Improved containers for reactive pharmaceutical compounds

Abstract: There is provided a container including outlet means, which comprises plastics components and holds a pharmaceutically active compound having a primary or secondary amine group, in which some or all of the plastics components which come into contact with the pharmaceutically active compound during storage or release through the outlet means are made from polyester. The container avoids the risk of interaction product formation which exists with conventional containers having non-polyester plastics components. The container is particularly useful when the pharmaceutically active compound is an inhaled phenylethylamine derivative, such as reproterol.

Description: This invention relates to improved containers for reactive pharmaceutically active compounds, more particularly to improved containers for pharmaceutically active compounds having a primary or secondary amine group. It has been found that when pharmaceutically active compounds having a primary or secondary amine group come into contact with certain plastics materials, including polyformaldehydes which are conventionally used for producing the plastics components of pressurized aerosol containers provided with valves, an interaction product may be formed. Thus, when such compounds are stored in or dispensed from containers where they come into contact with such plastics materials, there is a danger that the interaction product may contaminate the compound. This is highly undesirable, as the contaminant is potentially toxic. European Patent Application 196288 discloses a dosage package comprising a container of thermoplastic material, e.g. polyethylene, polypropylene or polyester, from which a defined dosage can be dispensed by squeezing the package. The package is non-pressurised and does not have a valve. The application does not recognise the problem which may be encountered when pharmaceutically active compounds having a primary or secondary amine group come into contact with certain plastics materials conventionally used in pressurised aerosol canisters provided with valves. We have now found that pharmaceutically active compounds having a primary or secondary amine group do not form interaction products when they come into contact with polyester materials, and that when such compounds are stored in or dispensed from containers in which some or all of the plastics components with which they come into contact are made from polyester, interaction product contaminants are not produced or their level is significantly reduced. The present invention provides a pressurised aerosol canister provided with an outlet valve, which comprises plastics components and holds a pharmaceutically active compound having a primary or secondary amine group; characterized in that some or all of the plastics components which come into contact with the pharmaceutically active compound during storage or release through the valve are made from polyester. The pharmaceutically active compound may be present as a salt, including an acid addition salt formed with the amine group, for example a hydrochloride, hydrobromide or hydrosulphate. It will be appreciated by those skilled in the art that the pharmaceutically active compound will often be present as a component of a pharmaceutical formulation. It is particularly important that medicaments administered to sensitive organs such as the lungs should be as pure as possible. Because of the potential toxicity of the interaction product contaminant mentioned above, canisters according to the present invention are particularly useful in the storage and administration to the lungs by inhalation of pharmaceutically active compounds having a primary or secondary amine group. Inhalation devices for use in association with a pressurized aerosol canister of medicament provided with a valve have been used in the administration of medicaments to the lung by inhalation for some time. Pressurized aerosol canisters are often made from a metal, for example aluminium, in which case some or all of the components of the valve will be made of polyester. Suitable valves for pressurized aerosol canisters include metering valves, in particular those described in European Patent Application No 143577. The pharmaceutically active compound is desirably dispersed in a pharmaceutically acceptable aerosol propellant, for example a chlorofluorocarbon or a hydrofluorocarbon such as trifluorochloromethane, dichlorotetrafluoroethane or dichlorodifluoromethane. Of course, a mixture of such propellants may be used, and conventional aerosol formulation components may also be present, including a surfactant, for example sorbitan trioleate. Canisters according to the invention are particularly useful in the storage and administration of pharmaceutically active phenylethylamine derivatives, including those in which the phenyl ring is substituted by hydroxy. Examples of such compounds include isoprenaline, salbutamol, orciprenaline and particularly reproterol. When the pharmaceutically active compound in an inhalation medicament for administration to the lung, we prefer the canister also to hold a prophylactic anti-asthma agent. Prophylactic anti-asthma agents include nedocromil sodium and sodium cromoglycate. Suitable polyester materials for use in the invention include polyethylene terephthalate and particularly polybutylene terephthalate. A specific example of a pressurized aerosol canister according to the invention is one in which the canister is made of aluminium and the valve is that described in EP 143577 with reference to Figures 1 and 2, but with the circular cup (1) and valve bush (3) being made of polybutylene terephthalate, and the canister containing the following formulation: sodium cromoglycate 1.4663 % w/w reproterol hydrochloride 0.7331 sorbitan trioleate 0.5000 trifluorochloromethane 10.0000 dichlorotetrafluoroethane 13.0951 dichlorodifluoromethane 74.2055 100.0000

Claims: A pressurised aerosol canister provided with an outlet valve, which comprises plastics components and holds a pharmaceutically active compound having a primary or secondary amine group; characterized in that some or all of the plastics components which come into contact with the pharmaceutically active compound during storage or release through the valve are made from polyester. A canister according to claim 1, wherein the pharmaceutically active compound is dispersed in a pharmaceutically acceptable aerosol propellant. A canister according to claim 1 or 2, wherein the pharmaceutically active compound is for administration to the lung by inhalation. A canister according to any one of the preceding claims, wherein the pharmaceutically active compound is a phenylethylamine derivative. A canister according to any one of the preceding claims, wherein the pharmaceutically active compound is reproterol. A canister according to claim 4 or 5, which also holds a prophylactic anti-asthma agent. A canister according to claim 6, wherein the prophylactic anti-asthma agent is sodium cromoglycate. A canister according to any one of the preceding claims, wherein the polyester is polybutylene terephthalate. A medicament inhalation device comprising a canister according to any one of the preceding claims.

Inventors: BROWN KENNETH, BROWN, KENNETH
Applicants: FISONS PLC
Application year: 1991
Main classification: A61M15
IPC codes: A61J1