Note: Descriptions are shown in the official language in which they were submitted.
~WO 94/22722 21 ~i 8 a 7 ~ PCT/EP94/00921
G Method for filling aerosol contalners
.
The present invention relates to a method of removing air from
containers which are to be filled with a substance to be dispensed and with a
5 propellant. This removal of air is generally known as "purging" and will be so-
described in this application.
The invention particularly concerns a method of purging containers which
are to be filled with a suspension or solution of a substance, for example a
pharmaceutical material, in a propellant which is gaseous at room temperature
10 but is held under pressure in liquid form. Such a propellant is known as a high-
pressure propellant. This type of filling method is described in UK Patent
Publication No. 2236146. In this filling method, after the suspension is filled into
the container, an amount of high pressure propellant without the pharmaceutical
material therein is forced through the filling head, thereby cleaning the filling
15 head and ensuring that when the filling head is lifted no suspension can escape
into the atmosphere. The filling is conducted through the outlet valve of the
container, because high pressure propellants are involved.
When the valves are crimped onto the containers, before filling, the
containers are fuil of air. When the containers are filled, the air remains
20 trapped, though obviously under pressure. The presence of air does not assistin the action of the propellant to expel the substance on activation and can also
compror"ise the sterility of the contents if the air is not pure.
To operate the filling procedure under vacuum, thereby removing air
from the containers, is not feasible. The necessary equipment would be very
25 expensive, it is not possible to remove all air in this way, and in any case the
valves are not generally designed to withstand a vacuum or partial vacuum.
Purging of air from containers containing a liquid soap solution and a
volatile propellant is disclosed in US Patent 2684806. This patent discloses a
purging ,neli,od co,n,c,rising the steps of partially filling the open containers with
30 the soap solution and then introducing into the soap solution a gas which
expands the solution into a foam until it fills the container. The valve is thensealed onto the container and the volatile propellant is introduced through the
valve.
This purging system is obviously not approl,riate for the filling method
described in GB-A-2236146. The equivalent of the soap solution would be the
~g~
WO 94/22722 PCT/EP94/00921
suspension of pharmaceutical material in a high pressure propellant. Unlike the
soap solution this is volatile and in any case it is highly undesirable to have the
pharmaceutical material in open contact with the atmosphere. Even if high
pressure propellant alone were put into the open container this would
evaporate over time; even if the container were closed quickly movement of the
container to the valve fitting station would cause air turbulence and the
container would tend to entrain air into it.
Accor;li~,g to the invention there is provided a method of purging a
container which is to be filled with a substance to be dispensed and a high-
pressure propellant the purging method comprising the steps of:
placing a valve on the container without sealing it thereon;
introducing an amount of high-pressure propellant into the container;
allowing the high-pressure propellant to expand and force air in the
container out through the unsealed connection between the valve and the
container; and
sealing the valve onto the container.
The invention also provides an aerosol dispenser comprising a container
and a valve sealed to the cc "~iner wherein the container is purged and filled
by a method comprising the steps of:
placing a valve on the container without sealing it thereon;
introducing an amount of high-pressure propellant into the co"ldiner;
allowing the high pressure propellant to expand and force air in the
container out through the unsealed connection between the valve and the
container;
sealing the valve on to the conlai"er; and
introducing the substance to be dispensed and a further quantity of high-
pressure propellant into the container through the valve after the valve has been
sealed on to the container.
It has been found surprisingly that having the valve loose on the
container allows the evaporating high-pressure propellant to expel air out
around the valve while not allowing air back in. Although under-valve purging ispossible the high-pressure propellant is most advantageously filled into the
container through the valve.
It should be e""~hasised that the advantages of the purging method of
the invention do arise even for filling methods where the substance to be
~WO 94/22722 21~ ~ 0 7 ~ PCT/EP94/00921
dispensed is not in suspension or solution in a high-pressure propellant. In
known methods, the open container can be partly filled with a substance in a
low-pressure propellant (i.e. one which is liquid at room temperature). The
valve can then be placed on the container and the air purged as described
5 above, before sealing the valve and then introducing the final amount of high- pressure propellant through the valve.
An embodiment of the invention is described in more detail below, by
example only, with reference to the following drawing which shows,
schematically, a purging method according to the invention.
The drawing indicates three successive stations A, B and C of a purging
and filling process. At station A an empty conlainer 1 has a valve 2 simply
placed thereon; the valve is not sealed onto the container, so that a limited air
gap is left ar~und the top of the container.
At station B, a filling head 3 is lowered onto the container 1 and an
amount of high-pressure propellant is injected into the container. The amount
may be, for example, 0.29 of liquid propellant. The filling head 3 is not
described in detail since its construction will be well Ul ,der~loGd by those skilled
in the art; the filling head is equivalent to a standard gassing head with an
integral metering system.
The propellant drops to the bottom of the container and evaporates,
displacing air out of the container. In practice the propellant will be heavier than
air and so displaces the air from the bottom of the container upwards.
To prevent the pressure of the expanding propellant from tending to lift
off the valve, and in order to release that pressure, the filling head should belifted slowly off the valve, for example at a velocity of 20cm/s. After the head is
lifted off the valve, it can be retracted at a higher velocity.
At station C, the valve is crimped onto the container by a crimping head
4, in a conventional fashion.
The sealed container can now be moved to a filling station at which it can
be filled through the valve with a suspension of pharmaceutical substance in a
high-pressure propellant followed, optionally, by propellant alone to clean the
filling head.
The phar,llaceutical sl~,sl~.,ce can be, for example, 5~lhut~mol,
beclomethasone dipropionate, salmeterol or fluticasone propionate.
WO 94/22722 ~ 7 PCT/EP94/00921
The purging propellant can be the same as the filling propellant, for
example 1,1,1,2-tetrafluoroethane, i.e. propellant 134a.
The purging method described has been found to be extremely efficient,
because the valve is in place while purging occurs, loss of the propellant and
5 entrainment of air is avoided and, in addition, the air in the valve itself is purged.
