Patent Description:
In the case of vegetable liquid pharmaceutical forms, especially based on volatile oils, and in particular those containing lipophilic formulation components, storage instability can occur as a result of interactions with constituents of the primary packaging that are in continuous contact with the formulation, for example a liquid formulation stored in a sealed vessel. The product contact relates to both liquid and gaseous states of a product, and both states may be present within the same vessel or other storage container, as is a particular issue with plastic component of the vessel, for example a closure or cap. This problem is reinforced by a poorer ratio between the plastic surface area and the amount of liquid product contained in the vessel. As a result smaller volumes are more affected by this issue.

Due to the phenomenon of possible migration, lipophilic drug components can migrate into the primary packing material such as the vessel body, closure, or related elements such as a dropper or similar dosing system, which often project into the vessel from an underside of the closure or cap. Many of such drug components demonstrate a special affinity for polymer based materials.

This issue particularly affects so called "droppers" made of low density polyethylene (PE-LD) plastic, which droppers can dip directly into the product or the gas head space above the product, and thus show a high contact surface area. In addition the caps or closures from which the droppers extend, which can comprise high density polyethylene (PE-HD), show this phenomenon.

Both the dropper and cap are thus capable of absorbing active ingredients in such a way that it becomes a significant loss of active ingredient. This may occur during the storage period and can therefore vary depending on the time between initial packaging of the product and the end use by the consumer.

<CIT> discloses a dual compartment prescription pill container is provided. A first compartment that can function as a traditional prescription pill bottle has a closure that is engaged by a second, smaller compartment of a second container. The interior volume of each container can be accessed independently. The second container provides a receptacle in which a daily or weekly dosage of medicine may be housed to make it easier for a patient to determine if the day's dose was taken. Optionally, the second compartment can be removed to make it easier for a smaller quantity of medicine to be carried by a patient.

<CIT> discloses a dosing closure device for bottles, in particular for storing and dispensing liquid pharmaceuticals, comprises a multi-part cap closure mounted on the bottle neck including an inner cap with a mounting element for attachment to the bottle neck, an outer cap with a metering device, and a sealing membrane for closing the neck of the bottle.

The present invention has therefore been developed in order to avoid interactions between such liquid medicaments and their primary packaging.

According to a first aspect of the present invention there is provided a closure system for a medicament container according to claim <NUM>.

Preferably, the dosing element comprises a dropper.

Preferably, the adapter defines a first coupling operable releasable engage the primary closure member and a second coupling operable to releasably engage the secondary closure member.

Preferably, the first coupling is defined by a first end of the adapter and is dimensioned for a press fit over the primary closure member.

Preferably, the second coupling is defined by a second end of the adapted and is dimensioned for a press fit into the secondary closure member.

Preferably, the adapted defines a lumen extending between the first end and the second end.

Preferably, the secondary closure member at least partially comprises a material have an affinity for a product to be stored within the medicament container.

Preferably, the primary closure member comprises an occlusion element arranged to overlie a mouth of the medicament container.

Preferably, the occlusion element comprises at least a product contacting face having a low affinity for a product to be stored within the medicament container.

Preferably, the occlusion element comprises a sealing disc have an aluminium or polyethylene layer defining the product contacting face.

Preferably, the adapted is a contrasting colour to the primary closure member and the secondary closure member.

As used herein, the term "product" is intended to mean a substance, composition or active ingredient contained therein, for use as a medicament.

The present invention will now be described with reference to the accompanying drawings, in which:.

Referring now to the accompanying drawings there is illustrated a container closure system, generally indicated as <NUM>, for use in sealing a vessel <NUM> which contains, in use, a medicament or other liquid composition, for example a vegetable liquid pharmaceutical composition, in particular based on volatile oils, for example containing lipophilic components which are prone to storage instability as detailed above. It will however be appreciated that the closure system <NUM> of the present invention may be used to fill any number of alternative vessels or containers (not shown), containing various other liquids or liquid compositions, and need not be limited to use with liquid medicaments.

In the particular embodiment illustrated the vessel <NUM> comprises a glass bottle having a mouth <NUM> formed at the free end of a threaded neck <NUM> of the vessel <NUM>, via which the mouth <NUM> the liquid composition contained within the vessel <NUM> may be accessed or dispensed. The use of glass for the vessel <NUM> avoids the absorption of the liquid composition or active ingredient into the material forming the vessel <NUM>, and it will therefore be appreciated that any other suitable material or form may be chosen for the vessel <NUM>. It will of course also be understood that the threaded neck <NUM>, providing a mechanism by which the vessel <NUM> may be sealed via the closure system <NUM>, may be replaced with any other suitable functional alternative which allows the closure system <NUM> to be releasably secured to the vessel <NUM> as hereinafter described.

The closure system <NUM> comprises a primary closure member <NUM> which in the embodiment illustrated is in the form of a conventional threaded cap comprising a top <NUM> which in use overlies the mouth <NUM> when the primary closure member <NUM> is engaged about the threaded neck <NUM>, and a cylindrical sidewall <NUM> depending from the top <NUM>. An internal surface of the sidewall <NUM> is threaded to engage with the threaded neck <NUM> in order to releasably secure the primary closure member <NUM> to the vessel <NUM> in conventional fashion. The primary closure member <NUM> additionally incorporates a sealing disc <NUM> on the underside of the top <NUM>, the ceiling disc <NUM> being provided with a laminated aluminium layer on the product facing side in order to minimise or eliminate absorption of the product and/or active ingredient into the material forming the primary closure member <NUM> while the primary closure member <NUM> is secured to the vessel <NUM>, for example during storage and before the user has opened the vessel <NUM> and begun using the medicament or other liquid solution contained therein. As an alternative it will be appreciated that the primary closure member <NUM> itself, or at least the product facing surface of the top <NUM>, is formed from a material which does not absorb the medicament or active ingredient therein.

The primary closure member <NUM> additionally comprises, in the embodiment illustrated, a tamper evident ring <NUM> frangibly secured to the lower circumferential edge of the sidewall <NUM> and which, in conventional fashion, is separated from the sidewall <NUM> during the act of the first removal of the primary closure member <NUM> from the vessel <NUM>. It will be appreciated that any other tamper evident seal may be employed, or indeed may be omitted as required.

In the preferred embodiment illustrated the primary closure member <NUM>, in particular the top <NUM> and sidewall <NUM>, are formed from a low density polyethylene, but any other suitable material or combination of materials may be employed.

The closure system <NUM> additionally comprises a secondary closure member <NUM> which is arranged to be releasably engaged with the vessel <NUM> about the threaded neck <NUM> in a similar manner to the primary closure member <NUM>. The secondary closure member <NUM> comprises a top <NUM> depending from which is a cylindrical sidewall <NUM>, an internal surface of which is threaded to engage with the threaded neck <NUM>. Integrated with the secondary closure member <NUM> is a dosing element in the form of a dropper <NUM> which is of conventional design and operation known in the art, and as a result no further description of the configuration and operation thereof is considered necessary.

The dropper <NUM> may be released from within the secondary closure member <NUM> in order to be used in extracting a dose of the medicament or other liquid composition from within the vessel <NUM>, to be administered or otherwise dispensed from the dropper <NUM>, again in conventional fashion. The dropper includes a stem <NUM> which, when the dropper <NUM> is secured within the secondary closure member <NUM>, projects downwardly beyond the free end of the cylindrical sidewall <NUM>. As a result the dimensions of the stem <NUM> prevent the use of a sealing disc similar to the sealing disc <NUM>, were the secondary closure member <NUM> and integrated dropper <NUM> fitted directly to the vessel <NUM> at the point of filling the vessel <NUM> with the medicament or other liquid composition. The dropper <NUM> and the interior surface of the secondary closure member <NUM> would be in contact with the medicament or other liquid composition, whether directly or with a gaseous phase off the composition in the head space existing within the sealed vessel <NUM>, thereby resulting in absorption of the medicament or active ingredient into the material forming the dropper <NUM> and/or secondary closure member <NUM> during storage of the filled vessel <NUM> prior to use.

In order to overcome this problem the closure system <NUM> of the invention additionally comprises an adaptor <NUM> which is arranged to releasably secure the secondary closure member <NUM> to the primary closure member <NUM> while the primary closure member is in sealing engagement with the vessel <NUM>. The adapter <NUM> thus permits the use of the sealing disc <NUM> with the primary closure member <NUM>, while maintaining the dropper <NUM> out of contact with the liquid composition within the vessel <NUM>. The adaptor <NUM> comprises a substantially cylindrical sidewall <NUM> defining a first or lower end <NUM> and a second or upper end <NUM>, each of which are shaped and dimensioned to provide a complimentary and engaging fit with the primary closure member <NUM> and secondary closure member <NUM> respectively and as hereinafter described. The adaptor <NUM> is hollow thereby defining a lumen or chamber <NUM> therein which is dimensioned to entirely contain the stem <NUM> of the dropper while the secondary closure member <NUM> is secured to the primary closure member <NUM> via the adaptor <NUM>.

In the preferred embodiment illustrated the first end <NUM> has an internal diameter approximately equal to the external diameter of the upper end of the primary closure member <NUM> such that a press fit between the first end <NUM> of the adaptor <NUM> and the primary closure member <NUM> may be achieved, thereby allowing the adaptor <NUM> to be releasably engaged above the primary closure member <NUM> as illustrated in <FIG> and <FIG>. The second end <NUM> of the adaptor <NUM> is stepped inwardly with respect to the sidewall <NUM> such as to define an external diameter substantially equal to the internal diameter of the open end of the sidewall <NUM> of the secondary closure member <NUM>. In this way the second end <NUM> of the adaptor can achieve a press fit internally of the secondary closure member <NUM>, as clearly visible in <FIG>, the sidewall <NUM> of the adaptor <NUM> being of sufficient height to fully accommodate the stem <NUM> within the lumen <NUM> when the adaptor <NUM> is secured to both the primary closure member <NUM> and the secondary closure member <NUM>. In this way the stem <NUM> and indeed entire dropper <NUM> are sealed within the internal lumen or chamber <NUM> and are therefore inaccessible and so protected from contact and/or damage during storage of the vessel <NUM>.

It will be appreciated that any other suitable functional alternative to the press fit arrangements hereinbefore described may be provided between the ends of the adaptor <NUM> and the primary closure member <NUM> and secondary closure member <NUM>. For example a threaded engagement may be provided therebetween.

Thus in use the vessel <NUM> is filled with a liquid composition, whether an medicament or otherwise containing an active ingredient, and the primary closure member <NUM> releasably secured to the neck <NUM>, with or without the sealing disc <NUM> as hereinbefore described, in order to occlude the mouth <NUM> and thus contain the contents within the vessel <NUM> such as to prevent or minimise absorption of the product or active ingredient into the material forming the primary closure number <NUM>.

The adaptor <NUM> is then pressed onto the primary closure member <NUM> and the secondary closure member <NUM> then pressed onto the adaptor <NUM> such that the dropper <NUM> is contained within the lumen <NUM>. The combined closure system <NUM> and vessel <NUM> may then be located within any other suitable external packaging (not shown) or the like for transport and/or storage prior to use by the consumer or other end user. The end user will then remove the secondary closure member <NUM> from the adaptor <NUM>, and also remove the adaptor <NUM> from the primary closure member <NUM>. The primary closure member <NUM> may then be unscrewed from the vessel <NUM> and discarded, along with the adaptor <NUM>, the secondary closure member <NUM> then being screwed onto the vessel <NUM> to act as the combined closure and dropper. In this way the secondary closure member <NUM> and dropper <NUM> can be formed from conventional materials such as low density polyethylene, while avoiding the potential for product absorption during the storage phase of the medicament or other liquid composition.

Claim 1:
A closure system (<NUM>) for a medicament container (<NUM>), the closure system comprising a primary closure (<NUM>) adapted for releasably sealing the medicament container; a secondary closure member (<NUM>) adapted for releasably sealing the medicament container and comprising ar integrated dosing element; and an adapter (<NUM>) arranged to releasably secure the secondary closure member to the primary closure member when the primary closure member is in sealing engagement with the container, the adapter defining a chamber (<NUM>) for receiving the dosing element, the chamber being located such as to be inaccessible when the secondary closure member is secured to the primary closure member with the adapter.