KR20080110866A - Packaging means for multi-dose powder inhalers with optimized discharging properties - Google Patents

Abstract

The invention relates to a package for pharmaceutical mixtures or formulations for use in a powder inhaler. ® KIPO & WIPO 2009

Description

Packaging means for multi-dose powder inhalers with optimized discharging properties}

The present invention relates to a package for pharmaceutical composition, mixture or formulation for use in powder inhalers.

Medical aerosol therapy intended for lung inhalation using nebulizers, metered-dose aerosols or powder inhalers plays an important role in the treatment of many lung diseases.

In the field of powder inhalers, single- and multi-dose devices are known. Multi-dose powder inhalers are in the form of a power supply that takes a single dose from one well via a built-in metrology unit, or is stored together in the device (eg, the amount packaged in a blister). In the form of a pre-measured package single dosage form, individually disposed (eg, in the form of a capsule) for use in the device.

In particular, in a multi-dose powder inhaler, the means of packaging the powder formulation in the device is of great importance for the quality of the product and thus the suitability for inhalation use.

Accordingly, the main purpose of the package is to keep the chemical composition of the environment in the package constant to prevent or stabilize physical or chemical changes to the pharmaceutical composition, mixture or formulation.

In such situations, the short term stability (“stability in use”) that the pharmaceutical compositions, mixtures or formulations should essentially have, even if not adequately protected by the package, and the long term stability, ie, in the unopened package of the pharmaceutical composition, mixture or formulation As far as possible there is a difference between the stability to be guaranteed.

It is also important that the patient receive the inhalation formulation in the correct dosage upon inhalation.

The term "particulate dosage" refers to the dosage that reaches the patient's lungs. The particulate dosage is influenced by the interaction of the finely divided particles of the active substance with each other and with the excipients.

In particular, it is also known that as a result of changes in the level of moisture in the package, this interaction can be increased to significantly reduce the particulate dosage. Such changes also include the penetration of moisture into the package and the removal of moisture within the package.

The package will also have a shape and opening pattern (i.e. the portion of the package that is allowed to open or cut blisters) to allow for optimal air supply and thereby optimal distribution of pharmaceutical compositions, mixtures or formulations. It is necessary.

Examples of multi-dose powder inhalers are known in the art. For example, a powder inhaler consisting of a cup-shaped bottom part and the same cup-shaped lid is known from published European Patent Publications 0 703 800 B1 or 0 911 047 A1. After placing the capsule in the capsule holder, the patient interacts with one or more pins that can penetrate into the capsule holder by pressing the actuation component to start from a stationary state. The capsule is punctured by the pin (s) to release the medicament. Thus, for example, German Laid-Open Patent Publications 3348370 and 3336486 further disclose an inhaler comprising a disc shaped blister comprising many wells arranged in a circle. The individual wells each contain a dosage of the inhaled planned drug powder. The wells are closed at both sides with, for example, a sealing film. The cavity is opened to distribute the pharmaceutical powder. The opened well is connected to the inlet of the inhaler through an air channel. As an example, the inhaler of German Patent Publication No. 3336486 will be described in more detail. This includes a blank with a chamber (feed chamber) containing an air inlet and a disc shaped round blister with a medicine bag filled therein. The blister is loosely connected to a rotatable circular disc. Around the disc, holes are formed that are axially connected to the medicine bag (ie, the bag and the holes are disposed above and below each other). The chamber has an air outlet. The inhaler also has a piston which is opened by opening the medicine bag and allowing the medicine to be released into the chamber and sucked through the suction port. See drawings of this patent application and US patent specification.

For packages of drug powder, a difference occurs between the first package and the second package. The first package is characterized in direct contact with the inhalation formulation. The first package may optionally be surrounded by a second package which is a second, outer shield. The first package may be, for example, a capsule, a solid or flexible blister with wells, or a disc containing wells.

The second package can be a blister, bag, bag or other container. In general, the second package surrounds the first package as a whole. The second package is used especially when the first package is not suitable for protection from moisture.

The first package and any second package also have the task of protecting the active substance and the entire inhalable formulation from chemical or physical changes such that the inhalable formulation remains stable for a long time. Physical changes in question can, in particular, affect the distribution of the planned particulate dosage.

The choice of a suitable material for the package is determined by two factors. One is that the substance must be able to perform the necessary protective action. Another is that the material must be made into a package in the form necessary for use in a powder inhaler so that it can perform the expected function.

The underlying challenge of the present invention is to optimize the shape of the package, the perforation pattern of the package and the level of filling of the pharmaceutical composition, mixture or formulation in order to improve the distribution of the pharmaceutical composition, mixture or formulation.

This challenge is solved with a package according to claim 1. A further advantageous feature is the subject of the auxiliary claims.

Description of invention

The present invention therefore relates to a package for inhalation powder which has optimized the form, perforation pattern and level of filling of the pharmaceutical composition, mixture or formulation.

Detailed description of the invention

The present invention enables improved airflow and thereby improved distribution of pharmaceutical compositions, mixtures or formulations, with the aid of the form of the opening pattern in the perforation pattern of the package and the level of filling of the pharmaceutical composition, mixture or formulation. To the above-described optimized package. Preferably, the package consists of a capsule, blister, blister disc or blister strip. These different forms (except capsules) are referred to all below as blisters.

In general, the capsule consists of two parts, the capsule body (body) and the capsule lid (cap), and fit inside each other. However, multi-part capsules are also known. Preferably capsules of size 2 to 4 are used, most preferably capsules of size 3.

The capsule material is a non-digestible plastic or gelatin, in particular hard gelatin. The blister disc can be, for example, a cylinder-like disc that is 5 mm or less in height and 15 cm or less in diameter. In the disc there is a depression or well (well) formed perpendicular to the plane of the disc. Discs of this kind can be installed, for example, in inhalers according to German Patent Publication No. 3348370 or 3336486. This type of inhaler has a shield containing a disc-shaped circular blister with a filled medicine bag. The inhaler, among other things, includes a pin that opens one medicament bag and is arranged to allow the medicament to be released into the chamber and sucked through the inlet.

The shape of the package according to the invention, including the shape of the well, is essentially determined by the powder inhaler to be used. Preferably, the package is teardrop-shaped or oval or in the form of number 8. The inlet surface and outlet surface (s) are as far from each other as possible.

First of all, the blister package includes a thermoplastic element and a base element composed of two or more wells separated from each other by a net. The wells may be opened on more than one side and two opposite sides may be opened. This opening is blocked in a package ready for use, for example by a sealing foil attached to the substrate element.

The package can be made of standard commercialized materials. Preferably, it may be made of a plastic material. Most preferably, the material is used as a plastic selected from thermoplastic polymers such as polystyrene, polyolefins, polyamides, polyvinyl chlorides, polyethylenes, polycarbonates, polyesters, polypropylenes, polyethylene terephthalates or polyurethanes. They have the necessary rigidity or flowability to enable the mechanical task of the first package to be carried out. Also suitable are natural materials (such as gelatin) or synthetic materials of plastics and metals (such as aluminum), for example.

According to the invention, it is preferred, but not necessary, that all walls of the wells are made of the same material. In the wells, at least the wall blocking the opening can be made of a different material than the other walls.

Further information on the composition or process can be found in the prior art, in particular in EP 599690, 432438 or 400460.

The level of filling of the pharmaceutical composition, mixture or formulation in a package can be optimized and depends on the fluidity of the pharmaceutical composition, mixture or formulation.

The term fluidity refers to the ability of a pharmaceutical composition, mixture or formulation to flow as easily as a substance. In the art, the fluidity ff _c is

ff _c = σ ₁ / σ _c

Is defined as

Where σ ₁ is the solidification tension and sigma _c is the bulk strength. In general, fluidity is measured using a ring shear device.

For pharmaceutical compositions, mixtures or formulations with poor or no fluidity, the fluidity follows the formula 4 ≧ ff _c > 1. In this case, a partially filled package is used such that there is a free passage of air between one or more inlets and outlets. The flow formula for an easily flowing pharmaceutical composition, formulation or mixture is 4 <ff _c . In this case, a partially filled package is used so that there is a free passage of air between one or more inlets and outlets, or a fully filled package is used to enable an advantageous (simple and cheap) filling process. In the latter case, the filling volume is determined by the shape of the package and does not require any special metrology procedure.

Examples of pharmaceutical compositions, formulations or mixtures include all inhalable compounds, such as inhalable polymers disclosed in EP 1 003 478.

The following compounds can be used in the device according to the invention on their own or in combination. In the following compounds, W is a pharmacologically active substance, for example betamimetics, cholinergic agents, corticosteroids, PDE4-inhibitors, LTD4-antagonists, EGFR-inhibitors, dopamine agonists, H1-antihistamines , PAF-antagonists and PI3-kinase inhibitors. In addition, double or triple combinations of W can be combined and used in the device according to the invention. For example, the combination of W is

W represents betamimatic in combination with choline inhibitors, corticosteroids, PDE4-inhibitors, EGFR-inhibitors or LTD4-antagonists,

W represents a choline inhibitor in combination with a betamimatic, corticosteroid, PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist,

W represents a corticosteroid in combination with a PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist,

W represents a PDE4-inhibitor in combination with an EGFR-inhibitor or LTD4-antagonist,

W represents an EGFR-inhibitor combined with LTD4-antagonist.

Compounds used as betamimatics include albuterol, apomoterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, phenoterol, formoterol, hexoprelinin, ibuterol, isotarin, Isoprelinin, Levosalbutamol, Mabuterol, Meluadrin, Metaproterenol, Ossiprelinin, Perbuterol, Procaterol, Leproterol, Limiterol, Litodrin, Salmephamol, Salmeterol, Bovine Terenol, sulfonterol, terbutalin, tiaramid, tolubuterol, ginterol, CHF-1035, HOKU-81, KUL-1248 and

3- (4- {6- [2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino] -hexyloxy} -butyl) -benzyl-sulfonamide

5- [2- (5.6-diethyl-indan-2-ylamino) -1-hydroxy-ethyl] -8-hydroxy-1 H-quinolin-2-one

4-hydroxy-7- [2-{[2-{[3- (2-phenylethoxy) propyl] sulfonyl} ethyl] -amino} ethyl] -2 (3H) -benzothiazolone

1- (2-fluoro-4-hydroxyphenyl) -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] ethanol

1- [3- (4-methoxybenzylamino) -4-hydroxyphenyl] -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] ethanol

1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-N, N-dimethylaminophenyl) -2-methyl -2-propylamino] ethanol

1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-methoxyphenyl) -2-methyl-2-propyl Amino] ethanol

1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-n-butyloxyphenyl) -2-methyl-2 -Propylamino] ethanol

1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- {4- [3- (4-methoxyphenyl) -1,2, 4-triazol-3-yl] -2-methyl-2-butylamino} ethanol

5-hydroxy-8- (1-hydroxy-2-isopropylaminobutyl) -2H-1,4-benzoxazin-3- (4H) -one

1- (4-amino-3-chloro-5-trifluoromethylphenyl) -2-tert-butylamino) ethanol

6-hydroxy-8- {1-hydroxy-2- [2- (4-methoxy-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] jade Photo-3-one

6-hydroxy-8- {1-hydroxy-2- [2- (ethyl 4-phenoxy-acetate) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] Oxazine-3-one

6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxy-acetic acid) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] jade Photo-3-one

8- {2- [1,1-dimethyl-2- (2.4.6-trimethylphenyl) -ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] jade Photo-3-one

6-hydroxy-8- {1-hydroxy-2- [2- (4-hydroxy-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] jade Photo-3-one

6-hydroxy-8- {1-hydroxy-2- [2- (4-isopropyl-phenyl) -1.1dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazine-3 -On

8- {2- [2- (4-ethyl-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazine -3-one

8- {2- [2- (4-ethoxy-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] jade Photo-3-one

4- (4- {2- [2-hydroxy-2- (6-hydroxy-3-oxo-3.4-dihydro-2H-benzo [1,4] oxazin-8-yl) -ethylamino ] -2-methyl-propyl} -phenoxy) -butyric acid

8- {2- [2- (3.4-difluoro-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] Oxazine-3-one

1- (4-ethoxy-carbonylamino-3-cyano-5-fluorophenyl) -2- (tert-butylamino) ethanol

2-hydroxy-5- (1-hydroxy-2- {2- [4- (2-hydroxy-2-phenyl-ethylamino) -phenyl] -ethylamino} -ethyl) -benzaldehyde

N- [2-hydroxy-5- (1-hydroxy-2- {2- [4- (2-hydroxy-2-phenyl-ethylamino) -phenyl] -ethylamino} -ethyl) -phenyl ] -Formamide

8-hydroxy-5- (1-hydroxy-2- {2- [4- (6-methoxy-biphenyl-3-ylamino) -phenyl] -ethylamino} -ethyl) -1 H-quinoline 2-on

8-hydroxy-5- [1-hydroxy-2- (6-phenethylamino-hexylamino) -ethyl] -1 H-quinolin-2-one

5- [2- (2- {4- [4- (2-Amino-2-methyl-propoxy) -phenylamino] -phenyl} -ethylamino) -1-hydroxy-ethyl] -8-hydroxy Roxy-1H-quinolin-2-one

[3- (4- {6- [2-Hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino] -hexyloxy} -butyl) -5-methyl-phenyl ] -Urea

4- (2- {6- [2- (2.6-Dichloro-benzyloxy) -ethoxy] -hexylamino} -1-hydroxy-ethyl) -2-hydroxymethyl-phenol

3- (4- {6- [2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino] -hexyloxy} -butyl) -benzylsulfonamide

3- (3- {7- [2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino] -heptyloxy} -propyl) -benzylsulfonamide

4- (2- {6- [4- (3-cyclopentanesulfonyl-phenyl) -butoxy] -hexylamino} -1-hydroxy-ethyl) -2-hydroxymethyl-phenol

N-adamantan-2-yl-2- (3- {2- [2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino] -propyl} -phenyl Preferred are any racemates, enantiomers, diastereomers of the compounds selected from) -acetamides and forms of any pharmaceutically acceptable acid addition salts, solvates or hydrates thereof. Acid addition salts of betamimatics according to the present invention are hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate Preference is given to selecting from hydrofumarates, hydrotartrates, hydroxysalates, hydrosuccinates, hydrobenzoates and hydro-p-toluenesulfonates.

Choline inhibitors used are tiotropium salts, preferably bromide salts, oxytropium salts, preferably bromide salts, flutropium salts, preferably bromide salts, ipratropium salts, preferably bromide salts, glyco Pyrium salts, preferably bromide salts, thromium salts, preferably chloride salts, tolterodine compounds are preferred. Among the salts described above, the cation is pharmacologically active ingredient. The salts described above as anions are preferably chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, malate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzo Ate or p-toluenesulfonate, chloride, bromide, iodide, sulfate, methanesulfonate or p-toluenesulfonate are preferred as counter-ions. Of all the salts, chloride, bromide, iodide and methanesulfonate are particularly preferred.

Other preferred anticholinergic agents are selected from salts of formula AC1,

Here, X ⁻ represents an anion having a monovalent negative charge, preferably fluoride, chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, malate, acetate, citrate, fumarate , Anion selected from tartrate, oxalate, succinate, benzoate and p-toluenesulfonate, preferably having a monovalent negative charge, particularly preferably fluoride, chloride, bromide, methanesulfonate and p- Anion selected from toluenesulfonates, particularly preferably bromide in the form of their racemates, enantiomers or hydrates. Of particular interest are such pharmaceutical combinations containing isomers of the formula AC1en.

Here, X ⁻ may have the above meaning. Other preferred anticholinergic agents are selected from salts of formula AC2,

Wherein R represents methyl or ethyl and X ⁻ may have the meanings described above. In alternative embodiments, the compound of formula AC2 may be present in the form of the free base of formula AC2base.

Other specific compounds include:

-Trophenol 2,2-diphenylpropionate methobromide,

-Scopine 2,2-diphenylpropionate methobromide,

-Scopine 2-fluoro-2,2-diphenylacetate methobromide,

Trophenol 2-fluoro-2,2-diphenylacetate methobromide;

-Trophenol 3,3 ', 4,4'-tetrafluorobenzylate methobromide,

-Scopine 3,3 ', 4,4'-tetrafluorobenzylate methobromide,

-Trophenol 4,4'-difluorobenzylate methobromide,

Scopin 4,4'-difluorobenzylate methobromide,

-Trophenol 3,3'-difluorobenzylate methobromide,

Scopin 3,3'-difluorobenzylate methobromide;

Trophenol 9-hydroxy-fluorene-9-carboxylate methobromide;

Trophenol 9-fluoro-fluorene-9-carboxylate methobromide;

Scopine 9-hydroxy-fluorene-9-carboxylate methobromide;

Scopin 9-fluoro-fluorene-9-carboxylate methobromide;

Trophenol 9-methyl-fluorene-9-carboxylate methobromide;

Scopine 9-methyl-fluorene-9-carboxylate methobromide;

Cyclopropyltropin benzylate methobromide;

Cyclopropyltropin 2,2-diphenylpropionate methobromide;

Cyclopropyltropin 9-hydroxy-xanthene-9-carboxylate methobromide;

Cyclopropyltropin 9-methyl-fluorene-9-carboxylate methobromide;

Cyclopropyltropin 9-methyl-xanthene-9-carboxylate methobromide;

Cyclopropyltropin 9-hydroxy-fluorene-9-carboxylate methobromide;

Cyclopropyltropin methyl 4,4'-difluorobenzylate methobromide.

Trophenol 9-hydroxy-xanthene-9-carboxylate methobromide;

Scopine 9-hydroxy-xanthene-9-carboxylate methobromide;

Trophenol 9-methyl-xanthene-9-carboxylate-methobromide;

Scopin 9-methyl-xanthene-9-carboxylate-methobromide;

Trophenol 9-ethyl-xanthene-9-carboxylate-methobromide;

Trophenol 9-difluoromethyl-xanthene-9-carboxylate methobromide;

Scopin 9-hydroxymethyl-xanthene-9-carboxylate methobromide.

In addition, the above-mentioned compounds may be used as salts within the scope of the present invention, in which a meto-X salt may be used in place of metobromide, where X may have the meaning given for X ⁻ described above.

Examples of corticosteroids include beclomethasone, betamethasone, budesonide, butyxocoat, ciclesonide, diplazacoat, dexamethasone, etiprednol, flunisolide, fluticasone, loteprednol, mometasone, Prednisolone, prednisone, lopleponide, triamcinolone, RPR-106541, NS-126, ST-26 and

(S) -fluoromethyl 6,9-difluoro-17-[(2-furanylcarbonyl) oxy] -11-hydroxy-16-methyl-3-oxo-androstar-1,4- Diene-17-carbothionate

(S)-(2-oxo-tetrahydro-furan-3S-yl) 6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxy-androstar-1 , 4-diene-17-carbothionate,

Cyanomethyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α- (2,2,3,3-tetramethylcyclopropylcarbonyl) oxy-androstar-1, Preference is given to using compounds selected from 4-diene-17β-carboxylates, optionally in the form of their racemates, enantiomers, diastereomers and optionally their salts and derivatives, their solvates and / or hydrates. . Anything referring to a steroid includes any salt or derivative, hydrate or solvate thereof that may be present. Examples of possible salts and derivatives of steroids are: alkali metal salts, such as sodium or potassium salts, sulfobenzoates, phosphates, isonicotinates, acetates, dichloroacetates, propionates, dihydrogen phosphates, palmitates, pivalates or Furoate can be mentioned.

PDE4-inhibitors that may be used include enpropylline, theophylline, roflemilast, ariflo (silomilast), topimillast, pumapentrin, lirimilast, arophylline, artizora, 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

N- (3,5-dichloro-1-oxo-pyridin-4-yl) -4-difluoromethoxy-3-cyclopropylmethoxybenzamide

(-) p-[(4aR *, 10bS *)-9-ethoxy-1,2,3,4,4a, 10b-hexahydro-8-methoxy-2-methylbenzo [s] [1, 6] naphthyridin-6-yl] -N, N-diisopropylbenzamide

(R)-(+)-1- (4-bromobenzyl) -4-[(3-cyclopentyloxy) -4-methoxyphenyl] -2-pyrrolidone

3- (cyclopentyloxy-4-methoxyphenyl) -1- (4-N '-[N-2-cyano-S-methyl-isothioureido] benzyl) -2-pyrrolidone

Cis [4-cyano-4- (3-cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid]

2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxy-phenyl) cyclohexan-1-one

Cis [4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-ol]

(R)-(+)-ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidine-2-ylidene] acetate

(S)-(-)-ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidine-2-ylidene] acetate

9-cyclopentyl-5,6-dihydro-7-ethyl-3- (2-thienyl) -9H-pyrazolo [3.4-c]-1,2,4-triazolo [4.3-a] pyridine

9-cyclopentyl-5,6-dihydro-7-ethyl-3- (tert-butyl) -9H-pyrazolo [3.4-c] -1,2,4-triazolo [4.3-a] pyridine Preferred are the forms of any racemate, enantiomer, diastereomer of the compound selected from among them, and any pharmaceutically acceptable acid addition salts thereof, solvates and / or hydrates thereof. Acid addition salts of PDE4 inhibitors according to the invention are hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydro Preference is given to selecting from fumarate, hydrotartrate, hydroxideate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.

LTD4-antagonists used are montelukast, franlukast, jasperlukast, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078, VUF-K-8707 , L-733321 and

1-(((R)-(3- (2- (6,7-difluoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl ) Phenyl) thio) methylcyclopropane-acetic acid

1-(((1 (R) -3 (3- (2- (2,3-dichlorothieno [3,2-b] pyridin-5-yl)-(E) -ethenyl) phenyl)- 3- (2- (1-hydroxy-1-methylethyl) phenyl) propyl) thio) methyl) cyclopropaneacetic acid

Any racemate, enantiomer, diastereomer of a compound selected from [2-[[2- (4-tert-butyl-2-thiazolyl) -5-benzofuranyl] oxymethyl] phenyl] acetic acid Preferred are the forms of and any of the pharmaceutically acceptable acid addition salts, solvates and / or hydrates thereof. Such acid addition salts according to the present invention are hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate Preference is given to selecting from hydrotartrate, hydroxideate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate. Examples of salts and derivatives that LTD4-antagonists may optionally form include: alkali metal salts, such as sodium or potassium salts, alkaline earth metal salts, sulfobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates , Palmitate, pivalate or furoate.

EGFR-inhibitors that can be used include cetuximab, trastuzumab, ABX-EGF, Mab ICR-62 and

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (morpholin-4-yl) -1-oxo-2-buten-1-yl] -amino} -7 Cyclopropylmethoxyquinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-diethylamino) -1-oxo-2-buten-1-yl] -amino}- 7-cyclopropylmethoxy-quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] -amino} -7 Cyclopropylmethoxyquinazoline

4-[(R)-(1-phenyl-ethyl) amino] -6-{[4- (morpholin-4-yl) -1-oxo-2-buten-1-yl] -amino} -7 Cyclopentyloxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6-{[4-((R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo -2-buten-1-yl] amino} -7-cyclopropylmethoxy-quinazolin

4-[(3-chloro-4-fluoro-phenyl) amino] -6-{[4-((R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo- 2-buten-1-yl] amino} -7-[(S)-(tetrahydrofuran-3-yl) oxy] -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6-{[4-((R) -2-methoxymethyl-6-oxo-morpholin-4-yl) -1- Oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxy-quinazoline

4-[(3-Chloro-4-fluoro-phenyl) amino] -6- [2-((S) -6-methyl-2-oxo-morpholin-4-yl) -ethoxy] -7 -Methoxy-quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-({4- [N- (2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2-butene -1-yl} amino) -7-cyclopropylmethoxy-quinazolin

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] -amino} -7 Cyclopentyloxy-quinazoline

4-[(R)-(1-phenyl-ethyl) amino] -6-{[4- (N, N-bis- (2-methoxy-ethyl) -amino) -1-oxo-2-butene -1-yl] amino} -7-cyclopropylmethoxy-quinazolin

4-[(R)-(1-phenyl-ethyl) amino] -6-({4- [N- (2-methoxy-ethyl) -N-ethyl-amino] -1-oxo-2-butene -1-yl} amino) -7-cyclopropylmethoxy-quinazolin

4-[(R)-(1-phenyl-ethyl) amino] -6-({4- [N- (2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2-butene -1-yl} amino) -7-cyclopropylmethoxy-quinazolin

4-[(R)-(1-phenyl-ethyl) amino] -6-({4- [N- (tetrahydropyran-4-yl) -N-methyl-amino] -1-oxo-2- Buten-1-yl} amino) -7-cyclopropylmethoxy-quinazolin

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7- ((R) -tetrahydrofuran-3-yloxy) -quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7- ((S) -tetrahydrofuran-3-yloxy) -quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-({4- [N- (2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2-butene -1-yl} amino) -7-cyclopentyloxy-quinazolin

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N-cyclopropyl-N-methyl-amino) -1-oxo-2-buten-1-yl] amino } -7-cyclopentyloxy-quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7- [(R)-(tetrahydrofuran-2-yl) methoxy] -quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7- [(S)-(tetrahydrofuran-2-yl) methoxy] -quinazoline

4-[(3-ethynyl-phenyl) amino] -6.7-bis- (2-methoxy-ethoxy) -quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -7- [3- (morpholin-4-yl) -propyloxy] -6-[(vinyl-carbonyl) amino] -quinazoline

4-[(R)-(1-phenyl-ethyl) amino] -6- (4-hydroxy-phenyl) -7H-pyrrolo [2,3-d] pyrimidine

3-cyano-4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] Amino} -7-ethoxy-quinoline

4-{[3-chloro-4- (3-fluoro-benzyloxy) -phenyl] amino} -6- (5-{[(2-methanesulfonyl-ethyl) amino] methyl} -furan-2 Quinozoline

4-[(R)-(1-phenyl-ethyl) amino] -6-{[4-((R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo-2 -Buten-1-yl] amino} -7-methoxy-quinazolin

4-[(3-chloro-4-fluorophenyl) amino] -6-{[4- (morpholin-4-yl) -1-oxo-2-buten-1-yl] -amino} -7 -[(Tetrahydrofuran-2-yl) methoxy] -quinazoline

4-[(3-chloro-4-fluorophenyl) amino] -6-({4- [N, N-bis- (2-methoxy-ethyl) -amino] -1-oxo-2-butene -1-yl} amino) -7-[(tetrahydrofuran-2-yl) methoxy] -quinazoline

4-[(3-ethynyl-phenyl) amino] -6-{[4- (5.5-dimethyl-2-oxo-morpholin-4-yl) -1-oxo-2-buten-1-yl] Amino} -quinazoline

4-[(3-Chloro-4-fluoro-phenyl) amino] -6- [2- (2.2-dimethyl-6-oxo-morpholin-4-yl) -ethoxy] -7-methoxy- Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [2- (2.2-dimethyl-6-oxo-morpholin-4-yl) -ethoxy] -7-[(R )-(Tetrahydrofuran-2-yl) methoxy] -quinazoline

4-[(3-Chloro-4-fluoro-phenyl) amino] -7- [2- (2.2-dimethyl-6-oxo-morpholin-4-yl) -ethoxy] -6-[(S )-(Tetrahydrofuran-2-yl) methoxy] -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {2- [4- (2-oxo-morpholin-4-yl) -piperidin-1-yl]- Methoxy} -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [1- (tert-butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quina Sleepy

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (trans-4-amino-cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (trans-4-methanesulfonylamino-cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (tetrahydropyran-3-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-methyl-piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(morpholin-4-yl) carbonyl] -piperidin-4-yl-oxy} -7- Methoxy-Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(methoxymethyl) carbonyl] -piperidin-4-yl-oxy} -7-methoxy- Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (piperidin-3-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [1- (2-acetylamino-ethyl) -piperidin-4-yloxy] -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (tetrahydropyran-4-yloxy) -7-ethoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6-((S) -tetrahydrofuran-3-yloxy) -7-hydroxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methoxy-ethoxy) -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {trans-4-[(dimethylamino) sulfonylamino] -cyclohexane-1-yloxy} -7-methoxy- Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {trans-4-[(morpholin-4-yl) carbonylamino] -cyclohexane-1-yloxy} -7 -Methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {trans-4-[(morpholin-4-yl) sulfonylamino] -cyclohexane-1-yloxy} -7 -Methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (tetrahydropyran-4-yloxy) -7- (2-acetylamino-ethoxy) -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methanesulfonylamino-ethoxy) -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(piperidin-1-yl) carbonyl] -piperidin-4-yloxy} -7- Methoxy-Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-aminocarbonylmethyl-piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4- {N-[(tetrahydropyran-4-yl) carbonyl] -N-methyl-amino}- Cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4- {N-[(morpholin-4-yl) carbonyl] -N-methyl-amino} -cyclo Hexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4- {N-[(morpholin-4-yl) sulfonyl] -N-methyl-amino} -cyclo Hexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (trans-4-ethanesulfonylamino-cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-ethoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7- (2-methoxy-ethoxy)- Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [1- (2-methoxy-acetyl) -piperidin-4-yloxy] -7- (2-methoxy -Ethoxy) -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4-acetylamino-cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-ethynyl-phenyl) amino] -6- [1- (tert-butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quinazoline

4-[(3-ethynyl-phenyl) amino] -6- (tetrahydropyran-4-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4- {N-[(piperidin-1-yl) carbonyl] -N-methyl-amino}- Cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4- {N-[(4-methyl-piperazin-1-yl) carbonyl] -N-methyl- Amino} -cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {cis-4-[(morpholin-4-yl) carbonylamino] -cyclohexane-1-yloxy} -7 -Methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1- [2- (2-oxopyrrolidin-1-yl) ethyl] -piperidin-4-yloxy } -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7- ( 2-methoxy-ethoxy) -quinazoline

4-[(3-ethynyl-phenyl) amino] -6- (1-acetyl-piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-ethynyl-phenyl) amino] -6- (1-methyl-piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-ethynyl-phenyl) amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-methyl-piperidin-4-yloxy) -7 (2-methoxy-ethoxy) -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-isopropyloxycarbonyl-piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4-methylamino-cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {cis-4- [N- (2-methoxy-acetyl) -N-methyl-amino] -cyclohexane-1- Yloxy} -7-methoxy-quinazoline

4-[(3-ethynyl-phenyl) amino] -6- (piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-ethynyl-phenyl) amino] -6- [1- (2-methoxy-acetyl) -piperidin-4-yloxy] -7-methoxy-quinazoline

4-[(3-ethynyl-phenyl) amino] -6- {1-[(morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(cis-2,6-dimethyl-morpholin-4-yl) carbonyl] -piperidine-4 -Yloxy} -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(2-methyl-morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(S, S)-(2-oxa-5-aza-bicyclo [2,2,1] hept -5-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazolin

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(N-methyl-N-2-methoxyethyl-amino) carbonyl] -piperidine-4- Yloxy} -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-ethyl-piperidin-4-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(2-methoxyethyl) carbonyl] -piperidin-4-yloxy} -7-methoxy Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- {1-[(3-methoxypropyl-amino) -carbonyl] -piperidin-4-yloxy} -7 -Methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [cis-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexane-1-yloxy] -7 -Methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [cis-4- (N-acetyl-N-methyl-amino) -cyclohexane-1-yloxy] -7-meth Toxy-Quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (trans-4-methylamino-cyclohexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [trans-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexane-1-yloxy] -7 -Methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (trans-4-dimethylamino-cyclohexane-1-yloxy] -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (trans-4- {N-[(morpholin-4-yl) carbonyl] -N-methyl-amino} -cyclo Hexane-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- [2- (2.2-dimethyl-6-oxo-morpholin-4-yl) -ethoxy] -7-[(S )-(Tetrahydrofuran-2-yl) methoxy] -quinazoline

4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline

Any of compounds selected from 4-[(3-chloro-4-fluoro-phenyl) amino] -6- (1-cyano-piperidin-4-yloxy) -7-methoxy-quinazolin Preference is given to the forms of racemates, enantiomers, diastereomers and any pharmaceutically acceptable acid addition salts, solvates or hydrates thereof. Such acid addition salts according to the invention are hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate Preference is given to selecting from hydrotartrate, hydroxideate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.

The dopamine agonists used may be selected from bromocriptine, carvergoline, alpha-dihydroagocreatine, lisuride, pergolide, pramipexole, roxinedol, rofinirol, thalipexole, turgrid and biozan Preferred are the forms of any racemates, enantiomers, diastereomers and any pharmaceutically acceptable acid addition salts, solvates or hydrates thereof. Such acid addition salts according to the invention are hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, Preference is given to selecting from hydrotartrate, hydroxideate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.

H1-antihistamines that can be used include, efinastin, cetirizine, azelastine, fexofenadine, levocarbastine, loratadine, mizolastine, ketotifen, emedastine, dimethindene, clemastine, bamipine , Any of the racemates, enantiomers of a compound selected from mexclofeniramine, peniramine, doxylamine, chlorophenoxamine, dimenhydrinate, dipfenhydramine, promethazine, evastin, desloratidine, and meclozin , In the form of diastereomers and any pharmaceutically acceptable acid addition salts, solvates or hydrates thereof. Such acid addition salts according to the present invention are hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate Preference is given to selecting from hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.

It is also possible to use inhalable polymers, as described in EP 1 003 478.

In addition, the compounds are in the form of any racemates, enantiomers or diastereomers thereof from the group of ergot alkaloid derivatives, trytans, CGRP-inhibitors, phosphodiesterase-V inhibitors. And any pharmaceutically acceptable acid addition salts, solvates and / or hydrates thereof.

Examples of ergot alkaloid derivatives include dihydroergotamine and ergotamine.

Materials suitable for inhalation include salts and esters thereof and combinations of the above active materials, salts and esters, including pharmaceutical compositions, pharmaceutical formulations and mixtures with the active materials described above.

By way of example, the figures show different shapes of the individual wells of the capsule or blister (known generally as package means) and the corresponding puncture location.

The drawings illustrate this without limiting the scope of the invention.

1: Sphere or hemisphere, 5 hole-shaped inlets, 1 outlet

Figure 2: Sphere or Hemisphere, 4 Hole-Shaped Inlets, 1 Outlet

3: oval, 6 hole-shaped inlets, 1 outlet

4: oval, 5 hole-shaped inlets, asymmetric, 1 outlet

Figure 5: oval, three hole-shaped inlets, asymmetrical, one outlet

6: oval, two hole-shaped inlets

Figure 7: Dumbbell form, 2x3 hole-shaped inlets, one outlet

Figure 8: Dumbbell shape, 2x2 hole-shaped inlets, asymmetrical, one outlet

Figure 9: 8-character shape, 2x3 hole-shaped inlets, one outlet

Figure 10: 8-character shape, 2x2 hole-shaped inlets, asymmetrical, one outlet

Figure 11: Teardrop shape, three hole-shaped inlets, one outlet

Figure 12: Teardrop shape, 4 hole-shaped inlets, 1 outlet

13: Teardrop shape, crescent-shaped inlet, one outlet

Using standard powder (glass beads), the cavitation properties were measured by measuring the time spent cavitation for a given constant volume flow rate (corresponding to 10 L / min of air). Table 1 shows the different shapes of capsules or blisters. Inlets are indicated by small circles in the figures and outlets are indicated by large circles.

The results in Table 1 show that the cavitation properties of the package depend to a large extent on its shape and opening (s).

Flow rate of air through a commercial standard size package: 10 L / min.

The active material in its micronized form has a particle size of 1 to 5 μm. The powder mixture as well as the active substance also contains 200 m lactose.

The results in Table 2, for the active substances phenoterol and tiotropium,

a) residue left in the wells and

b) the cavitation time of the wells.

Depending on the shape and opening pattern of the wells of the package, the wells of the package with optimal air flow have significantly improved cavitation properties. Equation 0.5 <V <2 is applied to the ratio V (the ratio of the sum of the inflow surfaces divided by the sum of the outflow surfaces). Preferably, the sum of the inlet surfaces should be equal to the sum of the outlet surfaces.

Claims (12)

A package for a powder inhaler, characterized in that it can be opened to optimize the form of the package and the level of filling for the pharmaceutical composition, mixture or formulation, and the distribution of the pharmaceutical composition, mixture or formulation. The powder inhaler package according to claim 1, which is a capsule. Package for powder inhaler according to claim 2, characterized in that it is a capsule of size 2 to 4, preferably a capsule of size 3. The package of claim 1, which is a blister, a blister disc, a blister coil or a blister strip with one or more wells. The package for powder inhalers according to claim 1, wherein the sum of the inlet surfaces per well or capsule is equal to the sum of the outlet surfaces per well or capsule. The powder inhaler package according to any one of claims 1 to 5, wherein the well or capsule has a maximum flow rate of air passing through it. 7. The package of claim 1, wherein the well or capsule is in the form of a tear drop and the inlet surface and the outlet surface (s) are arranged at maximum intervals from each other. 8. The package for powder inhalers according to claim 1, wherein the wells or capsules are elliptical and the inlet surface and outlet surface (s) are arranged at maximum intervals from each other. 9. The package for powder inhalers according to any one of claims 1 to 8, characterized in that the wells or capsules are eight-shaped and the inlet and outlet surface (s) are arranged at maximum intervals from each other. 10. The package for powder inhaler according to claim 1, wherein the well or capsule has a shape as shown in FIGS. 1 to 13. 11. The package for powder inhalers according to claim 1, wherein the well or capsule has an opening pattern as shown in FIGS. 1 to 13. A powder inhaler comprising the package according to claim 1.

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