[0001] 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.
[0002] 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.
[0003] 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.
[0004] The present invention provides a container including outlet means, 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 outlet means are made from polyester.
[0005] 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.
[0006] 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.
[0007] 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, containers 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.
[0008] Inhalation devices for use in association with a pressurized aerosol cannister of
medicament provided with a valve have been used in the administration of medicaments
to the lung by inhalation for some time. A preferred type of container is therefore
a pressurized aerosol cannister provided with a valve. Pressurized aerosol cannisters
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.
[0009] Suitable valves for pressurized aerosol cannisters include metering valves, in particular
those described in European Patent Application No 143577, which application is incorporated
herein by reference.
[0010] When the container is a pressurized aerosol cannister provided with a valve, 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.
[0011] Containers 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.
[0012] When the pharmaceutically active compound is an inhalation medicament for administration
to the lung, we prefer the container also to hold a prophylactic anti-asthma agent.
Prophylactic anti-asthma agents include nedocromil sodium and sodium cromoglycate.
[0013] Suitable polyester materials for use in the invention include polyethylene terephthalate
and particularly polybutylene terephthalate.
[0014] A specific example of a container according to the invention is a pressurized aerosol
cannister provided with a valve, the cannister being made of aluminium and the valve
being 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 cannister containing the following formulation:

1. A container including outlet means, 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 outlet means are made from polyester.
2. A container according to claim 1, which is a pressurized aerosol cannister provided
with a valve.
3. A container according to claim 2, wherein the pharmaceutically active compound
is dispersed in a pharmaceutically acceptable aerosol propellant.
4. A container according to any one of the preceding claims, wherein the pharmaceutically
active compound is for administration to the lung by inhalation.
5. A container according to any one of the preceding claims, wherein the pharmaceutically
active compound is a phenylethylamine derivative.
6. A container according to any one of the preceding claims, wherein the pharmaceutically
active compound is reproterol.
7. A container according to any one of claims 4 to 6, which also holds a prophylactic
anti-asthma agent.
8. A container according to claim 7, wherein the prophylactic anti-asthma agent is
sodium cromoglycate.
9. A container according to any one of the preceding claims, wherein the polyester
is polybutylene terephthalate.
10. A medicament inhalation device comprising a container according to any one of
the preceding claims.