BG64861B1 - Special steel canister for aerosol dosing operating on propellant gas - Google Patents

Abstract

The invention relates to special steel corrosion-proof canister for aerosol preparations by a gas-propellant means applicable in gas operated inhalers. The canister contains an active component prescription composition. It is corrosion-proof to the active substance - preparations for inhalation therapy with fluoro hydrocarbon as gas forming means, possessing sufficient pressure and destruction stability and ensures the keeping quality of the stored preparations. Its tank comprises specially selected homogenous material. The canister has an active substance of prescription composition with an active component containing salt, acid, base or electrolyte with TG 134a and/or TG 227 as gas propeller means for inhalation therapy, comprising a tank and a cup with a valve. The tank is made of an alloy containing, in %, from 40.0 to 53.0 iron, from 23.0 to 28.0 nickel, from 19.0 to 23.0 chromium, 4.0-5.0 molybdenum, 0.0 to 2.0 manganese, 1.0-2.0 copper, 0.0-1.0 silicon, 0.0-0.045 phosphorous, 0.0-0.35 sulphur and 0.0-0.020 carbon.

Description

The present invention relates to a corrosion-resistant special steel container for aerosol dispensers containing a gas-forming agent for use in working gas inhalers. The container is intended to contain a formulation containing an active ingredient which is fluorocarbon-driven and is used in particular in medicine for the inhalation administration of drugs.

BACKGROUND OF THE INVENTION

In gas-inhaler inhalers, the active substances are stored in a cartridge-like container together with the gas-forming agent. These containers generally consist of an aluminum tank which is closed by a valve cup (cap) made of aluminum into which a valve is incorporated. One such container may be inserted as a cartridge into the inhaler and remain there permanently, or after use replaced with a new cartridge.

Since the early 1990s, following the Rio de Janeiro Conference, fluorochlorine hydrocarbons (FCKWs, CFCs), due to their ozone-depleting properties, have been controlled globally, which is why their use has been avoided as an alternative. The aim is to use fluorocarbons (FKW, HFA) for use in inhalers operating with a gaseous medium.

Currently, promising agents for such application are TG 134a (1,1,2,2trifluoroethane) and TG 227 (1,1,1,2,3,3,3-heptafluoropropane). Accordingly, existing inhalation therapy delivery systems need to be converted to hydrocarbon-free gas (FCKW) and new application systems and active substance developed.

It is surprisingly found that aluminum containers that are filled with fluorocarbons as a gaseous agent are not always resistant, and are at high risk of corrosion depending on the composition of the preparation. This is especially true for compositions containing electrolyte and / or free ions, in particular free halides.

Similar instabilities of aluminum containers when using fluorocarbons as a gaseous agent are observed when the preparations contain acidic or basic constituents, for example in the form of active substances, additives such as stabilizers, surfactants, flavor enhancers, antioxidants and the like.

US 5 340 838 discloses a high-grade stainless steel container that stores an electrolyte-free metered aerosol with fluorochlorine hydrocarbon (TG 22).

DE 41 12 303 describes a container of high quality steel intended for the storage of hydroglycerin-containing aqueous solutions. This container contains no fluorochlorine hydrocarbons.

It is known that fluorochlorine hydrocarbons should not be used as a gaseous agent because of their ozone depleting properties and this is controlled worldwide.

These known containers, as well as those described above, have a problem with the insufficient resistance and the risk of corrosion of the containers used so far. This is especially true for the storage of drug formulations with fluorocarbons as a gaseous agent, and particularly for compositions containing electrolyte and / or free ions, especially free halides.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a container for gas-inhaler inhalers which is corrosion-resistant with respect to the active substance-fluorocarbon inhalation therapy preparations, having sufficient pressure and rupture resistance and which maintains the quality of the stored preparations.

It is another object of the invention to provide a container for gas-inhaler inhalers whose reservoir consists of a specially selected homogeneous material.

It has surprisingly been found that a container consisting of a tank, a glass cup and a valve, wherein at least the tank is made up of certain alloys of special steel, solve the task in accordance with the present invention. These alloys contain constituents such as chromium (Cr), nickel (Ni), molybdenum (Mo), iron (Fe) and carbon (C). Such alloys may further comprise copper (Cu), manganese (Ma) and silicon (Si). Preferably, the tank contains one of these additives.

The object of the present invention is solved by a container comprising the active ingredient of a formulation with an active ingredient comprising a salt, acid, base or electrolyte with TG 134a and / or TG 227 as a propellant inhalation therapy gas, wherein the container consists of tank and valve cup with valve fitted therein. The tank is made of an alloy containing 40.0-53.0% iron, 23.0-28.0% nickel, 19.0-23.0% chromium, 4.0-5.0% molybdenum, 0.02 , 0% manganese, 1.0-2.0% copper, 0.0-1.0% silicon, 0.0-0.045% phosphorus, 0.0-0.035% sulfur and 0.0-0.020% carbon.

Preferably, the container according to the present invention is in which the alloy from which the tank is made is chromium 19.0-23.0%, nickel 24.0-26.0%, molybdenum 4.0-5.0%, copper 1 , 02.0%, manganese up to 2.0%, silicon up to 0.5% and carbon up to 0.02% with iron, being essentially a residual component.

The container according to the invention is preferably such that the valve cup is made of aluminum and is sealed tightly with a seal and / or other general seal relative to the inside of the tank.

Accordingly, the container according to the invention is such that the valve comprises one or more stainless steel springs, a valve stem, a metering chamber and a valve body, wherein the valve stem, the metering chamber and / or the valve body are made of steel, the alloy of the tank and / or plastic.

The container according to the invention is preferably configured so that the spring / s are made of stainless steel and the valve stem, the metering chamber and the valve body are made of polybugylene terephthalate.

Preferably a container in which the valve stem is insulated by seals with respect to the valve cup according to the invention.

It is preferred to have a container in which, according to the invention, the seal or seals are or are made of an ethylene / propylene / diene terpolymer.

The container according to the invention is preferably also designed such that the valve cup is made of the same alloys as the tank.

The container according to the present invention is configured such that the tank withstands a bursting pressure of more than 30000 hPa, preferably more than 100000 hPa.

Also preferred is a container according to the invention whose tank withstands a bursting pressure of more than 200,000 hPa.

It is advantageous to have a container according to the invention in which the tank has a wall thickness of 0.1 to 0.5 mm, preferably 0.15 to 0.35 mm.

Preferably, a container made according to the present invention, wherein the tank has a wall thickness of 0.19 to 3 mm.

The container according to another preferred embodiment of the present invention is such that the formulation contained therein has a pH value of 2.0 to 5.0.

It is advantageous for the container according to the invention to be constructed in such a way that the active substance of the formulation contains electrolytes, which are preferably selected from hydroxide ions, cyanide ions and / or halide anions.

A container according to the invention is then preferred in which the electrolytes are selected from fluoride, chloride, bromide or iodide.

The object of the present invention is also solved by a reservoir containing the active ingredient of an active ingredient formulation comprising a salt, acid, base or electrolyte with TG 134a and / or TG 227 as a propellant inhalation therapy agent consisting of an alloy , described above for the construction of the container tank.

The tank of the invention is such that it withstands a bursting pressure of more than 30000 hPa, preferably more than 100000 hPa.

Preferably, a tank which according to the invention is capable of withstanding a bursting pressure of more than 200,000 hPa.

The tank according to this aspect of the invention has a wall thickness of 0.1 to 0.5 mm, preferably 0.15 to 0.35 mm.

It is also advisable to construct a tank according to the invention having a wall thickness of 0.19 to 3 mm.

The tank according to the invention contains a formulation composition having a pH of 2.0 to 5.0.

It is advantageous to have a reservoir in which, according to the invention, the active substance of the mixture contains electrolytes, which are preferably selected from hydroxide ions, cyanide ions and / or halide anions.

The tank according to this aspect of the invention is then such that the electrolytes are selected from fluoride, chloride, bromide or iodide.

To achieve the object of the present invention, it is contemplated to use a container according to the first aspect of the invention or a tank according to the second aspect of the invention in an inhaler and / or to store the active substance of a formulation containing ethanol such as co-solvent and iatropic bromide, oxytropic bromide, tiotropic bromide, albuterol or fenoterol as active substance.

The use according to the third aspect of the present invention, the container or reservoir in an inhaler and / or storage of the active ingredient of a formulation is suitable for a composition comprising ethanol ipotropic bromide, oxytropic bromide or tiotropic bromide as the active substance.

It is contemplated to use the container and / or tank according to the invention for a formulation comprising citric acid.

It is advantageous to use a container and / or tank made according to the first two aspects of the present invention for a mineral acid-containing formulation.

The use described above is also appropriate when the formulation contains hydrochloric acid.

Explanations of the drawings attached

The invention will now be described in more detail with reference to the drawings in the accompanying drawings, according to which:

Fig. 1 shows a cross-sectional view of a container, tank cup and valve according to the present invention;

Figure 2 shows a cross-sectional view of a container in another embodiment of the valve cup and valve according to the invention.

Examples of carrying out the invention

1 is a cross-sectional view of container 1 according to the invention. The container consists of a container 2 for placing a drug substance and a valve cup 8 with a valve 9.

The shape and size of the container 1 corresponds to the prior art aluminum container.

Tank 2 consists of an alloy with one

component in% of: Iron from 40.0-53.0 Nickel 23,0-28,0 Chrome 19,0-23,0 Molybdenum 4,0-5,0 Manganese 0,0-2,0 Honey 1,0-2,0 Silicon 0,0-1,0 Phosphorus 0,0-0,045 Sulfur 0,0-0,035 and Carbon 0,0-0,020

This alloy was selected according to the material number 1.4539 of the German Metallurgical Company's Special Steel List.

One preferred alloy of this type has the following composition in%:

Chromium 19.0-21.0

Nickel 24.0-26.0

Molybdenum 4,0-5,0 Honey 1,0-2,0 Manganese up to 2.0 Silicon up to 0.5 and Carbon to 0.02, with the remainder the constituent is essentially iron.

In an almost identical alternative alloy, the molybdenum content is limited to 4.5-5.0%.

In an alternative embodiment, the tank 2 according to the invention consists of an alloy selected in accordance with No. 1.4404 of the material from the Steel List of the German Metallurgists Company.

The composition of the alloy in% is:

Steel from 60.0-72.0 Nickel 9,0-13,0 Chrome 17,0-21,0 Molybdenum 2,0-3,0 Silicon 0,0-1,5 Phosphorus 0,0-0,04 Sulfur 0.0-0.04 and Carbon 0,0-0,03 Another form of implementation, the voir 2 according to the invention consists of alloy having the following composition in%: Chrome 16,5-18,5 Nickel 11,0-14,0 Molybdenum 2,0-2,5

Carbon - maximum 0.03 and steel as the rest.

The alloys mentioned above are such that they are corrosion-resistant with respect to various liquefied fluorocarbons such as TG 134a (1,1,1,3-tetrafluorocarbon) and TG 227 (1,1,1,2,3,3,3- heptafluoropropane).

These include propellant preparations, with active agents, surfactants, cosolvents, stabilizers, complexing agents, flavor enhancers, antioxidants, salts, acids, bases or electrolytes, for example hydroxyl ions, cyanide ions and / or cyanide ions and / or cyanide ions, suitable for inhalation therapy. , such as fluoride, chloride, bromide or iodide.

The tank 2 is formed by a casing, which is made of one of the alloys described above. The tank 2 has four different zones which are flat or recessed bottom 3, a cylindrical section 4, which in the upper third passes into a narrow neck 5 and finally ends with a flange 6, which surrounds the opening 7.

The wall thickness of the tank 2 in one preferred embodiment is between 0.1 and 0.5 mm, preferably between 5 0.15 and 0.35 mm, particularly preferably from about 0.19 to 3.0 mm.

In one preferred embodiment, the tank 2 withstands a bursting pressure of more than 30,000 hPa, preferably 10 more than 100,000 hPa, especially more than 200,000 hPa.

The weight of the tank 2 in one preferred embodiment is 5-15 g, in another preferred embodiment 15 the weight is 7-10 g and in another preferred embodiment this weight is 7.9-8.7 Mr Rücker

In one also preferred embodiment, tank 2 has a volume of 5 to 50 ml. Another tank 2 has a volume of 20 10 to 20 ml and again another tank 2 has a volume of about 15 to 18 ml.

In the closed state, the tank 2, after being filled with the drug and the gaseous substance, is tightly closed with the valve 25 cup 8.

In one embodiment, the valve cup 8 is also made of corrosion-resistant material.

Preferably, in this embodiment, 30 are taken into account the abovementioned alloys for tank 2 and / or plastic materials of appropriate pharmaceutical quality.

In another preferred embodiment, the valve cup 8 is aluminum. In this case 35, a seal 10 is provided, which and / or the valve 9 are arranged in such a way that the valve cup 8 cannot by itself come into contact with the liquid present in the tank.

One preferred embodiment of the valve cup 8 is in accordance with that disclosed in document GB 2 324 121, and therefore its entire scope is referred to herein.

In the closed position of the container 1, the valve cup 8 grips the tank 2 along its flange 6.

In a preferred embodiment, the seal 10 seals the valve cup 8 along the 50 flange 6, wherein the seal 10 can be formed in the form of a ring or washer. Preferably a washer-shaped seal. It can be made of materials known in the art that are suitable for use with medicaments with fluorocarbons such as gaseous agents.

For example, thermoplastics, elastomers, materials such as neoprene, isobutylene, isoprene, butyl rubber, bun-rubber, nutrile-rubber, copolymers of ethylene and propylene, terpolymers of ethylene, propylene and diene (diolefin), for example butadiene, are suitable for this purpose. or fluorinated polymers. Preferred materials are ethylene / propylene diene terpolymer (EPDM).

A valve 9 is formed on the side of the tank oriented toward the inside of the tank 8 in such a way that the valve stem 12 passes through the valve cup 8 and exits on the other side. The valve 9 is seated tightly in the central opening of the seal 10. The seal 10 and the valve 9 together seal the valve cup with respect to the inside of the tank 2 so that it cannot come into contact with the liquid contained in the tank 2.

The valve 9 is constructed in such a way that any element that can come into contact with the liquid in the tank 2 is made of corrosion-resistant material with respect to this liquid.

The elements of the valve 9 are a spring or springs 11, a valve stem 12 which extends from the inside out and passes through the opening 17 of the valve cup 8, the metering chamber 13 and the valve body 14.

The spring 11 is made of steel, preferably a special spring steel. The other elements of the valve 9 may be made, for example, of steel or of the alloys described above and / or of plastic.

The valve stem 12, the metering chamber 13 and the valve body 14 are preferably made of plastic, especially preferably polyester, most preferably polybutyl ether phthalate.

As depicted in Figure 1, one or more additional seals 15 and / or 16 can be formed which prevent fluid or gas from escaping from inside the tank 2.

The additional seal 15 and / or 16 may / may also be / be positioned such that the liquid inside the tank 2 only contacts the shell of the tank 2 and the valve 9.

The additional seal 15 optionally seals the vertically movable stem 12 at the point where it penetrates the valve cup 8.

The additional seal ^ seals the valve stem 12 inside the valve 9 relative to the valve body 14 and / or the metering chamber 13.

In this way, the additional seals 15 and 16 prevent liquid or gas from leaking from inside the tank 2 along the outer surface of the valve stem 12, thus contacting the valve cup 8.

The additional seals 15 and 16 may be made of the same material from which the seal 10, preferably ethylene / propylene diene terpolymer, is made.

In one embodiment where the valve cup 8 is not aluminum and one of the corrosion-resistant materials mentioned above, it is not necessary that the seal 10, together with the valve 9, completely isolate the valve cup 8 with respect to the interior of the 2. Therefore, in this case, it is also unnecessary for the seal 10 and the valve 9 to be firmly in contact with each other.

In this case, there is one gap between the seal 10 and the valve 9. Then the seal 10 is positioned, for example, directly on the underside of the valve cup 8 and seals the edge of the valve cup 8 with respect to the flange 6 of the tank 2, wherein the additional seal 15 seals the opening 17 of the valve cup 8 with respect to the interior of the tank 2.

Figure 2 shows another embodiment of valve cup 8 with a valve 9 inserted therein. This embodiment is generally identical to the embodiment shown in Figure 1. A significant difference between the two forms of embodiment of valve cup 8 is that the seal 10 and the additional seal 15 of the exemplary embodiment of Figure 1 are combined into a seal 18.

The seal 18 encloses the underside of the valve disk. The figure shows that the valve body 14 is inserted into the seal 18. The valve stem 12 passes through the opening 19 of the seal 18, which lies directly below the opening 17 of the valve cup 8. The opening 19 is dimensioned in such a way that it seals the valve stem 12 with respect to valve cup 8. The seal material 18 is identical to that described for the seal 10.

The production of the tank 2 according to the invention is analogous to that known in the prior art for the manufacture of an aluminum container and others, according to which the tank 2 is made of sheet metal of the respective material, respectively of the respective alloy.

In the present invention, the tank 2 is stamped from the sheet metal of the above alloys of chromium (C 2), nickel (Ni), molybdenum (Mo), steel (Fe) and carbon (C) or an alloy that further contains copper (Cu). manganese (Mn) and silicon (Si).

The tank 2 according to the invention, respectively the container 1 of the tank and the valve cup 8 with valve 9 is particularly suitable for use with fluorocarbon containing propellant preparations.

Propellant preparations, which can preferably be used in conjunction with the invention, are published in WO 1994/013262, which is referred to herein in its entirety.

Of these, acid-stabilized and / or ethanol propellant preparations with 1,1,2,2-tetrafluoroethane (TG 134a) and / or 1,1,1,2,3,3,3-heptafluoropropane (TG 227) are particularly suitable. ) as a propellant, especially those containing ipropic bromide, oxytropium bromide, albuterol, tiotropic bromide or fenoterol and as active substance.

According to the active substance, inorganic and organic acids are suitable for stabilization. In addition to halogen acids, mineral acids are also mentioned as examples of inorganic acids: sulfuric acid, hydrochloric acid, nitric acid or phosphoric acid, and ascorbic acid or citric acid as an example of organic acids.

In the case of hydrochloric acid, the active substance is preferably an acid whose anion is identical to that of the salt of the active substance.

For all active substances and salts of active substances, citric acid is generally suitable, which is preferred.

The acid content is such that the pH of the preparation is between 1.0 and 7.0, preferably between 2.0 and 5.0 and especially preferably 3.5 by weight.

In the case of inorganic acids, the content is in the range of about 0.00002 to 0.01 N.

In the case of ascorbic acid, the preferred content is in the range of approximately 0.0045 to 5.0 mg / ml and in the case of citric acid in the range of 0.0039 to 27.7 mg / ml.

In addition, the preparations may contain ethanol as cosolvent. The preferred amount is 1.0 to 50.0% by weight of the formulation.

Preferred exemplary preparations which may be stored in container 1, respectively, tank 2 of the above kind are further cited:

Example 1. Hypotropic bromide monohydrate 0.001-2.5% by weight High-grade ethanol 0.001-50 wt. % TG 134a 50.0-99.0 wt. % Inorganic acid 0.01-0.00002 normal Water Example 2. Hypotropic bromide 0.0-5.0 wt. % monohydrate 0.001-2.5 wt. % High-grade ethanol 0.001-50 wt. % TG 134a 50.0-99.0 wt. % Ascorbic acid 0.015-5.0 mg / ml Water (purified) Example 3. Hypotropic bromide 0.0-5.0 wt. % monohydrate 0.0187 wt. % High-grade ethanol 15,0000 wt. % TG 134a 84,4773 wt. % Citric acid 0,0040 wt. % Water (purified) 0.5000 wt. % Total Example 4. 100,0000 wt. %

Ipatropium bromide monohydrate Ethanol, complete TG 134a

Citric acid Water (purified) total

Example 5.

Ipatropium bromide monohydrate

Ethanol, complete TG 134a

Citric acid Water total

0,0374 wt. % 15,0000 wt. % 84.4586 wt. %

0,0040 wt. %

0.5000 wt. %

100,0000 wt. %

0.0748 wt. % 15,0000 wt. % 84.4212 wt. %

0,0040 wt. %

0.5000 wt. %

100,0000 wt%

Example 6

Phenoterol hydrobromide 0.192 wt. %

Ethanol, complete TG 134a

Citric acid Water total

30,0000 wt. % 67,806 wt. % 0,002 wt. % 2,000 wt. % 100,0000 wt%

One method to fill a container with the appropriate preparation may be "Dual Stage Pressure Fill-Methode", "Single Stage Cold FillMethode" or "Single Stage Pressure Fill" -Methode ”(One-Step Filling Method).

Claims

Claims (28)

A container (1) containing the active ingredient of a prescription composition with an active ingredient comprising a salt, acid, base or electrolyte with TG 134a and / or TG 227 as a propellant for inhalation therapy, wherein the container (1) consists from a tank (2) and a valve cup (8) with a valve (9) placed therein, characterized in that the tank (2) is made of an alloy containing in%: 40,0-53,0 iron, 23 , 0-28.0 nickel, 19.0-23.0 chromium, 4.0-5.0 molybdenum, 0.0-2.0 manganese, 1.0-2.0 copper, 0.0-1, 0 silicon, 0.0-0.045 phosphorus, 0.0-0.035 sulfur and 0.0-0.020 carbon. Container (1) according to claim 1, characterized in that the alloy from which the reservoir (2) is made is in%: chromium 19.0-23.0, nickel 24.0-26.0, molybdenum 4.0-5.0, copper 1.0-2.0, manganese up to 2.0, silicon up to 0.5, and carbon up to 0.02 with iron, being essentially a residual component. Container (1) according to claims 1 and 2, characterized in that the valve cup (8) is made of aluminum and is closed 5 tightly with seal (10) and / or (18) relative to the inside of the tank (2). Container (1) according to claims 1 to 3, characterized in that the valve (9) contains one or more springs (11) of non- 1 o stainless steel, valve stem (12), metering chamber (13) and valve body (14), wherein the valve stem (12), metering chamber (13) and / or valve body (14) are made of steel, and the alloys are the same as those of the reservoir (2) and / or plastic. Container (1) according to claims 1 to 4, characterized in that the spring (s) (11) are made of stainless steel and the valve stem (12) is a metering chamber (13) 20 and the valve body (14) are made of polybutylene terephthalate. Container (1) according to claims 1 to 5, characterized in that the valve stem (12) is insulated by seals (15) 25 or (18) with respect to the valve cup (8). Container (1) according to Claims 1 to 6, characterized in that the seal (10) and / or the seal (15) and / or the seal (18) is filled or filled by one Ethylene / propylene / diene terpolymer. Container (1) according to claims 1 to 7, characterized in that the valve cup (8) is made of the same alloys as the tank (2). 35 Container (1) according to claims 1 to 8, characterized in that the tank (2) withstands a destructive pressure of more than 30000 hPa, preferably more than 100000 hPa. Container (1) according to Claims 1 to 8, characterized in that the reservoir (2) withstands a bursting pressure of more than 200,000 hPa. Container (1) according to claims 1 to 10, characterized in that the container 45 (2) has a wall thickness of 0.1 to 0.5 mm, preferably 0.15 to 0.35 mm. Container (1) according to claims 1 to 10, characterized in that the container (2) has a wall thickness of 0.19 to 3 mm. 50 Container (1) according to claim 1 1 to 11, characterized in that the composition has a pH value of 2.0 to 5.0. Container (1) according to claims 1 to 13, characterized in that the active substance of the formulation contains electrolytes, which are preferably selected from hydroxide ions, cyanide ions and / or halide anions. Container (1) according to claim 14, characterized in that the electrolytes are selected from fluoride, chloride, bromide or iodide. 16. A reservoir containing the active ingredient of a prescription composition with an active ingredient comprising a salt, acid, base or electrolyte with TG 134a and / or TG 227 as a propellant for inhalation therapy, characterized in that it consists of an alloy, according to one of claims 1 and 2. A tank according to claim 16, characterized in that it withstands a bursting pressure of more than 30,000 hPa, preferably more than 100,000 hPa. 18. A tank according to claim 16, characterized in that it withstands a bursting pressure of more than 200,000 hPa. A tank according to claims 16 to 18, characterized in that it has a wall thickness of 0.1 to 0.5 mm, preferably 0.15 to 0.35 mm. 20. Tank according to claims 16 to 18, characterized in that it has a wall thickness of 0.19 to 3 mm. A tank according to claims 16 to 20, characterized in that the composition has a pH of 2.0 to 5.0. The tank according to claims 16 to 21, characterized in that the active substance of the formulation contains electrolytes, which are preferably selected from hydroxide ions, cyanide ions and / or halide anions. 23. A tank according to claim 22, characterized in that the electrolytes are selected from fluoride, chloride, bromide or iodide. Use of a container according to claims 1 to 15 or a container according to claims 16 to 23 in an inhaler and / or for storing the active substance of a formulation composition, characterized in that the formulation contains ethanol as cosolvent and iatropic bromide, oxytropic bromide, tiotropic bromide, albuterol or fenoterol as active substance. Use of a container according to claims 1 to 15 or a container according to claims 16 to 23 in an inhaler and / or for storing the active substance of a formulation, characterized in that the formulation comprises ethanol and ipropic bromide, oxytropic bromide or tiotropic bromide as the active substance. Use according to claim 24 or 25, characterized in that the formulation contains citric acid. Use according to claim 24 or 25, characterized in that the formulation contains a mineral acid. Use according to claim 24 or 25, characterized in that the formulation contains hydrochloric acid.