015-12-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US8173107B2 (en) 2001-05-24 2012-05-08 Alexza Pharmaceuticals, Inc. Delivery of antipsychotics through an inhalation route
US9440034B2 (en) 2001-05-24 2016-09-13 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7645442B2 (en) 2001-05-24 2010-01-12 Alexza Pharmaceuticals, Inc. Rapid-heating drug delivery article and method of use
US8235037B2 (en) 2001-05-24 2012-08-07 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US20060257329A1 (en) * 2001-05-24 2006-11-16 Alexza Pharmaceuticals, Inc. Delivery of drug esters through an inhalation route
US9439907B2 (en) 2001-06-05 2016-09-13 Alexza Pharmaceutical, Inc. Method of forming an aerosol for inhalation delivery
US9687487B2 (en) 2001-06-05 2017-06-27 Alexza Pharmaceuticals, Inc. Aerosol forming device for use in inhalation therapy
US8074644B2 (en) 2001-06-05 2011-12-13 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US9308208B2 (en) 2001-06-05 2016-04-12 Alexza Pharmaceuticals, Inc. Aerosol generating method and device
US7942147B2 (en) 2001-06-05 2011-05-17 Alexza Pharmaceuticals, Inc. Aerosol forming device for use in inhalation therapy
US8955512B2 (en) 2001-06-05 2015-02-17 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US7987846B2 (en) 2002-05-13 2011-08-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US8003080B2 (en) 2002-05-13 2011-08-23 Alexza Pharmaceuticals, Inc. Delivery of drug amines through an inhalation route
US8288372B2 (en) 2002-11-26 2012-10-16 Alexza Pharmaceuticals, Inc. Method for treating headache with loxapine
US8506935B2 (en) 2002-11-26 2013-08-13 Alexza Pharmaceuticals, Inc. Respiratory drug condensation aerosols and methods of making and using them
US7981401B2 (en) 2002-11-26 2011-07-19 Alexza Pharmaceuticals, Inc. Diuretic aerosols and methods of making and using them
US7913688B2 (en) 2002-11-27 2011-03-29 Alexza Pharmaceuticals, Inc. Inhalation device for producing a drug aerosol
US9370629B2 (en) 2003-05-21 2016-06-21 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US8387612B2 (en) 2003-05-21 2013-03-05 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US8991387B2 (en) 2003-05-21 2015-03-31 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US7923662B2 (en) 2004-05-20 2011-04-12 Alexza Pharmaceuticals, Inc. Stable initiator compositions and igniters
US8333197B2 (en) 2004-06-03 2012-12-18 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
US20070196666A1 (en) * 2005-07-11 2007-08-23 The Regents Of The University Of California Electrical initiation of an energetic nanolaminate film
US7687746B2 (en) 2005-07-11 2010-03-30 Lawrence Livermore National Security, Llc Electrical initiation of an energetic nanolaminate film
US20100162913A1 (en) * 2006-05-18 2010-07-01 The Regents Of The University Of California Energetic composite and system with enhanced mechanical sensitivity to initiation of self-sustained reaction
US8187398B2 (en) * 2006-05-18 2012-05-29 Lawrence Livermore National Security, Llc Energetic composite and system with enhanced mechanical sensitivity to initiation of self-sustained reaction
US20080073558A1 (en) * 2006-09-25 2008-03-27 Philip Morris Usa Inc. Heat capacitor for capillary aerosol generator
US7518123B2 (en) * 2006-09-25 2009-04-14 Philip Morris Usa Inc. Heat capacitor for capillary aerosol generator
US20090050355A1 (en) * 2007-08-24 2009-02-26 World Properties, Inc. Thermoplastic Films For Insulated Metal Substrates And Methods Of Manufacture Thereof
US8069559B2 (en) * 2007-08-24 2011-12-06 World Properties, Inc. Method of assembling an insulated metal substrate
US7834295B2 (en) 2008-09-16 2010-11-16 Alexza Pharmaceuticals, Inc. Printable igniters
WO2013128176A1 (en) * 2012-02-28 2013-09-06 British American Tobacco (Investments) Limited Delivery devices and units therefor
US9063041B2 (en) 2012-11-30 2015-06-23 General Electric Company Device and method for drying biological sample on substrate
US9724341B2 (en) 2013-07-11 2017-08-08 Alexza Pharmaceuticals, Inc. Nicotine salt with meta-salicylic acid
EP3049733A4 (en) * 2014-08-01 2017-03-22 Andrea Rossi Fluid heater
JP6145808B1 (en) * 2014-08-01 2017-06-14 ロッシ,アンドレROSSI, Andrea Fluid heater
JP2017523369A (en) * 2014-08-01 2017-08-17 ロッシ,アンドレROSSI, Andrea Fluid heater

Also Published As

Publication number Publication date Type
WO2004104491A3 (en) 2005-01-06 application
WO2004104491A2 (en) 2004-12-02 application
EP1625335A2 (en) 2006-02-15 application
CA2526470A1 (en) 2004-12-02 application
EP1625336A2 (en) 2006-02-15 application
WO2004104490A1 (en) 2004-12-02 application
WO2004104492A2 (en) 2004-12-02 application
WO2004104490A9 (en) 2006-02-09 application
CA2526432A1 (en) 2004-12-02 application
JP2007516015A (en) 2007-06-21 application
WO2004104492A3 (en) 2005-01-27 application
EP1625336B9 (en) 2012-03-21 grant
ES2370395T3 (en) 2011-12-15 grant
CA2526478A1 (en) 2004-12-02 application
US8991387B2 (en) 2015-03-31 grant
US20150265783A1 (en) 2015-09-24 application
EP1625336B1 (en) 2011-08-17 grant
EP1625333A1 (en) 2006-02-15 application
US9370629B2 (en) 2016-06-21 grant
JP2007516403A (en) 2007-06-21 application
US8387612B2 (en) 2013-03-05 grant
EP1625334B1 (en) 2011-05-18 grant
JP2007516404A (en) 2007-06-21 application
EP2096374A3 (en) 2012-01-25 application
EP1625334A2 (en) 2006-02-15 application
US20040234916A1 (en) 2004-11-25 application
EP2096374A2 (en) 2009-09-02 application
US20090301363A1 (en) 2009-12-10 application
WO2004104493A3 (en) 2005-02-17 application
US20130180516A1 (en) 2013-07-18 application
EP1625334B9 (en) 2012-07-25 grant
US20040234914A1 (en) 2004-11-25 application
US20050079166A1 (en) 2005-04-14 application
CA2526475A1 (en) 2004-12-02 application
WO2004104493A2 (en) 2004-12-02 application
JP2007516149A (en) 2007-06-21 application
JP4601619B2 (en) 2010-12-22 grant

Similar Documents

Publication Publication Date Title
US4913168A (en) Flavor delivery article
US6340472B1 (en) Method for reducing onset time of pharmaceutically active compounds
US7078016B2 (en) Delivery of caffeine through an inhalation route
US7290549B2 (en) Chemical heat source for use in smoking articles
US5957124A (en) Dynamic particle size control for aerosolized drug delivery
US7540286B2 (en) Multiple dose condensation aerosol devices and methods of forming condensation aerosols
US5743251A (en) Aerosol and a method and apparatus for generating an aerosol
US20110226236A1 (en) Inhaler
US20130312742A1 (en) Low temperature electronic vaporization device and methods
US6737042B2 (en) Delivery of drug esters through an inhalation route
US6640050B2 (en) Fluid vaporizing device having controlled temperature profile heater/capillary tube
US4917119A (en) Drug delivery article
US6098620A (en) Device for aerosolizing narcotics
US20020119186A1 (en) Controlled heat induced rapid delivery of pharmaceuticals from skin depot
ZIERENBERG Optimizing the in vitro performance of Respimat
US20080066741A1 (en) Methods and systems of delivering medication via inhalation
Ganderton General factors influencing drug delivery to the lung
US20140190496A1 (en) Methods and devices for compound delivery
US20050126562A1 (en) Treatment of breakthrough pain by drug aerosol inhalation
WO1996013291A1 (en) Device for aerosolizing narcotics
US20070256688A1 (en) Mechanical single dose intrapulmonary drug delivery devices
WO2005120614A1 (en) Multiple dose condensation aerosol devices and methods of forming condensation aerosols
US20080173300A1 (en) Portable vaporized substance delivery system
US20100258118A1 (en) Inhaler devices and bespoke pharmaceutical compositions
US20080078382A1 (en) Methods and Systems of Delivering Medication Via Inhalation

Legal Events

Date Code Title Description
AS Assignment

Owner name: ALEXZA MOLECULAR DELIVERY CORPORATION, CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:HALE, RON L.;QUINTANA, REYNALDO J.;SHARMA, KRISHNAMOHAN;AND OTHERS;REEL/FRAME:015379/0577

Effective date: 20040519

AS Assignment

Owner name: ALEXZA PHARMACEUTICALS, INC., CALIFORNIA

Free format text: CHANGE OF NAME;ASSIGNOR:ALEXZA MOLECULAR DELIVERY CORPORATION;REEL/FRAME:016926/0674

Effective date: 20050720

AS Assignment

Owner name: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF

Free format text: EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE;ASSIGNOR:ALEXZA PHARMACEUTICALS;REEL/FRAME:021615/0487

Effective date: 20070309