WO2023114341A1 - Dispositifs portatifs et procédés pour produire des aérosols à condensation d'apomorphine de haute pureté - Google Patents

Dispositifs portatifs et procédés pour produire des aérosols à condensation d'apomorphine de haute pureté Download PDF

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Publication number
WO2023114341A1
WO2023114341A1 PCT/US2022/052908 US2022052908W WO2023114341A1 WO 2023114341 A1 WO2023114341 A1 WO 2023114341A1 US 2022052908 W US2022052908 W US 2022052908W WO 2023114341 A1 WO2023114341 A1 WO 2023114341A1
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WO
WIPO (PCT)
Prior art keywords
drug
disposable cartridge
previous
foil substrate
handheld controller
Prior art date
Application number
PCT/US2022/052908
Other languages
English (en)
Inventor
Mingzhu LEI
Kyo KEUM
Tom ALFREDSON
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
Application filed by Alexza Pharmaceuticals, Inc. filed Critical Alexza Pharmaceuticals, Inc.
Publication of WO2023114341A1 publication Critical patent/WO2023114341A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/04—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
    • A61M11/041—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters
    • A61M11/042—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised using heaters electrical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
    • A61M15/0048—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged in a plane, e.g. on diskettes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/0015—Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors
    • A61M2016/0018—Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical
    • A61M2016/0021—Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical with a proportional output signal, e.g. from a thermistor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/003—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter
    • A61M2016/0033—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter electrical
    • A61M2016/0039—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter electrical in the inspiratory circuit
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0468—Liquids non-physiological

Definitions

  • the present methods and devices relate to the field of aerosol drug delivery devices, specifically to the field of devices for the precise administration of pure apomorphine condensation aerosols.
  • Apomorphine is a drug approved for the treatment of acute hypomobility or “off’ episodes in patients with Parkinson’s disease.
  • the most practiced clinically administered route for apomorphine is by intermittent sublingual administration (e.g. Kynmobi®), subcutaneous injection via a pre-filled injection pen (e.g. Apokyn®, or Apo-Go®), or by continuous infusion pump (e.g. Dacepton®).
  • Apomorphine has the following chemical structure: and chemical name (6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,l l-diol. Apomorphine is marketed as hydrochloride salt.
  • US2008311176 AA discloses that the thickness of the solid drug film in a thermal generating aerosol device influences the purity of the generated aerosol.
  • the slope of the regression line of the aerosol purity Vs. thickness is negative, meaning that the thicker the solid drug film, the less pure the aerosol. This can be seen in Table 1 of the US’ 176 A A and its related figures.
  • the slope ranges from -0.083 for mitazolam to -3.76 for sildenafil. There is no such data for apomorphine or any of its salts, only that the preferred solid drug film thickness for apomorphine is between 0.1 and 5 pm on a surface area of 4-200 cm 2 .
  • Document US’ 176 AA discloses that the desirable solid drug film thickness should be determined by an iterative process and that at least 50% of the total amount of drug composition contained in the solid drug film has to be vaporized.
  • WO2019152873 (WO’ 873) a disposable cartridge with a solid drug film coated on an electrically heated drug foil substrate is described.
  • the disposable cartridge can be connected to a handheld controller which includes the electronics and electrical components, including the electricity source.
  • the apomorphine emitted dose can be 20, 30, 40, 50, 60, 80, 90, or 95% of the deposited drug, i.e. almost the full range of percentage of emitted dose from the deposited drug and that the impurities increase when the temperature is between 260 °C and 400 °C.
  • condensation aerosols formation of condensation aerosols, drug delivery devices, drug composition film thickness (or solid drug film thickness), substrate area, aerosol particle size distribution (aPSD), mass median aerodynamic diameter (MMAD), analysis of drug-containing aerosols, other analytical methods, vaporization temperature control or drug foil substrate design can be found, inter alia, in the description and examples of WO2019152873, WO2017189883 or WO2016145075 which are incorporated by reference.
  • the patients with Parkinson’s disease may find difficulties in self-administering a subcutaneous injection, in correctly placing a sublingual film, or using an infusion pump during a hypomobility or “off’ episode. There is a need to provide an easy route of administration of apomorphine for such patients.
  • Such route of administration should be non-invasively and provide an easy treatment of “off’ episodes in Parkinson’s disease patients with fast onset of action and should provide apomorphine with high purity Summary
  • a handheld medical device suitable to generate an emitted dose of a drug condensation aerosol by thermal vaporization of a solid drug film (207) comprising: a. an airway (203) defined by internal walls; b. an air inlet (220) at one end of the airway (203); c. an air outlet (202), configured as a mouthpiece, at another end of the airway (203); d. a drug foil substrate (205) having an impermeable surface, with or without perforations, placed within the airway (203); e. a drug foil substrate support (204); and f. a solid drug film (207) coated on the drug foil substrate (205);
  • the content of drug in the solid drug film (207) is between 1.5 and 10 times the emitted dose
  • the drug is apomorphine, its pharmaceutically acceptable salts, its polymorphs, its prodrugs and/or combinations thereof.
  • a handheld controller comprising:
  • At least one microcontroller (102) configured to vaporize between 10 % and 80 % of the drug in the solid drug film (207) and produce drug condensation aerosol particles;
  • Another aspect is a disposable cartridge (200) comprising features a) to f) described above suitable to be connected to the handheld controller above.
  • Another aspect is a handheld medical device, disposable cartridge (200) or handheld controller (100) according to any of the preceding aspects for use in therapy.
  • Handheld medical device is a device which can be held and operated with one hand.
  • the handheld medical device includes all the elements required to be operated in one single device or these elements are separated into more than one device, e.g. into two devices, such as a disposable cartridge (200) and a handheld controller (100).
  • Disposable cartridge is understood to be a single dose or multidose cartridge comprising a drug coated on a drug foil substrate, an air inlet optionally that may or may not be connected to a handheld controller, an airway (203), an air outlet configured as a mouthpiece and connectors to electrically connect it to the handheld controller (100).
  • the disposable cartridge is attached to a handheld controller in order to be operated.
  • “Handheld controller” is a reusable device comprising at least one battery, connectors, electrical parts, and electronics suitable to heat the drug foil substrate once a disposable cartridge has been attached to it.
  • Electrodes are means to transfer electricity from a battery to a drug foil substrate, a microcontroller or a memory.
  • Data connections are means to transfer data between a microcontroller and any sensor or detector, or between a microcontroller and any memory, wherein the sensor or detector and memory are in the disposable cartridge and/or the handheld controller.
  • Battery means a device for storing energy in chemical compounds capable of generating an electrical current. It can be a rechargeable battery, such as nickel-metal hydride, lithium-polymer battery, or the like (see WO2019152873 for further details on rechargeable batteries); or a single use battery, such as a dry cell battery, alkaline batteries, silver cells batteries, zinc-air batteries, lithium batteries, nickel oxyhydroxide batteries and the like. When the heating to vaporize a drug is chemical heating the battery is needed to start the chemical reaction and/or control the electronics of the device.
  • a rechargeable battery such as nickel-metal hydride, lithium-polymer battery, or the like (see WO2019152873 for further details on rechargeable batteries); or a single use battery, such as a dry cell battery, alkaline batteries, silver cells batteries, zinc-air batteries, lithium batteries, nickel oxyhydroxide batteries and the like.
  • Air inlet controller extension is an extension of the airway of a disposable cartridge (200) in a handheld controller (100).
  • Pneumatic sealing is a piece, such a gasket or an O-ring, that helps joining two systems, e.g. ducts, and prevents air leakage.
  • Airway is defined by the device internal walls with an air outlet (202) configured as a mouthpiece at one end and one or more air inlets (220) at the other end.
  • the one or more airflow diverting structures and the one or more airflow straightening structures are placed within the airway.
  • Airflow is the movement or flow of air through the airway from the air inlet (220) to the air outlet (202).
  • Area density in a two-dimensional object is calculated as the mass per unit area.
  • Airflow detector is any sensor capable of detecting if the airflow is above a predetermined threshold value.
  • the airflow detector can be of any kind, such as a differential pressure sensor, a thermistor, an air flow or sail switch, a hot wire anemometer, or vane anemometer.
  • “Drug foil substrate” is an impermeable surface where a drug is deposited to be heated and aerosolized. If the heating is electric, further information on electric heating can be found in WO2019152873, incorporated herein by reference. If the heating is chemical, it may be referred to as chemical heating pack, further information on chemical heating packs can be found in W02004104492, incorporated herein by reference.
  • the drug foil substrate defines a “drug foil substrate plane” which in one embodiment is substantially parallel to the aerosol axis (223), i.e. defining an angle of -10 to 10°.
  • the drug foil substrate may be planar or curved.
  • Solid drug film is a layer which comprises a pure drug, two or more drugs, or one or more drugs in combination with additional components. Additional components can include, for example, pharmaceutically acceptable excipients, carriers, additives, surfactants, and the like.
  • Emitted dose is the amount of drug delivered to the patient when the cartridge is actuated. It is known as well as delivered dose.
  • Condensation aerosol refers to an aerosol that has been formed by the thermal vaporization of a solid drug film and subsequent cooling of the vapor, such that the vapor condenses to form particles.
  • Figure 1A illustrates a Device 1: SS, Electrical Bench-Top Screening Device.
  • Figure IB illustrates a Device 2: Handheld housing.
  • Figure 1C illustrates a Heat Source 1 : Testing electric heating.
  • Figure ID illustrates a Heat Source 2: Chemical heat package.
  • Figure IE illustrates a Heat Source 3: Electric heating.
  • FIG. 2A and 2B illustrate a handheld medical device including a disposable cartridge (200) and a handheld controller (100).
  • the air inlet (220) of the disposable cartridge is connected to the air inlet extension (103) of the handheld controller (100).
  • the air inlet (220) of the disposable cartridge is directly open to the atmosphere.
  • Figure 3A is a plot of the purity of the emitted aerosol versus the area density of the coated apomorphine HC1 of Example 1.
  • Figure 3B is a plot of the % vaporization of the emitted aerosol versus the area density of the coated apomorphine HC1 of Example 1.
  • Figure 4 is a plot of the purity of the emitted aerosol and % vaporization versus the temperature of the drug foil substrate of Comparative Example 1.
  • Figure 5 is a plot of the purity of the emitted aerosol and % vaporization versus the temperature of the drug foil substrate of Example 2.
  • FIG. 2A illustrates a handheld medical device comprising a disposable cartridge (200) attached to a handheld controller (100).
  • the disposable cartridge (200) comprises an air inlet (220), and airway (203) and an air outlet configured as a mouthpiece (202).
  • the handheld controller (100) comprises the drug foil substrate heating circuit including a battery (101), and a microcontroller (102); and an air inlet controller extension (103).
  • the air inlet controller extension (103) and the air inlet (220) are fluidly and tightly connected.
  • the handheld controller (100) and the disposable cartridge (200) are connected via an electric (302) and, optionally, a data interface (301) to share electricity and, optionally, data.
  • Figure 2B is similar to figure 2A but without the air inlet controller extension (103) in the handheld controller (100).
  • the air inlet (220) in the disposable cartridge (200), which may contain a baffle, is directly open to the atmosphere.
  • a method of implementing the current disclosure is to deposit onto the drug foil substrate the amount of drug desired for the emitted dose and find the right conditions for the evaporation of said amount of apomorphine, its pharmaceutically acceptable salts, its polymorphs, its prodrugs and/or combinations thereof.
  • a second step 1.5 to 10 times of apomorphine, its pharmaceutically acceptable salts, its polymorphs, its prodrugs and/or combinations thereof is deposited onto the drug foil substrate and the conditions are fine tuned. Numbered embodiments are described below.
  • a handheld medical device suitable to generate an emitted dose of a drug condensation aerosol by thermal vaporization of a solid drug film (207) comprising: a. an airway (203) defined by internal walls; b. an air inlet (220) at one end of the airway (203); c. an air outlet (202), configured as a mouthpiece, at another end of the airway (203); d. a drug foil substrate (205) having an impermeable surface, with or without perforations, placed within the airway (203); e. a drug foil substrate support (204); and f.
  • Embodiment 1 which comprises a disposable cartridge (200) and a handheld controller (100), wherein the disposable cartridge (200) is suitable to be connected to the handheld controller (100); the disposable cartridge (200) comprises features a) to f) according to Embodiment 1; and the handheld controller (100) and the disposable cartridge (200) comprise one or more connectors (302) to electrically connect each other.
  • the solid drug film (207) has an area density from 0.001 to 5 mg/cm 2 ; in another embodiment from 0.01 to 4 mg/cm 2 ; in another embodiment from 0.05 to 3 mg/cm 2 ; in another embodiment from 0.1 to 2 mg/cm 2 , in another embodiment from 0.15 to 2 mg/cm 2 , or in another embodiment from 0.25 to 1.5 mg/cm 2 .
  • the device or disposable cartridge (200) is configured to heat the drug foil substrate (205) between 200 and 400 °C; in another embodiment between 200 and 350 °C; in another embodiment between 250 and 375 °C; in another embodiment between 250 and 350 °C; in another embodiment between 260 and 400 °C; in another embodiment between 275 and 350 °C; or in another embodiment between 290 and 350 °C.
  • a handheld controller (100) suitable to be connected to the disposable cartridge according to any of the Embodiment 2 to Embodiment 17 or Embodiment 23 to Embodiment 25 comprising: a drug foil substrate (205) heating circuit; at least one battery (101); at least one microcontroller (102) configured to vaporize between 10 % and 80% of the drug in the solid drug film (207) and produce drug condensation aerosol particles; and one or more connectors (302) to electrically connect the handheld controller (100) to a disposable cartridge (200).
  • the handheld controller (100) according to the previous Embodiment, wherein the at least one microcontroller (102) is configured to vaporize between 12 % and 50 % of the drug in the solid drug film (207); in another embodiment between 14 % and 35 %; in another embodiment between 16 % and 29 %; or in another embodiment between 18 % and 25 %.
  • the handheld controller (100) according to any of the Embodiment 18 to Embodiment 19, which further comprises an air inlet controller extension.
  • the handheld controller (100) according to any of the Embodiment 18 to Embodiment 20, which further comprises an airflow detector which triggers the heating of the drug foil substrate (205).
  • the disposable cartridge (200) according to any of the Embodiment 23 to Embodiment 24, which is suitable to be data connected to the handheld controller (100).
  • the handheld controller (100) according to any of the Embodiment 26 to Embodiment 27, which is suitable to be data connected to the disposable cartridge (200).
  • a handheld medical device according to any of the preceding Embodiments, a disposable cartridge (200) according to any of the Embodiment 2 to Embodiment 17, or Embodiment 23 to Embodiment 25, or handheld controller (100) according to any of Embodiment 18 to Embodiment 22 or Embodiment 26 to Embodiment 28 for use in therapy.
  • a method of treatment for a condition or episode which comprises administering a drug included in the solid drug film (207) coated on at least a portion of the drug foil substrate (205) of the handheld medical device, disposable cartridge (200) or handheld controller (100) according to any of the Embodiment 1 to Embodiment 28, wherein the condition or episode is Parkinson’s disease, off-episodes in Parkinson’s disease, and/or idiopathic Parkinson’s disease.
  • the condition or episode is Parkinson’s disease, off-episodes in Parkinson’s disease, and/or idiopathic Parkinson’s disease.
  • the handheld medical device, disposable cartridge (200) or handheld controller (100) according to any of the Embodiment 1 to Embodiment 28 which comprises a drug included in the solid drug film coated on at least a portion of the drug foil substrate (205) for the manufacturing of a medicament for the treatment of a condition or episode; wherein the condition or episode is Parkinson’s disease, off-episodes in Parkinson’s disease, and/or idiopathic Parkinson’s disease.
  • a medicament comprising apomorphine, or its pharmaceutically acceptable salts for use in the handheld medical device or disposable cartridge (200) according to any of the Embodiment 1 to Embodiment 28.
  • a method of generating a condensation aerosol comprising heating the disposable cartridge (200) according to any of the Embodiment 2 to 17 to a temperature according to Embodiment 14 with the heating slope of Embodiment 15.
  • the solution is analysed by UPLC with water (ammonium formate/formic acid) and acetonitrile as mobile phases using UV detection at 275 nm as acquisition wavelength.
  • the mouthpiece of the device to be tested was tightly attached to a mouth piece adapter connected to an end of a 12 cm sample connection tube which at the other end has attached a filter support cap having a 0 47 mm or 25 mm, 2.2 qm pore size, quartz filter (QM-A, Whatman) which was connected to a pump to create an airflow which triggers the flow sensor and the foil substrate is heated.
  • a filter support cap having a 0 47 mm or 25 mm, 2.2 qm pore size, quartz filter (QM-A, Whatman) which was connected to a pump to create an airflow which triggers the flow sensor and the foil substrate is heated.
  • the device was connected, as well, to a controller comprising batteries and the required electronics to heat the drug foil.
  • a testing device were a Heat Source 1 is mechanically and electrically attached.
  • Device 1 has an air inlet and air outlet and a 1 F capacitor (Phoenix Gold Titanium series) capacitor to be discharged to resistively heat the substrate ( ⁇ 0.2 sec) and facilitate rapid aerosol formation with a cross-foil airflow of ⁇ 30 litre per minute.
  • Calibration for temperature versus applied voltage was determined with a thermocouple spot-welded to the foil surface.
  • Device 2 Handheld housing
  • a 100 mm long device such as that in Figure IB, the same shape as that of the Adasuve® device, moulded from PermaStat® resin (antistatic material).
  • Heat Source 1 Testing electric heating
  • Heat Source 2 Chemical heat package
  • a 47.2 x 47.2 x 0.38 mm 304-stainless steel drug foil substrate is attached to a chemical heat package connected to Device 2.
  • One chemical heat package is shown in Figure ID.
  • Heat Source 3 Electric heating
  • apomorphine HC1 (APO) was coated on 2.27 cm 2 (0.44 mg/cm 2 ) on the drug foil substrate of Heat Source 1 or 2 and heated to the temperatures specified in the table below.
  • Apomorphine HC1 was deposited on the drug foil substrate of Heat Source 1 or 2.
  • the content of drug on the drug foil substrate is measured by weight after deposition and the samples grouped based on the calculated area density.
  • Figure 3 A is a plot of the purity of the emitted aerosol versus the area density of the coated apomorphine HC1. The plot shows that the higher the area density, the purer the aerosol generated. This effect can be best seen in the 400°C and 310°C temperature points.
  • Figure 3B is a plot of the % vaporization versus the area density of the coated apomorphine HC1. The plot shows that the higher the are density the lower the emitted dose.
  • Apomorphine HC1 was coated onto Heat Source 3.
  • the drug foil substrates were electrically heated to 316 ⁇ 8 °C and the target temperature was maintained for a Temperature Dwelling Time (TDT).
  • TDT Temperature Dwelling Time
  • Target ED target emitted dose
  • areas and doses coated area density
  • Time To Target Temperature TTT
  • Temperature Dwelling Time TTT
  • Emitted Dose ED

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Abstract

L'invention concerne un dispositif médical portatif approprié pour générer une dose émise d'un aérosol à condensation de médicament par vaporisation thermique d'un film de médicament solide, le dispositif comprenant : une voie aérienne définie par des parois internes ; une entrée d'air au niveau d'une extrémité de la voie aérienne ; une sortie d'air, conçue sous la forme d'un embout buccal, au niveau d'une autre extrémité de la voie aérienne ; un substrat de feuille de médicament ayant une surface imperméable, avec ou sans perforations, placé à l'intérieur de la voie aérienne ; un support de substrat de feuille de médicament ; et un film de médicament solide revêtu sur le substrat de feuille de médicament. Le dispositif médical portatif est conçu pour chauffer le substrat de feuille de médicament entre 260 et 400° C ; la teneur en médicament dans le film de médicament solide est comprise entre 1,5 et 10 fois la dose émise ; et le médicament est de l'apomorphine, ses sels pharmaceutiquement acceptables, ses polymorphes, ses promédicaments et/ou des combinaisons de ceux-ci.
PCT/US2022/052908 2021-12-14 2022-12-14 Dispositifs portatifs et procédés pour produire des aérosols à condensation d'apomorphine de haute pureté WO2023114341A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002094216A2 (fr) * 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Administration de stimulants par voie d'inhalation
US20040099269A1 (en) * 2001-05-24 2004-05-27 Alexza Molecular Delivery Corporation Drug condensation aerosols and kits
US20190117909A1 (en) * 2015-03-11 2019-04-25 Alexza Pharmaceuticals, Inc. Use of antistatic materials in the airway for thermal aerosol condensation process
US20210046259A1 (en) * 2018-02-02 2021-02-18 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002094216A2 (fr) * 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Administration de stimulants par voie d'inhalation
US20040099269A1 (en) * 2001-05-24 2004-05-27 Alexza Molecular Delivery Corporation Drug condensation aerosols and kits
US20190117909A1 (en) * 2015-03-11 2019-04-25 Alexza Pharmaceuticals, Inc. Use of antistatic materials in the airway for thermal aerosol condensation process
US20210046259A1 (en) * 2018-02-02 2021-02-18 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device

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