EP2254630A1 - Inhalateurs de poudre - Google Patents

Inhalateurs de poudre

Info

Publication number
EP2254630A1
EP2254630A1 EP08716990A EP08716990A EP2254630A1 EP 2254630 A1 EP2254630 A1 EP 2254630A1 EP 08716990 A EP08716990 A EP 08716990A EP 08716990 A EP08716990 A EP 08716990A EP 2254630 A1 EP2254630 A1 EP 2254630A1
Authority
EP
European Patent Office
Prior art keywords
powder inhaler
amino
phenyl
quinazoline
chloro
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.)
Withdrawn
Application number
EP08716990A
Other languages
German (de)
English (en)
Inventor
Marc Egen
Michael Krueger
Joerg Schiewe
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.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
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 Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Publication of EP2254630A1 publication Critical patent/EP2254630A1/fr
Withdrawn legal-status Critical Current

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
    • A61M15/00—Inhalators
    • A61M15/0001—Details of inhalators; Constructional features thereof
    • A61M15/0021—Mouthpieces therefor
    • A61M15/0025—Mouthpieces therefor with caps
    • A61M15/0026—Hinged caps
    • 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
    • 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
    • A61M15/0065—Inhalators with dosage or measuring devices
    • 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 invention relates to a powder inhaler for the administration of moisture-sensitive pharmaceutical formulations.
  • the medical pulmonary inhalation aerosol therapy by nebuliser, metered dose inhaler or dry powder inhaler plays an important role in the treatment of numerous diseases and in particular respiratory diseases.
  • single-dose and multi-dose devices are known. These may be in the form of disposable or reusable devices.
  • dosage may be in the form of capsules containing a powder formulation. Is a capsule as
  • Blister pack which has a plurality of circularly arranged cavities include.
  • the individual cavities each contain a dose of a medicament powder intended for inhalation.
  • the cavities are closed on both sides, eg by a sealing foil.
  • To dispense the drug powder the cavity is opened.
  • One Air duct connects the open cavity with the mouthpiece of the inhaler.
  • the inhaler of DE 3336486 is described in more detail. This has a housing in which a chamber (storage chamber) is found, which has an air inlet and in which there is a disc-shaped, round blister with packaged medicine bags. The blister is loosely connected to a round, rotatable disc.
  • the chamber has an air outlet.
  • the inhaler also has a piston which is arranged so that it can open a drug pocket piercing each, so that the drug is released into the chamber and can be inhaled via a mouthpiece.
  • DE 4106379 describes an inhalation device into which a blister or the like for a powdered medicament can be introduced.
  • the blister consists of two mutually peelable webs of material, which define at least one container in which the drug is located.
  • the device is provided with a device which extracts the two webs of material at an opening station to open a container. Through an outlet part, such as a mouthpiece, which is connected to the opened container, the user can inhale the powdered medicine from the opened container.
  • one of the material webs may also be a carrier web with a plurality of pockets and the other material web a cover web. Each pocket and the adjacent area of the cover sheet then form a container.
  • a drive device may be provided which subtracts the carrier web and the cover web from each other.
  • This drive device consists for example of two drive wheels (eg gears), which hold the cover web in drive engagement between them.
  • each individual blister defines a type of storage chamber in the inhaler, which is connected to the mouthpiece via an air channel.
  • the way in which the powder formulation is packaged in the device is decisive for the product quality and thus the suitability for inhalation application.
  • the primary packaging is characterized in that it is in direct contact with the inhalation formulation.
  • the primary packaging may be surrounded by a second outer protection, the secondary packaging.
  • the primary packaging means may e.g. a capsule, a solid or flexible blister with cavities or a disc with cavities.
  • the secondary packaging may be a blister, a bag, a bag or other container.
  • the secondary packaging generally encloses the primary packaging completely. Secondary packaging is used particularly when the primary packaging does not provide adequate protection against moisture.
  • the secondary packaging such as a single or Mehrdosispulverinhalator are made of commercially available plastics.
  • the primary packaging material and optionally the secondary packaging agent have the task of protecting the active ingredient as well as the entire inhalation formulation from chemical or physical changes.
  • physical changes include changes in the cohesion of the active substance particles, changes in the adhesion of
  • Fine particle dose is understood to mean the dose of the pharmaceutical formulation which reaches the lungs of the patient. The latter is influenced by the interactions of the micronized drug particles with each other as well as the interactions with the excipients or with the container walls. It has - A -
  • one of the main purposes of the package is to keep the chemical composition of the atmosphere inside the package constant in order to prevent physical or chemical changes in the drug formulation or to keep the inhalation formulation stable.
  • in use stability and long-term stability, the former being a short-term stability that the inhalation formulation must possess per se, even if not adequately protected by the packaging Stability defined, which must be ensured as long as the inhalation formulation is in the unopened packaging.
  • the material must be such that the secondary pack can be given the necessary shape and the secondary pack can fulfill its intended function.
  • the invention has for its object to provide a powder inhaler with improved properties during long-term storage and during in-use storage of moisture-sensitive drug formulations.
  • the powder inhaler according to the invention is characterized in that a dehydrating material is incorporated into at least one part of the powder inhaler.
  • the invention also relates to the use of the powder inhaler according to the invention for the administration of moisture-sensitive, inhalable medicament formulations.
  • Powder inhalers are - as described above - known from the prior art.
  • the powder inhaler according to the invention is a moisture-sensitive
  • Inhalation formulation which must be stored for a long time in a powder inhaler before it is applied, better shielded from the ingress of moisture from the outside environment than is the case with the comparable powder inhalers known from the prior art.
  • the powder inhaler according to the invention consists of at least one or more parts of dewatering material.
  • Parts of the powder inhaler may e.g. the outer wall, the capsule holder, the capsule chamber or the blister disc be.
  • the dewatering material is incorporated into a wall of the housing of the powder inhaler, more preferably into the capsule chamber (such as the HandiHaler brand device) or into the wall of the reservoir of a reservoir device.
  • the present invention preferably relates to an ensemble of an inhaler for the inhalation of powdered medicaments with a dehydrating material, wherein the inhaler is characterized by a) an upwardly open, cup-shaped lower part (1), which in the casing has two opposite windows (2) and at the edge of the opening has a first hinge element with a hinge pin (3), b) a plate (9) which covers the opening of the lower part (1) covered and having a second hinge element, and a Siebhalterung (11) with a sieve (10) carries, c) a retractable
  • Capsule holder (4) for receiving the capsule which is formed perpendicular to the plane of the plate on the lower-facing side of the plate (9) and on which a head movable against a spring is provided, the head having one or two ground needles (6).
  • a grip aid (17) and a third hinge element and e) a cover (13) having a fourth hinge element, wherein the hinge elements one of the lower part, two of the plate, three of the upper part and four of the lid are interconnected.
  • the inhaler has an actuator (7), which serves to open the lid (13) by the closure element (14) on the lid (13) on the inclined side wall (15) (gglfs. With a reef ment (16)) of the Recess (8) pushes, which acts as Gleitfiumblee on further advancement of the actuator (7) and ensures a release of the lid (13).
  • the guidance of the needle or the needles is realized essentially via two laterally arranged guide arms (18).
  • the guide arms also have the task of keeping the actuator (7) under a bias.
  • the guide arms (18) are provided at their main body remote end with end stops which rest in the rest position of the actuator (7) on the guide sleeves of the capsule holder (4).
  • the guide sleeves are located on the outside of the capsule holder (4).
  • a coil spring (5) is arranged, which extends in its axial extent parallel to the needles or (6), wherein the coil spring (5) is so matched to the length of the guide arms (18) the actuating member (7) is biased in the rest position.
  • Such an inhaler is shown in FIG.
  • the present invention also preferably relates to a multi-dose active powder inhaler as disclosed in PCT / EP2007 / 004417 with a dewatering material.
  • the cover of the mouthpiece is so coupled with a conveyor, such as a pump, and / or with an energy storage, such as a spring accumulator that actuated by opening and / or closing the cover, the conveyor and / or generates energy and in Energy storage is stored.
  • a delivery medium preferably air
  • tensioning the spring accumulator by opening and / or
  • Closing the cover generates stored energy.
  • This allows a very simple, in particular intuitive operation of the inhaler.
  • this allows a particularly simple and therefore cost-effective design.
  • the inhaler may further comprise a gear to provide from the opening and / or closing movement of the cover a preferably axial movement for opening the next receptacle, for moving and / or advancing the memory around a receptacle, for tensioning a spring accumulator, for actuating a conveying device in particular to draw in air, and / or to actuate a counter or other means of the inhaler.
  • the conveying device, the energy store and / or a connection device can be arranged within an annular memory or an annular arrangement of receptacles, each containing a dose of the formulation.
  • the present invention also preferably relates to a passive multidose powder inhaler as disclosed in PCT / EP2007 / 004416 with a dewatering material.
  • the carrier extends over a circumferential angle of the Inhalator of less than 360 °, is guided between two deflections each with at least substantially constant curvature, extends exclusively in a ring segment of the inhaler and / or extends with a connecting two deflections sections exclusively along a peripheral or outer wall of the inhaler.
  • the carrier is band-shaped and / or formed as a blister strip.
  • the recordings are preferably formed by blister pockets.
  • the inhaler also includes a multi-wheel conveyor for incrementally advancing and / or diverting the carrier.
  • the wheels have the same diameter, are arranged on a common radius, by a common drive means, in particular a sun gear o. The like. Drivable and / or have the same direction of rotation.
  • the dewatering material can be incorporated into the blister disk.
  • capsules as primary packaging and blisters filled with an inhalation formulation for use in powder inhalers DE 10 2005 022 862.3 discloses capsules as primary packaging which contain an adsorbent in their walls.
  • EP 04 025 038.3 discloses blisters for use in inhalers which have a dehydrating agent in their walls.
  • Inhalation formulation are here preferably pharmaceutical powder formulations containing as active ingredient an anticholinergic and whose particles have a size of less than 100 micrometers.
  • W is a pharmacologically active agent and (for example) selected from the group consisting of betamimetics, anticholinergics, corticosteroids, PDE4 inhibitors, LTD4 antagonists, EGFR inhibitors, dopamine agonists, HIV antihistamines, PAF- Antagonists and PI3 kinase inhibitors.
  • W represents a betamimetic combined with an anticholinergic
  • W represents an anticholinergic, combined with a betamimetic
  • Corticosteroid, PDE4 inhibitor, EGFR inhibitor or LTD4 antagonist, - W represents a corticosteroid combined with a PDE4 inhibitor, EGFR inhibitor or LTD4 antagonist
  • W represents a PDE4 inhibitor combined with an EGFR inhibitor or LTD4
  • W represents an EGFR inhibitor combined with a LTD4 antagonist.
  • Preferred betamimetics for this purpose are compounds selected from the group consisting of albuterol, arformoterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, isoetharines, isoprenaline, levosalbutamol, mabuterol, meluadrine, metaproterenol , Orciprenaline, Pirbuterol, Procaterol, Reproterol, Rimiterol, Ritodrine, Salmefamol, Salmeterol, Soterenol, Sulphone terol, Terbutaline, Tiaramide, Tolubuterol, Zinterol, CHF-1035, HOKU-81, KUL-1248 and
  • the acid addition salts of the betamimetics are preferably selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate,
  • Hydrophosphate hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.
  • Preferred anticholinergic compounds are compounds which are selected from the group consisting of tiotropium salts, preferably the bromide salt, oxitropium salts, preferably the bromide salt, flutropium salts, preferably the bromide salt, ipratropium salts, preferably the bromide salt, glycopyrronium salts, preferably the bromide salt, trospium salts the chloride salt, tolterodine.
  • the cations are the pharmacologically active ingredients.
  • the abovementioned salts may preferably contain chloride, Bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate or p-toluenesulfonate, with chloride, bromide, iodide, sulfate, methanesulfonate or p-toluenesulfonate being preferred as counterions .
  • the chlorides, bromides, iodides and methanesulfonates are particularly preferred.
  • anticholinergics are selected from the salts of the formula AC-I
  • X ⁇ is a single negatively charged anion, preferably an anion selected from the group consisting of fluoride, chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-Toluenesulfonate, preferably a singly negatively charged anion, more preferably an anion selected from the group consisting of fluoride, chloride, bromide, methanesulfonate and p-toluenesulfonate, most preferably bromide, optionally in the form of their racemates, enantiomers or hydrates.
  • anion selected from the group consisting of fluoride, chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate,
  • the compound of the formula AC-2 may also be present in the form of the free base AC-2-base.
  • Preferred corticosteroids are compounds which are selected from the group consisting of beclomethasone, betamethasone, budesonide, butixocort, ciclesonide, deflazacort, dexamethasone, etiprednol, flunisolide, fluticasone,
  • any reference to steroids includes reference to their optional salts or derivatives, hydrates or solvates.
  • Examples of possible salts and derivatives of steroids may be: alkali metal salts, such as, for example, sodium or potassium salts, sulfobenzoates, phosphates, isonicotinates, acetates, dichloroacetates, propionates, dihydrogen phosphates, palmitates, pivalates or even furoates.
  • Preferred PDE4 inhibitors here are compounds selected from the group consisting of enprofylline, theophylline, roflumilast, ariflo (cilomilast), tofimilast, pumafentrin, lirimilast, arofylline, atizoram, D-4418, bay 198004, BY343, CP-325,366, D-4396 (Sch-351591), AWD-12-281 (GW-842470), NCS-613, CDP-840, D-4418, PD-168787, T-440, T-2585, V- 11294A, Cl-1018, CDC-801, CDC-3052, D-22888, YM-58997, Z-15370 and
  • the acid addition salts of the betamimetics are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.
  • Preferred LTD4 antagonists here are compounds selected from the group consisting of montelukast, pranlukast, zafirlukast, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078 , VUF-K-8707, L-733321 and - l - (((R) - (3- (2- (6,7-Difluoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2- hydroxy-2-propyl) phenyl) thio) methylcyclopropane-acetic acid,
  • the acid addition salts of the betamimetics are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.
  • salts or derivatives which the LTD4-antagonists are capable of forming include: alkali metal salts, such as, for example, sodium or potassium salts, alkaline earth salts, sulfobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates ,
  • alkali metal salts such as, for example, sodium or potassium salts, alkaline earth salts, sulfobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates
  • EGFR inhibitors are preferably used compounds selected from the group consisting of cetuximab, trastuzumab, ABX-EGF, Mab ICR-62 and - 4 - [(3-chloro-4-fluorophenyl) amino] -6- ⁇ [4- (morph
  • the acid addition salts of the betamimetics are preferably selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate,
  • Hydrophosphate hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, Hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.
  • Preferred dopamine agonists are compounds selected from the group consisting of bromocriptine, cabergoline, alpha-dihydroergocryptine, lisuride, pergolide, pramipexole, roxindole, ropinirole, talipexole, terguride and viozan, optionally in the form of their racemates, enantiomers , Diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates.
  • Hydroiodide hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.
  • Hl antihistamines here are preferably compounds used, which are selected from the group consisting of epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, Mizo lastin, ketotifen, emedastine, dimetindene, clemastine, bamipine, Cexchlorpheniramin, pheniramine, doxylamine, Chlorphenoxamine, dimenhydrinate, diphenhydramine, promethazine, ebastine, desloratidine and meclocine, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates.
  • the acid addition salts of the betamimetics are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.
  • inhalable macromolecules can be used as disclosed in EP 1 003 478.
  • the compound may be derived from the group of derivatives of ergot alkaloids, the triptans, the CGRP inhibitors, the phosphodiesterase V inhibitors, optionally in the form of their racemates, enantiomers or diastereomers, optionally in the form of their pharmacologically acceptable acid addition salts, their solvates and / or hydrates.
  • the material for the powder inhaler according to the invention is preferably polymer compositions containing at least one thermoplastic polymer, at least one dehydrating agent and optionally at least one elastomer and / or optionally plasticizer and / or further fibers.
  • the material contains neither gelatin, nor cellulose or starch or derivatives thereof.
  • preferred polymer compositions comprise from 60% to 80% by weight of one or more thermoplastic polymers
  • the amount of dehydrating agent is 10 to 40% by weight, more preferably 20 to 30% by weight.
  • thermoplastic polymers are suitable, for example polystyrenes, polyolefins, polyamides, polyvinyl chlorides or polyurethanes.
  • Particularly preferred are polyethylene (Hostalen), in particular polyethylene with a density between 900 and 1000 kg / m 3 , preferably from 940 to 980 kg / m3, particularly preferably from 960 kg / m3 (high-density polyethylene), polycarbonate, polyester, polypropylene or polyethylene terephthalate.
  • Suitable dehydrating agents are, for example, silica gels, zeolites, aluminum oxide, magnesium sulfate, molecular sieves and the like.
  • the polymer composition can also contain other inorganic or organic additives which have the following function: plasticizer, stabilizer, dye, pigment or the like.
  • official regulations for example, DAB (Deutsches Arzneibuch)
  • the dewatering material has no pronounced adhesion to pharmaceutic-chemical substances, especially particles of respirable size. This ensures a more accurate dosage, in particular of the respirable fine fraction of the pharmaceutical preparation.
  • the wall of the inhaler component may contain regions of different polymer / dehydrator composition.
  • the wall of the inhaler component consists of at least two layers, an inner and at least one overlying outer layer.
  • One layer of the inhaler component then consists of a polymer composition without dehydrating agent, the other layer contains a dehydrating agent.
  • the powder inhaler according to the invention offers advantages when it is necessary to protect active ingredients, auxiliaries or formulations against water absorption in particular. For example, this applies to inhalable powders which have been prepared by spray-drying and / or to active ingredients, auxiliaries and formulations which are in the amorphous state.
  • An inventive and particularly preferred inhaler is for example a device of the HandiHaler ® brand as disclosed for example in EP 1342483rd
  • a preferred embodiment of this aspect of the invention relates to an ensemble of an inhaler for the inhalation of powdered medicaments and a two-part capsule, the inhaler being characterized by a) an upwardly open, cup-shaped lower part, which has two opposite windows in the casing and b) a plate which covers the opening of the lower part and has a second hinge element, c) an inhalation chamber for receiving the capsule, which is formed perpendicular to the plane of the plate on the lower part facing side of the plate and on which a head movable against a spring is provided, the head being provided with two ground needles, d) an upper part with a mouth tube and a third hinge element, and e) a lid having a fourth hinge element, the hinge elements being one of the Lower part, two of the plate, three of the O parts and four of the lid are interconnected.
  • Table 2 Sum of masses and water uptake capacities of housing components incorporating the powder formulation from selected inhalers
  • Table 3 Water absorption capacity of the considered inhaler components in comparison to the permeation of water through the component wall
  • ⁇ p difference of water vapor pressure outside and inside the reservoir tank
  • A Surface of reservoir tank component t: Period of permeation (here assumed to be 30 days) d: Wall thickness of reservoir tank component
  • Dehydrator would protect the formulation of all inhalers, assuming an otherwise tight reservoir container. However, water permeating through the actual reservoir reservoir openings may also be bound by the use of dewatering materials in the high capacity container walls.

Abstract

L’invention concerne un inhalateur de poudre pour administrer des formulations pharmaceutiques sensibles à l’humidité.
EP08716990A 2008-02-20 2008-02-20 Inhalateurs de poudre Withdrawn EP2254630A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2008/052085 WO2009103336A1 (fr) 2008-02-20 2008-02-20 Inhalateurs de poudre

Publications (1)

Publication Number Publication Date
EP2254630A1 true EP2254630A1 (fr) 2010-12-01

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP08716990A Withdrawn EP2254630A1 (fr) 2008-02-20 2008-02-20 Inhalateurs de poudre

Country Status (5)

Country Link
US (1) US20110203586A1 (fr)
EP (1) EP2254630A1 (fr)
JP (1) JP2011512209A (fr)
CA (1) CA2716124A1 (fr)
WO (1) WO2009103336A1 (fr)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004012093A1 (de) 2004-03-05 2005-09-22 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverinhalator mit Merkanaldüse
DE102006044752A1 (de) * 2006-09-20 2008-04-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Kolbendosierer
US8648085B2 (en) 2007-11-30 2014-02-11 Boehringer Ingelheim International Gmbh 1, 5-dihydro-pyrazolo (3, 4-D) pyrimidin-4-one derivatives and their use as PDE9A mudulators for the treatment of CNS disorders
UA105362C2 (en) 2008-04-02 2014-05-12 Бьорингер Ингельхайм Интернациональ Гмбх 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators
AP2011005672A0 (en) 2008-09-08 2011-04-30 Boehringer Ingelheim Int Pyrazolopyrimidines and their use for the treatment of CNS disorders.
SI2400950T1 (sl) 2009-02-26 2019-09-30 Glaxo Group Limited Farmacevtske forlmulacije, ki obsegajo 4-((1 R)-2-((6-(2-((2,6- diklorobenzil)oksi)etoksi)heksil)amino)-1-hidroksietil)-2- (hidroksimetil)fenol
BRPI1011533A2 (pt) 2009-03-31 2016-03-29 Boehringer Ingelheim Int derivados de 1-heterocicil-1 5- diidro-pirazolo [3,4--d] pirimidin-4-ona e seu uso como moduladores de pde9a.
GB0921075D0 (en) 2009-12-01 2010-01-13 Glaxo Group Ltd Novel combination of the therapeutic agents
EP3053924A1 (fr) 2010-08-12 2016-08-10 Boehringer Ingelheim International Gmbh Dérivés de 6-cycloalkyl-1,5-dihydro-pyrazolo [3,4-d] pyrimidin-4-un et leur utilisation en tant qu'inhibiteurs de la pde9a
US8809345B2 (en) 2011-02-15 2014-08-19 Boehringer Ingelheim International Gmbh 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders
AU356657S (en) * 2014-01-28 2014-07-29 Lupin Ltd Inhaler
AU356644S (en) * 2014-01-28 2014-07-29 Lupin Ltd Inhaler
AU356658S (en) * 2014-01-28 2014-07-29 Lupin Ltd Inhaler
AU355712S (en) * 2014-02-20 2014-05-22 Lupin Ltd Part of inhaler
CA173518S (en) 2016-02-08 2017-09-01 Nicoventures Holdings Ltd Cartridge for an electronic cigarette
GB201605102D0 (en) 2016-03-24 2016-05-11 Nicoventures Holdings Ltd Mechanical connector for electronic vapour provision system
GB201605100D0 (en) 2016-03-24 2016-05-11 Nicoventures Holdings Ltd Vapour provision system
GB201605105D0 (en) 2016-03-24 2016-05-11 Nicoventures Holdings Ltd Vapour provision apparatus
GB201605101D0 (en) 2016-03-24 2016-05-11 Nicoventures Holdings Ltd Electronic vapour provision system
WO2018015712A1 (fr) 2016-07-22 2018-01-25 Nicoventures Holdings Limited Boîtier pour dispositif de fourniture de vapeur
PL3691620T3 (pl) 2017-10-05 2022-11-21 Fulcrum Therapeutics, Inc. Inhibitory kinazy p38 zmniejszają poziom ekspresji genu dux4 i dalszych genów do leczenia fshd
US10342786B2 (en) 2017-10-05 2019-07-09 Fulcrum Therapeutics, Inc. P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4013566A (en) * 1975-04-07 1977-03-22 Adsorbex, Incorporated Flexible desiccant body
AU570013B2 (en) * 1982-10-08 1988-03-03 Glaxo Group Limited Medicament inhaler
ATE68346T1 (de) * 1987-07-22 1991-11-15 Farvalsa Ag Feuchtigkeitsstabile feste valproinsaeurezubereitung und verfahren zu ihrer herstellung.
GB9015522D0 (en) * 1990-07-13 1990-08-29 Braithwaite Philip W Inhaler
FR2698289B1 (fr) * 1992-11-20 1995-01-27 Airsec Ind Sa Matières déshydratantes à base de polymères.
DE4318455A1 (de) * 1993-06-03 1994-12-08 Boehringer Ingelheim Kg Kapselhalterung
GB0015043D0 (en) * 2000-06-21 2000-08-09 Glaxo Group Ltd Medicament dispenser
GB0130857D0 (en) * 2001-12-22 2002-02-06 Glaxo Group Ltd Medicament dispenser
DE10202940A1 (de) * 2002-01-24 2003-07-31 Sofotec Gmbh & Co Kg Patrone für einen Pulverinhalator
US7258118B2 (en) * 2002-01-24 2007-08-21 Sofotec Gmbh & Co, Kg Pharmaceutical powder cartridge, and inhaler equipped with same
DE10244795A1 (de) * 2002-09-26 2004-04-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverinhalator
GB0312148D0 (en) * 2003-05-28 2003-07-02 Aventis Pharma Ltd Stabilized pharmaceutical products
GB0315889D0 (en) * 2003-07-08 2003-08-13 Aventis Pharma Ltd Stable pharmaceutical products
US20070053845A1 (en) * 2004-03-02 2007-03-08 Shiladitya Sengupta Nanocell drug delivery system
DE102004012093A1 (de) * 2004-03-05 2005-09-22 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverinhalator mit Merkanaldüse
SE0401654D0 (sv) * 2004-06-24 2004-06-24 Astrazeneca Ab A support structure for a medicament
DE102005022862A1 (de) * 2005-05-18 2006-12-14 Airsec S.A.S Kapseln für Inhalatoren
DE102006016903A1 (de) * 2006-04-11 2007-10-25 Boehringer Ingelheim Pharma Gmbh & Co. Kg Inhalator
EP1844805A1 (fr) * 2006-04-13 2007-10-17 Boehringer Ingelheim Pharma GmbH & Co.KG Inhalateur
DE102006044752A1 (de) * 2006-09-20 2008-04-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Kolbendosierer
US20090235929A1 (en) * 2008-03-19 2009-09-24 Marc Egen Powder inhalers

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009103336A1 *

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CA2716124A1 (fr) 2009-08-27

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