WO1999056807A1 - Appareil d'inhalation par dose unitaire et procede de distribution a l'aide de ce dernier - Google Patents

Appareil d'inhalation par dose unitaire et procede de distribution a l'aide de ce dernier Download PDF

Info

Publication number
WO1999056807A1
WO1999056807A1 PCT/US1999/009413 US9909413W WO9956807A1 WO 1999056807 A1 WO1999056807 A1 WO 1999056807A1 US 9909413 W US9909413 W US 9909413W WO 9956807 A1 WO9956807 A1 WO 9956807A1
Authority
WO
WIPO (PCT)
Prior art keywords
housing
medicament
volume
inhaler apparatus
holder
Prior art date
Application number
PCT/US1999/009413
Other languages
English (en)
Inventor
Ignatius Loy Britto
Jason Christopher Billig
Fredric Scott Stiber
Original Assignee
Glaxo Group Limited
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 Glaxo Group Limited filed Critical Glaxo Group Limited
Priority to DE69936918T priority Critical patent/DE69936918T2/de
Priority to AU36720/99A priority patent/AU3672099A/en
Priority to JP2000546830A priority patent/JP4242070B2/ja
Priority to EP99918915A priority patent/EP1079881B1/fr
Publication of WO1999056807A1 publication Critical patent/WO1999056807A1/fr

Links

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
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • 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
    • A61M11/001—Particle size control
    • A61M11/003—Particle size control by passing the aerosol trough sieves or filters
    • 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
    • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0043—Non-destructive separation of the package, e.g. peeling
    • 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
    • A61M15/02—Inhalators with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
    • 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
    • A61M2202/06—Solids
    • A61M2202/064—Powder

Definitions

  • the present invention relates generally to inhaler apparatuses, and more particularly, to compact, environmentally friendly, inexpensive dry powder unit dose inhalers.
  • systemic delivery via the lung can increase bioavailability of some medications by avoiding metabolic inactivation of the medicament in the gut or liver.
  • Respiratory delivery to the blood stream also avoids the potential risk of disease transmission from using intravenous delivery devices such as hypodermic needles.
  • MDIs propellant based metered dose inhalers
  • chlorofluorocarbons as propellants are being phased out in favor of more environmentally friendly powder inhalers.
  • Dry powder inhalers which lack any propellants whatsoever, are viewed as one solution to the alleged problem caused by ozone depleting propellants. Dry powder inhalers are of three basic varieties: Reservoir based Dry Powder Inhalers (RDPIs); Multi-unit dose Dry Powder Inhalers (MDPIs); and Unit dose Dry Powder Inhalers (UDPIs).
  • RDPIs meter doses in the device out of a powder reservoir to provide multiple doses of medication, while MDPIs contain multiple premeasured, individually packaged doses of drugs.
  • UDPIs in comparison, contain a single dose of medicament.
  • UDPIs are generally speaking less complex, more compact and less expensive than RDPIs and MDPIs. Moreover, RDPIs and MDPIs are not ideally suited for delivering therapies only needing a single application, especially where disposability after use is a desirable feature.
  • Prior art UDPIs unfortunately, in some instances remain relatively bulky and awkward and may be made from environmentally unfriendly, non- biodegradable materials, such as certain plastics. Examples of prior art UDPIs include that disclosed in U.S. Patent No.
  • PCT Patent Publication No. WO 97/05918 to Asking discloses a UDPI having a dry powder dose sandwiched between two peelable cover strips. The cover strips are pulled from the device, thus internally exposing the drug in a flow path.
  • PCT Publication No. 96/222802 assigned to Directhaler discloses a straw-like UDPI having a dose contained within the straw and which is sealed by removable end caps.
  • the inhaler apparatus comprises a flexible housing having first and second walls.
  • the housing defines an air inlet and an air outlet and an internal housing volume.
  • the housing is preferably deformable or expandable so as to expand the -4-
  • housing volume from a non-inhalation state having a first housing volume, to an inhalation state having a second housing volume.
  • the second housing volume is greater than the first housing volume.
  • An air flow chamber is defined within the housing between the air inlet and the air outlet when the housing is in its inhalation state.
  • a medicament dose which may be a therapeutic or diagnostic agent, is positioned within the housing between the first and second walls.
  • the medicament is sealed from the outside environment in the non-inhalation state. This sealed arrangement prohibits the medicament from falling out of the device, and also prevents air and moisture ingress into the device, thus preserving the sterility and stability of the medicament dose.
  • the housing volume is expanded to its inhalation state, increasing the distance between at least portions of the interior surfaces of the first and second walls.
  • the movement of the walls exposes the medicament contained in the housing within the air flow chamber.
  • a patient inhales through the air outlet and entrains the medicament in an inhalation stream.
  • the medicament flows through the inhalation stream, where it may pass directly to the air outlet and into the patient's lungs.
  • the dosage may first be deagglomerated before passing to the air outlet and into the patient's lungs, for instance, by impacting on various surfaces in the device, or through vibrational effects provided by components within the device.
  • the UDPI of the present application may further include one or more one-way valves to allow airflow from the device to the patient's lungs, but prevent the user from exhaling through the device, so as to blow the drug out of the device.
  • UDPI apparatus and method of use that facilitates patient compliance with prescribed instructions for the medicament within the inhaler by being easy to use.
  • Figure 1 of the drawings is a perspective view of an assembled inhaler apparatus of the present invention in an inhalation state; -6-
  • Figure 2 of the drawings is a perspective view of an assembled inhaler apparatus of the present invention in a non-inhalation state
  • Figure 3 of the drawings is an interior plan view of an unassembled inhaler apparatus of the present invention
  • Figures 3A, 3B and 3C of the drawings are enlarged, isolated cross- sectional views of alternative structures for confining medicament in an inhaler apparatus of the present invention
  • Figure 4 of the drawings is an exterior plan view of an unassembled inhaler apparatus of the present invention
  • Figure 5 of the drawings is a top plan view of an assembled inhaler apparatus of the present invention in a non-inhalation state
  • Figure 6 of the drawings is a top plan view of the inhaler apparatus of the present invention in an inhalation state
  • Figure 7 of the drawings is a cross-sectional side view of the inhaler apparatus of the present invention in an inhalation stf '.e wherein filter flap 56 is shown in one manner of attachment;
  • Figure 8 of the drawings is a cross-sectional side view of the inhaler apparatus of the present invention in an inhalation state wherein filter flap 56 is shown in an alternative manner of attachment;
  • Figures 9A and 9B of the drawings are cross-sectional views of an alternative embodiment of an inhaler apparatus of the present invention;
  • Figure 10 of the drawings is a cross-sectional view of an inhaler apparatus of Figures 9A and 9B with a series of deagglomerators;
  • Figures 1 1A and 1 1 B of the drawings are cross-sectional views of another alternative embodiment of an inhaler apparatus of the present invention.
  • a UDPI apparatus and method of use are disclosed wherein the UDPI can be activated by inhalation by the user.
  • the unit dose inhaler apparatus comprises a paper material, such as a 14-16 point solid bleached sulfate (SBS) laminated with 00035 foil or TYVEK®, manufactured by DuPont, that is capable of being dye cut according to the structures described hereinbelow.
  • SBS solid bleached sulfate
  • the unit dose inhaler apparatus of the instant invention can be discarded after the unit dose is taken by the patient. It is envisioned, however, in accordance with this invention that any other suitable material or materials could be used for construction of the present unit dose inhaler apparatus.
  • inhaler apparatus 10 comprises a flexible housing, generally referred to as 12.
  • Housing 12 includes an integral first wall 14 and an integral second wall 16 and possesses an internal housing volume 13 (not shown in Figures 1-4).
  • the walls of other embodiments of the inhaler apparatus of this invention can be separate but abutting with various configurations of the housing.
  • housing 12 further comprises an air inlet port 18, which, preferably takes the form of a pair of spaced-apart but proximate air inlet ports on first wall 14 of housing 12.
  • Housing 12 also comprises a mouthpiece or air outlet port 20 defined by portions of both first wall 14 and second wall 16 and substantially on the opposite side of housing 12 from air inlet port 18.
  • first wall 14 of housing 12 further comprises a series of flaps and folds by which first wall 14 is connected to second wall 16 and by which expandability is imparted to the internal housing volume 13 of housing 12.
  • First wall 14 comprises a pair of outer side flaps 22 extending laterally therefrom with side flaps 22 being foldably attached along lower folds 24 to side walls 26, which are formed between lower folds 24 and medial side wall folds 28.
  • Upper side walls 30 are formed between medial side wall folds 28 and upper folds 32.
  • Distal tabs 34 are formed along a distal edge of first wall 14 and are foldable along fold 36. Between distal tabs 34 is formed an arcuate segment 38.
  • Primary fold 40 is defined along proximal edges of walls 14 and 16 and forms a connection between walls 14 and 16 of housing 12. Lateral arcuate edges 42 extend away from primary fold 40 in an arcuate path along the periphery of second wall 16.
  • Projections 44 are defined between arcuate lateral edges 42 of second wall 16 and arcuate segment 46.
  • arcuate segment 46 is defined along the distal edge of second wall 16 of housing 12 and lies between projections 44.
  • instructional indicia 64 can be placed on first wall 14.
  • Second wall 16 of housing 12 has an interior surface 48.
  • First wall 14 of housing 12 defines an interior surface 52.
  • valve flap or filter flap 56 is attached on interior surface 52 of first wall 14, such that filter flap 56 covers air inlet port 18.
  • second wall 16 of housing 12 further comprises interior surface 48.
  • First wall 14 of housing 12 further comprises interior surface 52.
  • Interior surfaces 48 and 52 are designed to contain, in various ways, a medicament dose 62.
  • medicament dose 62 can be positioned between interior surfaces 48 and 52 without the use of a separate cover layer (the signi f icance of which is described below with reference to the second and third embodiments) when, during assembly, first wall 14 is folded over second wall 16 (along primary fold 40), such that internal surfaces 48 and 52 face each other.
  • Interior surfaces, 52 and 48, respectively, can, by virtue of an adhesive A encircling dose 62, form a dose or medicament holder 58 (Figure 5), which defines an internal holder volume 60 for containing dose 62.
  • medicament holder 58 is formed by a single holder cover portion 54 which is adhesively bonded by adhesive A to interior surface 48, with dose 62 sandwiched therebetween.
  • medicament holder 58 is formed between a first holder cover portion 50 and a second holder cover portion 54 which are bonded together by adhesive A with dose 62 sandwiched therebetween.
  • the first of the three embodiments described above may be assembled by first metering a quantity of a medicament into interior surface 52 of first wall 14. A pressure-sensitive and biologically safe adhesive A is then spread around medicament 62.
  • the adhesive is preferably a natural rubber base, pressure-sensitive adhesive preferably having the property of not sticking to anything but its own substrate and to itself after it dries. Booth, K.N. ed. Industrial Packing Adhesives, Blackey: Glasgow, 1990.
  • Outer side flaps 22 of first wall 14 are then folded along medial side wall folds 28, and tabs 34 are folded along folds 36.
  • the preferred natural rubber adhesive is then placed along the surfaces of side flaps 22 and tabs 34 that face second wall 16.
  • Second wall 16 is then folded along primary fold 40 and moved into contact with side flaps 22 and tabs 34. Second wall 16 is moved in such a manner so as to ensure that arcuate segments 38 and 46 are adequately aligned to form air inlet port 20. Suitable pressure is then applied to second wall 16 so that the pressure-sensitive adhesive A on the abutting surfaces of side edges 22, tabs 34, and around medicament 62 adequately adheres between first and second walls 14, 16. So arranged, adhesive A surrounding medicament 62 confines the medicament 62 to the -10-
  • single medicament cover portion 50 can be used within inhaler 10.
  • Cover portion 50 may be made of any suitable material, a metal or plastic foil being most preferred.
  • the single medicament holder cover portion 50 can be mounted with adhesive A on interior surface 52 generally in a medial position. As would be understood, mounting could also be made on the interior surface 48 of second wall 16 without departing from the scope of the present invention.
  • Medicament dose 62 is then loaded onto cover portion 50 and a suitable adhesive is then spread around medicament 62 about the periphery of cover portion 54.
  • the device is assembled as described above in the discussion of the first embodiment, thus forming an adhesive bond between interior surface 48 of second wall 16 and the peripheral edge of cover portion 50. So constructed, medicament holder 58 is formed between cover portion 50 and interior surface 48.
  • medicament holder 58 is formed from a pair of cover portions 50 and 54 which when sealed together to form an envelope for containing medicament 62.
  • the envelope for medicament holder 58 may be formed by positioning first holder cover portion 50 on interior surface 52 of first wall 14, and second holder cover portion 54 on interior surface 48 of second wall 16. A suitable adhesive is then applied to the periphery of one of the cover portions, and the inhaler is assembled, as described above.
  • medicament holder 58 may also be made as a discrete unit, separately from the rest of the inhaler apparatus.
  • medicament holder 58 is fabricated by metering the selected medicament onto a first cover portion. A second cover portion is placed over the deposited medicament and the cover portions are sealed together using heat, adhesive or any other suitable means known to those skilled in the art to form holder 58. The assembled medicament holder 58 may then be adhered with inhaler 10 on either interior surface 52 or 48, and assembly completed as described herein.
  • medicament holder 58 can be defined by the internal volume of housing 12.
  • cover slips are used to seal air inlet port and air outlet port 18 and 20, respectively, thus sealing medicament 62 within housing 12.
  • Suitable techniques include measuring volumes or weights of medicament directly onto surface 48, or cover portion 54, such as by vacuum tube; evaporation from suspension or solution, or by electrostatic deposition.
  • medicaments may also be placed on or into a suitable carrier such as beads, meshes, fibrous materials of films, as discussed for example in U.S. Patent Nos. 5,619,984 and 5,647,347, both of which are hereby incorporated by reference.
  • a suitable carrier such as beads, meshes, fibrous materials of films, as discussed for example in U.S. Patent Nos. 5,619,984 and 5,647,347, both of which are hereby incorporated by reference.
  • These alternate substrates may be positioned in the internal housing volume as would be recognized by those of ordinary skill, to achieve substantially the same function and result in substantially the same was described above.
  • Medicament 62 may comprise any diagnostic or therapeutic agent that is suitable for inhalation.
  • particles suitable for respiration have an aerodynamic diameter of between 0.5 and 10 micrometers.
  • Appropriate medicaments may thus be selected from , for example, -12-
  • analgesics e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, e.g., diltiazem; antiallergics, e.g., cromoglycate, ketoifen or nedocromil; antiinfectives, e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine; antihistamines, e.g., methapyriiene; anti-inflammatories, e.g., beclomethasone dipropionate, fluticasone propionate, flunisolilde, budesonide, rofleponide, mometasone furcate or triamcinolone acetonide; antitussives, e.g., noscapine; bronchodilators, e.g., albuterol, sal
  • the medicaments may be used in the form of salts, (e.g.. as alkali metal or mine salts or as acid addition salts) or as esters (e.g., 'ower alkyl esters) or as solvates (e.g., hydrates) to optimize the activity and/or stability of the medicament.
  • salts e.g.. as alkali metal or mine salts or as acid addition salts
  • esters e.g., 'ower alkyl esters
  • solvates e.g., hydrates
  • Preferred medicaments are selected from albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate and salts or solvates thereof, e.g., the sulphate of albuterol and the xinafoate of salmeterol.
  • Medicaments can also be delivered in combinations.
  • Preferred formulations containing combinations of active ingredients contain salbutamol (e.g., as the free base or the sulphate salt) or salmeterol (e.g., -13-
  • an anti-inflammatory steroid such as a beclomethasone ester (e.g., the dipropionate) or a fluticasone ester (e.g., the propionate).
  • Combinations of medicaments may be premixed compounds delivered in a single medicament holder.
  • combinations may be single compounds individually packaged in separated medicament holders, with combinations of such different medicaments being presented in the same device.
  • any suitable therapeutic or diagnostic agent can be included as medicament 62 within medicament holder 58 or the present UDPI apparatus.
  • the medicament may be a pure drug, or drug mixed with an excipient, for example, lactose.
  • FIG. 5 a ready-to-use inhaler apparatus 10 is presented wherein the internal housing volume 13 of housing 12 can be minimal, even zero, in a non-inhalation state.
  • Medicament holder 58 having an internal volume 60, and including medicament 62 within its internal volume 60, is presented in phantom as it is contained within the interior of apparatus 10.
  • Apparatus 10 can further comprise instructional indicia 64 which advise the user as to the direction in which the user must push medial side wall folds 28 to place inhaler apparatus 10 in its operable position.
  • An air flow chamber 68 is simultaneously formed within housing 12 between air inlet ports 18 and air outlet port 20. Air flow can be created between air inlet ports 18 and air outlet port 20 by inhalation by the user as illustrated by air flow arrows 70.
  • Expansion of housing 12 to an inhalation state preferably pulls medicament holder cover portion 54, which is mounted on the interior surface 52 of first wall 14, away from medicament holder portion 50, which is mounted on the interior surface 48 of second wall 16.
  • the expansion of housing 12 to the inhalation state pushes walls 14 and 16 away from each other to break the seal between medicament holder portion 50 and medicament holder cover portion 54, thereby opening medicament holder 58.
  • Medicament 62 contained within internal holder volume 60 of medicament holder 58 is thus exposed to air flow chamber 68 and the air flow along arrows 70 once the user inhales through air outlet port 20 to create the air flow represented by arrows 70.
  • Medicament 62 then flows along air flow depicted by arrows 70 into the mouth and ultimately into the lungs of the user, where medicament 62 is delivered to the desired location within the lung.
  • medicament 62 is exposed to air flow within air chamber 68 simultaneously with the expansion of housing volume 13 of housing 12.
  • this expansion pulls medicament holder cover portion 54, which is mounted on the interior surface 52 of first wall 14, away from opposing second wall 16 or, if two cover portions are included in inhaler apparatus 10, away from medicament holder portion 50 which is mounted on the interior surface 48 of second wall 16.
  • the expansion of housing 12 to the inhalation state breaks the adhesive seal holding medicament holder 58 together and releases the contents thereof within the air flow chamber 68.
  • the seal between cover portion 54 and either second wall 16 or cover portion 50 must be such that the layers can be peeled apart to expose the drug in the device.
  • exposure of the medicament may be provided by using tearable cover portion materials. In such an instance, the shear force exerted on the cover portion(s) as it (they) are pulled by the housing walls during the transition to the inhalation state ruptures at least one of the cover portions to expose the contents thereof, as described below.
  • valve or filter flap 56 comprises a non-porous material, such as foil or plastic film, and is attached to first wall 14 on the opposite side of air inlet port 18 from primary fold 40.
  • flap 56 includes an attached end 72 and a free end 74. At rest, free end 74 rests against first wall 14 and prevents entry of undesirable contaminants into the interior of inhaler apparatus 10. During use, however, free end 74 of filter flap 56 proceeds toward air outlet port 20 as air flow proceeds along arrows 70 through air flow chamber 68. As free end 74 moves in this manner, filter flap 56 extends substantially vertically into the interior of inhaler apparatus 10, which prevents some portion of medicament 62 from spilling from inhaler apparatus 10 via air inlet ports 18 or from being blown from the device should the user erroneously exhale through the device. This feature facilitates the consumption of the predetermined unit dose of medicament 62 provided in inhaler apparatus 10.
  • filter flap 56 comprises a porous filter material.
  • filter flap 56 is attached to first wall 14, around its periphery, including its ends 72, 74.
  • the pores of filter flap 56 are of a sufficiently small diameter to preclude entry into the interior of apparatus 10 of unwanted particulate contaminants, while at the same time allowing for air to flow through apparatus 10 along the path described by arrows 70. Additionally, the pores of filter flap 56 may be of a sufficiently small diameter to preclude the loss of medicament 62 through air inlet port 18.
  • filter flap 56 facilitates the administration of an appropriate unit dose to the patient using inhaler apparatus 10 in that substantially all of medicament 62 passes out of inhaler apparatus 10 through air outlet port 20 along the air path described by arrows 70 and into the patient's lungs.
  • filter flap 56 may serve several functions. Flap 56 can permit the passage of air through air inlet ports 18 so that medicament within inhaler apparatus 10 can be inhaled. When a porous material is used, flap 56 prevents the entry of undesirable particles into the interior of housing 12. When a non-porous -17-
  • flap 56 prevents a person using inhaler apparatus 10 from exhaling through the air outlet and blowing the dose out of the air flow chamber through the air inlet ports prior to inhaling the dose into his or her lungs.
  • flap 56 prevents a person using inhaler apparatus 10 from exhaling through the air outlet and blowing the dose out of the air flow chamber through the air inlet ports prior to inhaling the dose into his or her lungs.
  • flap 56 prevents a person using inhaler apparatus 10 from exhaling through the air outlet and blowing the dose out of the air flow chamber through the air inlet ports prior to inhaling the dose into his or her lungs.
  • flap 56 prevents a person using inhaler apparatus 10 from exhaling through the air outlet and blowing the dose out of the air flow chamber through the air inlet ports prior to inhaling the dose into his or her lungs.
  • flap 56 prevents a person using inhaler apparatus 10 from exhaling through the air outlet and blowing the dose out of the air flow chamber through the air inlet ports
  • inhaler apparatus 10 can optionally include additional features to suitably deagglomerate the micronized or particulate drug when the inhaler is used in the manner described above.
  • the deagglomerating mechanisms include any known to those of ordinary skill, and include, without limitation the following: inhaler apparatus 10 may be fitted with deagglomerator D, shown in one embodiment as a mesh screen, which is positioned between medicament 62 and mouthpiece 20 upon which medicament 62 impacts upon inhalation to break up agglomerated drug particles and increasing fine particle mass.
  • inhaler apparatus 10 may include angled abutment surfaces for creating a tortuous walled pathway through which medicament 62 passes and impacts against during inhalation to achieve the same results.
  • the selected cover portion 50 or 54 on which the drug is positioned may be made of a suitable material and affixed to the selected interior surface of housing 12 in such a manner that the selected cover portion vibrates upon inhalation, again assisting in deagglomeration. -18-
  • inhaler apparatus 100 has a housing 102, which can be tubular, having a proximal end 104, a distal end 106 and a central bore 108 extending therebetween.
  • a housing 102 which can be tubular, having a proximal end 104, a distal end 106 and a central bore 108 extending therebetween.
  • an air inlet 110 is defined in housing 102 within the region of distal end 106 and air outlet 112 is defined within the region of proximal end 104.
  • a first wall 120 and a second wall 130 are positioned within central bore 108 and are movable along the internal length of central bore 108.
  • Medicament M can be maintained on or packed in beads between deagglomeration screens 140 and 142.
  • walls 120 and 130 are located between the air ports 110 and 112.
  • a seal can be present between the inner length of housing 102 and peripheral edges of walls 120 and 130 to prevent medicament M from movement.
  • the internal volume of housing 102 between walls 120 and 130 is minimal and no air flow chamber is yet formed between air inlet 110 and air outlet 112.
  • walls 120 and 130 are drawn to their inhalation state by pulling them away from each other and toward opposite ends of housing 102 as shown in Figure 9B.
  • String S can be used to accomplish such movement of walls 120 and 130 by a user pulling the strings.
  • the internal housing volume is increased and, as walls 120 and 130 are drawn past air outlet 112 and air inlet 110, respectively, an air flow chamber is formed within central bore 108 between air inlet 110 and air outlet 112.
  • Suitable means, such as inwardly directed lips 122 may be suitably placed at central bore 108 to prevent walls 120 and 130 from being withdrawn from the bore completely.
  • the user For use in the inhalation state, the user inhales through air outlet 112 to cause an air flow within central bore 108. Particles of medicament M are entrained in the air flow and the drug can be carried to the lungs of the user.
  • inhaler apparatus 150 is illustrated and is very similar to inhaler apparatus 100 of Figures 9A and 9B.
  • Inhaler apparatus 150 differs by including a series of additional, spaced-apart deagglomerators D1 , D2 and D3, which are illustrated in a preferred embodiment as screens.
  • Deagglomerators D1 , D2 and D3 are attached to string S which, in this embodiment, extend.-- through one end of housing 102 and to deagglomerator screen 140.
  • deagglomerators D1 , D2 and D3 Upon moving the device from the non-inhalation state to the inhalation state, deagglomerators D1 , D2 and D3 are moved from a stacked arrangement against screen 140 and the positions depicted in Figure 10, to aide in further breaking up agglomerated powder particles.
  • inhalation apparatus 200 comprises a housing 202 having an expandable and collapsible accordion-like length.
  • a first wall 210 is at one end of the housing, and a second wall 220 is at the opposite end.
  • An air inlet port 230 and an air outlet port 240 are formed in opposite ends of housing 202, in walls 210 and 220 or in the length of the housing.
  • a medicament dose M is positioned medially in the length of the housing between the ends, as medicament M is attached to a substrate X which in Figures 11A and 11 B takes the form of a mesh.
  • this accodian embodiment is collapsed, compressed into a compact, low profile package.
  • the internal volume is minimal, as walls 210 and 220 are in close proximity to each other, and medicament M is positioned therebetween.
  • inlet port 230 and air outlet port 240 are suitably covered to prevent an air flow chamber from being formed therebetween.
  • air inlet and outlet ports 230 and 240 are unsealed, and walls 210 and 220 are drawn away from each other by pulling tabs T thus expanding housing 202.
  • the internal housing volume is increased and an airflow chamber is created within housing 202.
  • the user then may inhale through air outlet port 240, entrain medicament M in the inhalation stream and deliver medicament M to his or her lungs.
  • medicament M may be suitably packaged in these additional embodiments in the same fashion described for all other embodiments: a medicament holder may be formed between the first and second walls themselves, may comprise a single cover portion layer and one wall, or may comprise two cover portions sealed to form an envelope.
  • the medicament may also be carried by substrates.
  • substrates include mesh substrates loaded with drug and fixed within the housing between the walls; or beads loaded with drug and positioned between containment screens within the device.
  • Unidirectional flow valves and deagglomerators can also be incorporated within such alternative devices as described above.
  • Deagglomerators can be fitted into the alternative housings which would act to break up larger particulate agglomerates.
  • one or more screens may be placed within the bore of the tubular embodiment or the baffles embodiment, also between the movable walls. The screens may be linked to each other at slight distances by one or more strings or leaders to form a tow line, such as that depicted in Figure 10. One end of the tow line is anchored at a location within the housing, and the other to the wall toward -21-
  • the proximal end of the device When the proximal-most wall is drawn toward its inhalation state, the screen(s) also move proximally.
  • the leader(s) making up the tow line distances the screens at intervals along the air chamber path as the device is configured to its inhalation state.
  • an inhaler apparatus of this invention is small and compact and is therefore easily carried upon the person of a user.
  • an inhaler apparatus of this invention is also inexpensive to manufacture and can be discarded after its unit dose is consumed.
  • An inhaler apparatus of this invention is also easy to use, thus addressing the problem of patient compliance with prescribed instructions associated with delivery of the medicament. Patient compliance is also facilitated in that inhaler apparatus 10 is easily carried on the patient's person.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Un appareil (10) d'inhalation comprend une enveloppe (12) qui présente des première (14) et deuxième (16) parois et qui définit une entrée (18) et une sortie (20) pour l'air. Les première et deuxième parois définissent un volume intérieur (13) d'enveloppe et comportent des parties qui sont mobiles l'une par rapport à l'autre de manière à dilater le volume intérieur de l'enveloppe entre un état non adapté à l'inhalation, dans lequel le volume intérieur de l'enveloppe occupe un premier volume, et un état adapté à l'inhalation, dans lequel le volume intérieur de l'enveloppe occupe un deuxième volume. Le deuxième volume est plus important que le premier volume. Une chambre (68) à circulation d'air est définie à l'intérieur de l'enveloppe entre l'entrée et la sortie pour l'air lorsque l'enveloppe se trouve dans l'état adapté à l'inhalation. Un médicament (62) est contenu entre les première et deuxième parois. Le médicament est exposé à l'intérieur de la chambre à circulation d'air lorsque l'enveloppe se trouve dans l'état adapté à l'inhalation.
PCT/US1999/009413 1998-05-04 1999-04-29 Appareil d'inhalation par dose unitaire et procede de distribution a l'aide de ce dernier WO1999056807A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE69936918T DE69936918T2 (de) 1998-05-04 1999-04-29 Inhaliergerät für Einzeldosen
AU36720/99A AU3672099A (en) 1998-05-04 1999-04-29 Unit dose inhaler apparatus and method of delivery using same
JP2000546830A JP4242070B2 (ja) 1998-05-04 1999-04-29 単位用量吸入装置およびこれを用いた放出法
EP99918915A EP1079881B1 (fr) 1998-05-04 1999-04-29 Appareil d'inhalation par dose unitaire

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US8403898P 1998-05-04 1998-05-04
US60/084,038 1998-05-04
GB9810126.4 1998-05-13

Publications (1)

Publication Number Publication Date
WO1999056807A1 true WO1999056807A1 (fr) 1999-11-11

Family

ID=22182490

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/009413 WO1999056807A1 (fr) 1998-05-04 1999-04-29 Appareil d'inhalation par dose unitaire et procede de distribution a l'aide de ce dernier

Country Status (1)

Country Link
WO (1) WO1999056807A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6443152B1 (en) 2001-01-12 2002-09-03 Becton Dickinson And Company Medicament respiratory delivery device
WO2002081016A1 (fr) * 2001-04-05 2002-10-17 Microdrug Ag Procede et dispositif permettant de liberer de la poudre
US6644309B2 (en) 2001-01-12 2003-11-11 Becton, Dickinson And Company Medicament respiratory delivery device and method
US6722364B2 (en) 2001-01-12 2004-04-20 Becton, Dickinson And Company Medicament inhalation delivery devices and methods for using the same
EP3283151B1 (fr) * 2015-04-15 2022-07-20 Philip Morris Products S.A. Inhalateur de poudre sèche et procédé d'utilisation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3949751A (en) * 1970-03-03 1976-04-13 Fisons Limited Method and device for dispensing medicament to the body
US4508116A (en) * 1982-12-28 1985-04-02 Products For Health And Industry Carbon dioxide rebreathing apparatus
US5582162A (en) * 1992-11-27 1996-12-10 Astra Aktiebolag Inhaler for multiple use

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3949751A (en) * 1970-03-03 1976-04-13 Fisons Limited Method and device for dispensing medicament to the body
US4508116A (en) * 1982-12-28 1985-04-02 Products For Health And Industry Carbon dioxide rebreathing apparatus
US5582162A (en) * 1992-11-27 1996-12-10 Astra Aktiebolag Inhaler for multiple use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1079881A4 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6443152B1 (en) 2001-01-12 2002-09-03 Becton Dickinson And Company Medicament respiratory delivery device
US6644309B2 (en) 2001-01-12 2003-11-11 Becton, Dickinson And Company Medicament respiratory delivery device and method
US6722364B2 (en) 2001-01-12 2004-04-20 Becton, Dickinson And Company Medicament inhalation delivery devices and methods for using the same
US6929005B2 (en) 2001-01-12 2005-08-16 Becton, Dickinson And Company Medicament respiratory delivery device, cartridge and method of making same
US7270127B2 (en) 2001-01-12 2007-09-18 Becton, Dickinson And Company Medicament respiratory delivery device
WO2002081016A1 (fr) * 2001-04-05 2002-10-17 Microdrug Ag Procede et dispositif permettant de liberer de la poudre
EP3283151B1 (fr) * 2015-04-15 2022-07-20 Philip Morris Products S.A. Inhalateur de poudre sèche et procédé d'utilisation

Similar Documents

Publication Publication Date Title
US6098619A (en) Unit dose inhaler apparatus and method of delivery using same
CA2444129C (fr) Methode et dispositif d'inhalation
US6941947B2 (en) Unit dose dry powder inhaler
EP1173368B1 (fr) Support pour medicaments
US6915802B1 (en) Medicament pack
US20080190424A1 (en) Unit dose dry powder inhaler
US9050427B2 (en) Dry powder inhalers with multi-facet surface deagglomeration chambers and related devices and methods
EP3086829B1 (fr) Inhalateur de poudre sèche
US20090250058A1 (en) Inhalation System and Delivery Device for the Administration of a Drug in the Form of Dry Powder
IL108780A (en) inhaler
WO2006031712A2 (fr) Systemes de confinement de medicament en poudre seche tubulaire, inhalateurs et procedes associes
WO2005030305A1 (fr) Ensemble d'ouverture de recipients pour medicaments, en particulier des recipients pour medicaments en poudre
US20130025593A1 (en) Dry powder inhaler
US20060076010A1 (en) Drug delivery system with vented mouthpiece
WO1999056807A1 (fr) Appareil d'inhalation par dose unitaire et procede de distribution a l'aide de ce dernier
WO2008139490A2 (fr) Inhalateur de poudre sèche à multiples doses
WO2002030501A1 (fr) Production d"un aérosol au moyen d"une membrane frangible
WO2024100652A1 (fr) Inhalateur de poudre sèche haute performance

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1999918915

Country of ref document: EP

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 546830

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 1999918915

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWG Wipo information: grant in national office

Ref document number: 1999918915

Country of ref document: EP