GB2481050A

GB2481050A - A pharmaceutical package allowing mixing of a solid and a liquid

Info

Publication number: GB2481050A
Application number: GB1009722.8A
Authority: GB
Inventors: Stephen Willgress
Original assignee: Athlone Laboratories Ltd
Current assignee: Athlone Laboratories Ltd
Priority date: 2010-06-10
Filing date: 2010-06-10
Publication date: 2011-12-14
Also published as: GB201009722D0

Abstract

A pharmaceutical package comprising two containers 2, 4, detachably connected together at the openings. The interior of one container contains a solid pharmaceutical composition and the other contains a suitable diluent. A sealing means is located at the mouth of one of the containers and a displacing means is included to displace the seal activated by relative movement. Preferably the relative movement is both axial on rotational through a threaded engagement of the containers necks 12, 10 with a hollow connecting member 14. There may be a seal over both container openings comprising a membrane 7, 9 and the hollow connecting member includes cutting elements 22, 24 to pierce the membrane when the containers are screwed into the connecting member.

Description

A PHARMACEUTICAL PACKAGE

This invention relates to a pharmaceutical package for use in preparing a liquid pharmaceutical composition and in particular a pharmaceutical suspension composition.

Background of the Invention

There are many circumstances where it is desirable or preferable to administer a drug substance or other pharmaceutical substance in a liquid form. Such circumstances include the administration of drugs to children or to patients who, for various reasons, are unable or unwilling to swallow capsules or tablets.

Whereas many pharmaceutical substances can be formulated as solutions or suspensions and have acceptable shelf lives when in solution or suspension, there are many other substances that are relatively unstable in solution over long periods. For drugs that are insoluble in water, it is often possible to prepare suspensions. However, excipients such as suspending agents and thickeners are typically required in order to prepare stable suspensions and, even with the inclusion of such excipients, suspensions may still suffer from poor long term stability.

For the above reasons, many drugs are manufactured and sold in a dispersible solid form and are then mixed with a liquid diluent such as sterile water shortly before use. For example, penicillin antibiotics such as amoxicillin and flucloxacillin are often supplied to pharmacists in powder form and are then made up into suspensions for immediate or short term use by patients.

Whereas making up a suspension formulation in a pharmacy does not usually pose any problems for a trained pharmacist, there is nevertheless potential for errors to be made, particularly if part-trained or untrained staff members are used to perform the task and are inadequately supervised. Making up suspensions can also be somewhat time consuming meaning that customers may have to wait longerfora prescription to be fulfilled. It would therefore be advantageous if compositions intended to made up into suspensions could be provided to the pharmacist in a form which requires shorter preparation times and which avoids the possibility of weighing and measuring errors within the pharmacy.

The extemporaneous preparation of liquid pharmaceutical formulations can also be highly problematic in circumstances where sterile water is in short supply or simply not available at all, for example in field hospitals and disaster relief operations. In such circumstances, rather than refuse to dispense potentially lifesaving drugs because there is no sterile water available, there will be a strong temptation or indeed a need for medical personnel to use water from a supply of potable water or other source of water that appears to be clean. In such circumstances, the presumed clean water may not in fact be clean and hence there exists ample opportunity for medicines to become contaminated by dirty or non-sterile water. In the case of antibiotics, there is also the possibility that some of the antimicrobial activity of the antibiotic will be used up by killing the bacteria present in the contaminated water, thus leaving the patient with a sub-potent medicine.The foregoing problems are exacerbated when there are not even adequate supplies of potable water available, as is frequently the case when supplying medical aid in natural disaster situations.

Summary of the Invention

The present invention sets out to provide a pharmaceutical package that overcomes many of the aforementioned problems.

Accordingly, in a first aspect, the invention provides a pharmaceutical package comprising first and second containers each having a mouth and an interior, the first and second containers being detachably connected together so that the mouths of the containers face one another: the interior of the first container having present therein a pharmaceutical composition in a dispersible solid form; the interior of the second container having present therein a liquid diluent; one or more sealing elements being positioned between the interior of the first container and the interior of the second container so as to prevent premature mixing of the pharmaceutical composition and the liquid diluent; wherein the package comprises means for displacing the one or more sealing elements so as to allow dispersion and mixing of the pharmaceutical composition and the liquid diluents; and wherein the means for displacing the one or more sealing elements is actuable by relative movement between the first and second containers.

Thus, the pharmaceutical package of the invention comprises, in one container, a pharmaceutical composition in dry dispersible form and, in another container, a liquid diluent for mixing with the dry dispersible composition to form a suspension or solution. The two containers are connected together so that the mouths of the two containers face one another and one or more sealing elements are positioned between the interiors of the two containers in order to prevent the contents of the two containers from mixing prematurely. The pharmaceutical package may be delivered in this form to a pharmacy or to the location where it is to be used.

The package is provided with a mechanism for displacing the sealing elements so that the pharmaceutical composition and liquid diluent can be mixed to form the desired liquid formulation. The mechanism is actuated by moving the two containers relative to one another, for example by pushing or screwing them together, the relative movement of the two containers serving to push a displacing element against a sealing element to displace the sealing element and open up a passageway between the interiors of the two containers.

The two containers may be connected together directly. For example, each container may have a neck and a main container body. The two containers may be connected together by direct attachment of the neck of one container to the neck of the other container; for example by virtue of a screw thread on the outer surface of the neck of one container engaging a complementary thread on the inner surface of the neck of the other container.

Alternatively, the two containers may be connected by means of a hollow connecting member which, when the sealing elements are displaced, provides a passageway from the interior of one container to the interior of the other container.

In one embodiment, at least one of the containers has a threaded neck which engages a thread at one end of the hollow connecting member.

For example, in one particular embodiment, both containers have threaded necks which engage threads at two opposed ends of the hollow connecting member.

The necks of the containers may be provided with external or internal threads to engage, respectively, internal or external threads on the hollow connecting member.

One or more sealing elements are provided to protect the contents of the first and second containers from premature mixing.

The sealing element may be positioned at the mouth of a container or in the hollow connecting member when present. Typically, the mouth of at least one of the containers is sealed by a sealing element. Preferably, the mouths of both containers are sealed by sealing elements.

Each sealing element can take the form of a membrane sealing the mouth of the container. The membrane may be formed from, for example, an aluminium/heat seal lacquer laminate formulated to heat seal to the neck of the container.

Means are provided to displace each sealing element to allow the contents of the first and second containers to mix when it is desired to prepare a liquid pharmaceutical formulation such as a suspension.

The term "displace" as used herein covers both complete displacement (in which the whole of the sealing element is displaced) and partial displacement (in which only part of the sealing element is displaced. For example, the sealing element may be partially displaced by cutting away part of the element or puncturing or otherwise perforating the sealing element.

The means for displacing the one or more sealing elements is located so that it may be actuated without the need first to separate the containers. Preferably, the means for displacing the one or more sealing elements is connected to or formed integrally with one or both of the containers and/or the hollow connecting member when present.

The means for displacing the one or more sealing elements may comprise one or more formations having an edge or a point (preferably an edge) for cutting or piercing the sealing element.

For example, the displacing means may comprise a cutting member which cuts through at least part of the sealing element when the two containers are subjected to relative movement therebetween.

The means for displacing the sealing element may be mounted on or in or may form part of the hollow connecting member connecting the two containers together.

Preferably, the hollow connecting member (when present) comprises the means for displacing the one or more sealing elements. The means for displacing the one or more sealing elements may comprise a cutting edge.

In one embodiment, the means for displacing the one or more sealing elements is actuable by relative rotational movement between the first and second containers.

For example, simple twisting of one container relative to the other could actuate the displacing means.

In another embodiment, the means for displacing the one or more sealing elements may be actuable by relative axial movement between the first and second containers. Typically, the relative axial movement comprises movement of the two containers towards each other. For example, simply pushing the two containers together could actuate the displacing means. In this case, in order to prevent unintended actuation of the displacing means, an initial resistance to movement of the containers can be provided and/or a locking mechanism can be provided that must be released before the two containers can be pushed together.

The initial resistance could be provided by a frangible or rupturable element which must be broken or ruptured before the containers can be pushed together.

Preferably, the relative movement is movement of the two containers towards one another.

Preferably, the hollow connecting member (when present) comprises the means for displacing the one or more sealing elements. The means for displacing the one or more sealing elements may comprise a cutting edge. The means for displacing the one or more sealing elements is actuable by relative movement between the first and second containers.

In one currently preferred embodiment, the means for displacing the one or more sealing elements is actuable by a combination of relative rotational movement and relative axial movement between the first and second containers. Such movement can be provided by means of a threaded connection between the two containers or between at least one of the containers and the hollow connecting member, when present.

The first container contains a pharmaceutical composition in a dispersible solid form. The dispersible solid form may be, for example, selected from a powder, granules, pellets or a tablet (i.e. a rapidly disintegrating tablet).

In one preferred embodiment, the dispersible solid form is a powder or granules, and most preferably a powder.

The pharmaceutical composition may contain a drug substance and optionally one or more pharmaceutical excipients. The drug substance may be, for example, an antibiotic such as a penicillin. Examples of penicillins include benzylpenicillin (penicillin G), phenoxymethylpenicillin (penicillin V or penicillin VK), nafcillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin, ampicillin, amoxicillin, bacampacillin, carbenicillin indanyl, ticarcillin, mezlocillin and piperacillin. Preferred penicillins are flucloxacillin, phenoxymethylpenicillin and amoxicillin.

The liquid diluent is typically aqueous. It may for example contain water and another liquid diluent such as ethanol but typically it contains water as the only liquid component.

In one embodiment, the liquid diluent is substantially pure water.

Preferably the liquid diluent is sterile water.

In one embodiment, the pharmaceutical composition and liquid diluent are selected such that when mixed and shaken, they form a pharmaceutical suspension.

In another embodiment, the pharmaceutical composition and liquid diluent are selected such that when mixed and shaken, they form a pharmaceutical solution.

Once the sealing elements have been displaced and the contents of the first and second containers have been mixed, the two containers may be separated. A cap (e.g. a screw cap) may then be placed over the container (e.g. the first container) containing the mixture of pharmaceutical composition and liquid diluents before presenting to the patient. Where the formulation is intended for administration to a child or other patient incapable of self administering the formulation, an oral syringe may be provided as part of the pharmaceutical package. The oral syringe may be provided separately or may form part of the cap Accordingly, in another embodiment, the invention provides a pharmaceutical package as hereinbefore defined further comprising a cap for removably closing one container to seal in the mixed pharmaceutical composition and liquid diluent after the said one container has been detached from the other container.

Both the cap and the oral syringe (when present) will typically be sterile and may be contained within sterile packaging prior to use.

Further embodiments and aspects of the invention will be apparent from the following description of a specific embodiment and the claims appended hereto.

Brief Description of the Drawings

Figure 1 is a side sectional elevation of a pharmaceutical package according to a first embodiment of the invention.

Figure 2 is a side sectional elevation corresponding to Figure 1 but showing the removal of security strips from the package.

Figure 3 is a side sectional elevation corresponding to Figures 1 and 2 but illustrates the package after displacement of the sealing elements and mixing of the contents of the two containers.

Detailed Description of the Invention

The invention will now be illustrated, but not limited, by reference to the specific embodiment shown in the accompanying drawings Figures 1 to 3.

As shown in Figure 1, a pharmaceutical package according to one embodiment of the invention comprises a first container (4) and a second container (2) connected by a hollow connecting member (14) so that the mouths of the two containers face one another. The two containers, which are typically formed from a pharmaceutical grade of polyethylene, each have a main body portion and a neck (12,10). The external surfaces of the necks (12) and (10) of the first and second containers are threaded and engage threads on the inner surface of the hollow connecting member (14). Each container has a sealing element in the form of a membrane (9, 7) across the neck so that the contents (not shown) of the interiors (8, 6) of the containers are kept separate from one another and are maintained in a sealed sterile condition. The sealing membranes are typically formed from aluminium/heat seal lacquer laminate. The interior of the hollow connecting member is also sterile.

The inner surface of the hollow connecting member 14 has two threaded regions that engage the threads on the outer surfaces of the necks of the two containers.

Between the two threaded regions is an inwardly oriented annular flange 20.

Extending from the radially inner edge of the annular flange 20 is a part-annular displacing member 22 which has cutting edges 22 and 24.

Security rings (16) and (18) are located between the shoulders of the two bottles and the two ends of the hollow connecting member 14. The security rings provide a visual indication that the package has not been opened and also help prevent accidental displacement of the sealing elements and premature mixing of the contents of the first and second containers.

The first container contains a pharmaceutical composition in dispersible solid form.

It may, for example, be a finely divided form such as a powder or granules.

The pharmaceutical composition typically contains one or more drug substances.

Alternatively, it may contain non-drug materials such as an oral rehydration composition.

Examples of pharmaceutical compositions are those containing drug substances that form suspensions in aqueous media. Particular examples of pharmaceutical compositions are those containing antibiotics and in particular penicillin antibiotics such as phenoxymethylpenicillin, amoxicillin and flucloxacillin.

The second container 2 contains a liquid diluent, and in particular an aqueous liquid diluent. The liquid diluent may be, for example, sterile water.

The pharmaceutical package illustrated in Figure 1 is delivered to the point (e.g. a pharmacy or a field location such as a field hospital) at which it is desired to dispense a liquid pharmaceutical formulation.

In order to prepare a liquid formulation such as a liquid suspension of a penicillin, the two security rings (16) and (18) are removed, as shown in Figure 2, and the two containers are rotated in opposite directions so that the necks of the containers screw further into the hollow connecting member (14). As the necks of the containers are screwed into the connecting member, the edges (24) and (26) on the displacing member (22) cut into the sealing membranes (7) and (9) around part of their circumference and push them aside, allowing the liquid diluent (e.g. sterile water) in the uppermost second container (2) to pour into the lowermost first container (4). The hollow connecting member (14) is then unscrewed from the first container (4) and a sterile screw cap (not shown) is placed over the neck of the first container. The container may then be shaken to create a liquid suspension or solution of the pharmaceutical composition ready for use by a patient.

The pharmaceutical packages of the invention may be used in pharmacies to simplify the preparation and dispensing of liquid formulations such as suspensions.

By using the package of the invention, there is no need for the dispensing pharmacist or a technician to weigh out or measure the components of the formulation and therefore potentially dangerous formulation errors can be avoided.

The pharmaceutical packages of the invention are also useful in field hospital situations (such as natural disasters) where supplies of sterile water may be impossible to obtain. The manner of construction of the packages means that a liquid formulation such as a suspension can be created quickly and simply on demand and without loss of sterility.

Equivalents It will readily be apparent that numerous modifications and alterations may be made to the specific embodiments of the invention described above without departing from the principles underlying the invention. All such modifications and alterations are intended to be embraced by this application.

Claims

CLAIMS1. A pharmaceutical package comprising first and second containers each having a mouth and an interior, the first and second containers being detachably connected together so that the mouths of the containers face one another: the interior of the first container having present therein a pharmaceutical composition in a dispersible solid form; the interior of the second container having present therein a liquid diluent; one or more sealing elements being positioned between the interior of the first container and the interior of the second container so as to prevent premature mixing of the pharmaceutical composition and the liquid diluents; wherein the package comprises means for displacing the one or more sealing elements so as to allow dispersion and mixing of the pharmaceutical composition and the liquid diluent; and wherein the means for displacing the one or more sealing elements is actuable by relative movement between the first and second containers.
2. A pharmaceutical package according to claim 1 wherein the means for displacing the one or more sealing elements is actuable by relative rotational movement between the first and second containers.
3. A pharmaceutical package according to claim 1 wherein the means for displacing the one or more sealing elements is actuable by relative axial movement between the first and second containers.
4. A pharmaceutical package according to claim 1 wherein the means for displacing the one or more sealing elements is actuable by a combination of relative rotational movement and relative axial movement between the first and second containers.
5. A pharmaceutical package according to any one of the preceding claims wherein the mouth of at least one of the containers is sealed by a said sealing element.
6. A pharmaceutical package according to claim 5 wherein the mouths of both containers are sealed by sealing elements.
7. A pharmaceutical package according to claim 5 or claim 6 wherein each sealing element is a membrane sealing the mouth of the container.
8. A pharmaceutical package according to any one of the preceding claims wherein the means for displacing the one or more sealing elements comprises a cutting member which cuts through at least part of the sealing element when the two containers are subjected to relative movement therebetween.
9. A pharmaceutical package according to any one of the preceding claims wherein the two containers are connected by means of a hollow connecting member.
10. A pharmaceutical package according to claim 9 wherein at least one of the containers has a threaded neck which engages a thread at one end of the hollow connecting member.
11. A pharmaceutical package according to claim 10 wherein both containers have threaded necks which engage threads at two opposed ends of the hollow connecting member.
12. A pharmaceutical package according to claim 10 or claim 11 wherein the hollow connecting member comprises the means for displacing the one or more sealing elements.
13. A pharmaceutical package according to claim 12 wherein the means for displacing the one or more sealing elements comprises one or more cutting or piercing formations.
14. A pharmaceutical package according to claim 13 wherein the means for displacing the one or more sealing elements comprises a cutting edge.
15. A pharmaceutical package according to claim 14 wherein the cutting edge is positioned so as to cut through and displace a said sealing element when a container is screwed onto the hollow connecting member.
16. A pharmaceutical package according to any one of the preceding claims wherein the pharmaceutical composition in a dispersible solid form is a powder.
17. A pharmaceutical package according to any one of the preceding claims wherein the pharmaceutical composition contains a drug substance and optionally one or more pharmaceutical excipients.
18. A pharmaceutical package according to claim 17 wherein the drug substance is an antibiotic.
19. A pharmaceutical package according to wherein the antibiotic is a penicillin.
20. A pharmaceutical package according to any one of the preceding claims wherein the liquid diluent is aqueous.
21. A pharmaceutical package according to any one of the preceding claims wherein the liquid diluent is sterile water.
22. A pharmaceutical package according to any one of the preceding claims wherein the pharmaceutical composition and liquid diluent are selected such that when mixed and shaken, they form a pharmaceutical suspension.
23. A pharmaceutical package according to any one of claims 1 to 21 wherein the pharmaceutical composition and liquid diluent are selected such that when mixed and shaken, they form a pharmaceutical solution.
24. A pharmaceutical package according to any one of the preceding claims further comprising a cap for removably closing one container to seal in the mixed pharmaceutical composition and liquid diluent after the said one container has been detached from the other container.