GB2345320A - Filling containers for metered dose dispensers - Google Patents

Abstract

The displacement of air with a compressible inert gas, such as nitrogen, is a means to reducing loss of prime. A method is disclosed of filling a pressurised dispensing container 2 for use with a metered dose dispensing apparatus 3 comprising the step of displacing air from a container having an open mouth by introducing a liquid product into the container body. The liquid product produces a vapour at room temperature and pressure to thereby displace said air. The container body is then sealed with a dispensing valve in the mouth of the container body. The sealed container is then pressure filled via the valve with more liquid product and further by introducing an inert compressed gas via the valve.

Description

IMPROVEMENTS IN FILLING CONTAINERS FOR METERED DOSE DISPENSERS The invention relates to improvements in filling containers for metered dose dispensers using the displacement of air with a compressible inert gas, such as nitrogen, as a means to reducing loss of prime.

The accuracy of a metered dose of an active drug is very important in dispensing drugs and medicaments and more attention is being paid nowadays to the consistent accuracy of every dose supplied by pharmaceutical dispensing means. One problem in particular which has been noted is the loss of prime.

This is usually characterised by the measure of the product (i. e. the complete formulation including the drug/medicament and carrier) which is dispensed from the valve following storage in adverse conditions and/or for an extended duration. This can equate to storage of the dispenser fitted with a valve intended for valve down usage, stored with the valve pointing upwards for up to 24 hours as this replicates the more severe aspects of patient usage. If the total amount of formulation dispensed is reduced, then it also follows that the amount of active substance dispensed is also below specification.

There are a number of explanations for loss of prime. The first is simply that the liquid drains out of the metered volume of the valve back into the storage container which is often referred to as"drain back". The principal factors controlling such drain back would be the flow path geometry and fluid properties such as surface tension and viscosity. A common approach adopted to improve drain back is to either restrict this flow path, or make the route more tortuous.

A second explanation is more complex and results from the thermodynamic properties of the liquified propellants normally employed in such dispensers and in particularly in metered dose inhalers. The propellants give off a vapour, consisting of molecules of substance. If the substance is in an enclosed space, as it is in a dispensing container, the pressure of the vapour will reach a maximum that depends on the nature of the substance and the temperature. Within the closed container, at room temperatures, such propellants are in an equilibrium state, in as much as molecules of the liquid are transforming into vapour at the same time as the reverse is occurring. The metered volume of product is connected to the bulk of the product and this vapourisation also occurs in the metering chamber. A significant expansion to the vapour state displaces liquid from the chamber, causing a loss of prime and this can occur if the dispenser is stored with the valve pointing either upwards or downwards. It is thought likely that the actual loss of prime occurs as a combination or interaction of these two phenomena.

Mechanical solutions to a loss of prime have been proposed by modifying the valve design as described in pending patent applications GB 9607314.3, GB 9608707.7 and GB 9701365. 0. These rely on modifying the valve design to physically restrict drain back or to provide a chamberless valve so that there is no prime to lose.

As an alternative solution to the loss of prime it is an object of the present invention to provide a method of filling a container for use with a metered dose dispenser which would help to cure loss of prime during storage.

Purging is a process which is already used with metered dose inhalers for the removal or replacement of trapped air, to thereby exclude oxygen and moisture during filling and therefore minimise degradation of the product during storage.

In a non-purged system the head space of the container is filled with propellant vapour and compressed air. In the filling operation for such a system the valve is positioned on an empty container, containing just air and crimped thereto. The container is then filled with the propellant such that the head space comprises air plus vapour.

Purging is achieved either via a vacuum or by the exclusion of the air with a liquifiable propellant.

In the traditional two stage self-purging system, a propellant (i. e. the drug and carrier) is placed in the empty container. As soon as the propellant liquid is released into the atmosphere it immediately starts evaporating and produces a vapour, occupying a volume hundreds of times the original liquid. A valve is placed in the mouth of the container and crimped thereto such that the propellant and vapour are sealed in a closed system. However in the self-purging system the container is subsequently pressure filled with more propellant which helps to purge any remaining air from the container during the filling process with the liquifiable propellant. However this process eliminates an additional pressure element which is normally found in non-purged systems.

When the metering chamber of a non-purged system is primed in the valve down position, it is filled with liquid with the net head space pressure acting on it. During the valve up storage orientation stage the net pressure continues to act on the chamber contents.

For loss of prime to occur it is thought that a vapour bubble is created within the chamber, this bubble consisting of propellant vapour only. For the vapour bubble to grow in the chamber, it will have to displace liquid into the main container which would further compress the compressible (air/nitrogen) element, which would require an increase in pressure.

This being the case the effective inclusion of a compressable gas is to reduce the probability of loss of prime occuring in the metered dose inhaling apparatus.

Another traditional method of filling comprises a single stage system with vacuum purging. The valve is placed on the empty container and the air withdrawn to create a vacuum. The valve is crimped in place and the container filled with propellant. This vacuum purging eliminates the presence of any air.

In another method, pressure purging is used prior to crimping. Again the valve is positioned on the empty container which is then purged with the propellant vapour to eliminate the air before crimping. The container is then subsequently filled with propellant.

Thus, in the prior art systems whilst purging is conducted on metered dose inhalers for a number of good reasons, not least of which is the exclusion of oxygen, the resulting purging can lead to increased loss of prime.

The present invention provides a solution to loss of prime utilising purging as a part of the filling process, but without the disadvantages known from the present purging system.

According to the invention there is therefore provided a method of filling a pressurised dispensing container for use with metered dose dispensing apparatus comprising the step of displacing air from a container body having an open mouth by introducing a liquid product into the container body, which liquid product produces a vapour at room temperature and pressure to thereby displace said air, sealing the container body with a dispensing valve in the mouth of the container body, pressure filling the sealed container via the valve with more liquid product, and further introducing an inert compressible gas via the valve.

The advantage of the present invention is that by purging the air (containing degradadable oxygen and moisture) and replacing it with a relatively inert compressible gas such as nitrogen which has a low solubility in the propellant system, the benefits with respect to loss of prime can be achieved that a compressed air element would normally provide whilst at the same time minimising the risk of degradation.

Preferred embodiments of the invention will now be described by way of example only, with reference to the accompanying drawing which is a sectional elevation of a pressurised dispensing container.

The pressurised dispensing container 1 has a cylindrical container body 2. A valve 3 is held in place on a rim of the container body 2 by means of a ferrule 4 which is crimped to the container body 2.

The valve 3 has a valve stem 5, an outer end of which projects from the valve 3 in an outward direction with respect to the container body 2 and has an inner end portion projecting from the valve 3 in an inward direction with respect to the container 2. The valve stem 5 is reciprocatingly slidable within a body of the valve 3. The valve 3 operates such that depression of the valve stem 6 causes a metered dose of a product, such as a drug or other medicament, is released via the valve stem 5.

In a first embodiment of the invention a container body 2 is first filled with a small amount of a liquid product 6. At ambient pressure and temperature the product begins to vapourise and the propellant vapour pushes the air out of the container body 2. When all the air has been driven out of the container body 2, a valve 3 is positioned in the mouth of the container body 2 and crimped thereto by means of a ferrule 4. The sealed container 1 is then pressure filled with more liquid product 6, in a known manner, via the valve stem 5. The product 6 comprises medicament or drugs and a propellant which acts as a carrier. The resulting head space 7 in the container is filled substantially with propellant vapour. To provide the compressability required to avoid the loss of prime problems identified above, a charge of an inert compressed gas, such as nitrogen, is introduced via the valve 3 which mixes with the vapour in the head space 7. Nitrogen has a higher relative density than air at ambient temperature and is a relatively inert gas which has a low solubility in the propellant system commonly used in such dispensers. The charge of nitrogen, another gas, advantageously also cleans through the valve following the filling operation.

In the method of the present invention nitrogen is the preferred gas used to substitute the air following the filling operation. However, any alternative relatively inert gas may be used as long as it has a low solubility in the product. A typical propellant system in which such a method may be used include CFC's, HFA's or HFC's.

Claims (5)

1. CLAIMS: 1. A method of filling a pressurised dispensing container for use with metered dose dispensing apparatus comprising the step of displacing air from a container body having an open mouth by introducing a liquid product into the container body, which liquid product produces a vapour at room temperature and pressure to thereby displace said air, sealing the container body with a dispensing valve in the mouth of the container body, pressure filling the sealed container via the valve with more liquid product, and further introducing an inert compressed gas via the valve.
2. 2. A method as claimed in claim 1 in which the gas is nitrogen.
3. 3. A method as claimed in any one of the preceding claims in which the product comprises a medicament and propellant, the propellant being selected from the group containing CFC's, HFA's and HFC's.
4. 4. A method as claimed in any one of the preceding claims in which the gas has low solubility in the liquid product.
5. 5. A method of filling a pressurised dispensing container for use with metered dose dispensing apparatus substantially as hereinbefore described with reference to and as shown in the accompanying drawing.