Title:
Container for constituting a formulation in liquid form
Kind Code:
A1


Abstract:
A container (70) for constituting a formulation in liquid form, comprises an elongate outer body (71) split into a first section (72) and a second section (73), along the longitudinal axis thereof, The container (70) has an inner chamber (77) divided into a first compartment (78) and a second compartment (79) by a seal (80). Seal (80) is movable in use between a closed position, wherein the first compartment 78 and the second compartment are sealed thereby, to an open position, wherein the first compartment (78) and the second compartment (79) are unsealed and any contents therein are free to mix together in the inner chamber (77) to form the formulation. The seal (80) is movable from the closed position to the open position by rotation of the first section (72) relative to the second section (73), and the volume of the inner chamber (77) remains unchanged following unsealing. Once the seal (80) has been moved to the open position it is retained in that position. Reversal of the rotational movement causes an outer cover (74) to become detached from a tear strip (75), permitting the outer cover (74) to be removed and the formulation to be capable of being delivered from the container (70). A formulation administered from the container (70) can ensure, for example, that a precise dose of an active ingredient is delivered to a patient, where the formulation is a pharmaceutical product.



Inventors:
Macken, Michael Joseph (Athlone, IE)
O'mara, Brendan Joseph (Meelick, IE)
Application Number:
11/547709
Publication Date:
08/23/2007
Filing Date:
04/07/2005
Assignee:
IDD-EAL MANUFACTURING COMPANY LIMITED (Athlone, County Roscommon, IE)
IDD-EAL PATENT HOLDING COMPANY LIMITED (Athlone, County Roscommon, IE)
Primary Class:
International Classes:
B65D25/08; A61J1/00; A61J1/20; B65D81/32
View Patent Images:
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Primary Examiner:
REYNOLDS, STEVEN ALAN
Attorney, Agent or Firm:
BIRCH, STEWART, KOLASCH & BIRCH, LLP (FALLS CHURCH, VA, US)
Claims:
1. A container for constituting a formulation in liquid form, which container comprises an elongate outer body split into sections along the longitudinal axis thereof, an inner chamber divided into a first compartment and one or more further compartments, a seal movable, in use, from a closed position, wherein all the compartments are sealed thereby, to an open position, wherein all the compartments are unsealed and any contents therein are free to mix together in the inner chamber to form the formulation, the seal being movable from the closed position to the open position by rotation, about the longitudinal axis of the elongate outer body, of one section thereof relative to another section thereof, such that the volume of the inner chamber remains unchanged following unsealing of the compartments, means for retaining the seal in the open position, an annular tear strip, which holds one section of the outer body in position over the first compartment, the outer body section, overlying the first compartment, and the annular tear strip being rotatable in one direction, which rotation causes displacement of the seal, and such that an attempt to rotate the outer body section, overlying the first compartment, in the opposite direction, in use, will cause the outer body section to tear away from the tear strip, allowing removal of the outer body section from the container.

2. A container according to claim 2, wherein the outer body is generally cylindrical in shape and is split into two generally cylindrical sections, the sections being butt-joined together to permit relative movement therebetween.

3. A container according to claim 2, wherein the two sections are joined together by a snap-fit.

4. A container according to claim 2, wherein the seal is a circular partition and is attached by a threaded section at the periphery thereof, in the closed position, to an inner threaded surface of one of the sections, such that the rotation of the one section relative to the other section unscrews the seal off the threaded surface from the closed position to the open position.

5. A container according to claim 1, wherein the seal is mounted at one end of an elongate connecting member, which elongate connecting member is locatable within the first compartment of the inner chamber, the end of the elongate member remote from the seal having formations thereon, which are engageable with complementary formations on an internal surface of the an outer body section overlying the compartment.

6. A container according to claim 5, wherein the outer body is generally cylindrical in shape and is split into two generally cylindrical sections, the first section having an opening at one end thereof, the opening being sealed, in storage, by the second section, which is in the form of a threaded closure, and wherein the seal is moved to the open position, in use, by an unsealing movement of the closure.

7. A container according to claim 6, wherein the opening is in a neck-shaped portion of the first section, the neck-shaped portion having a thread on the external surface thereof for engaging the closure and a thread on the inner surface thereof, the inner thread cooperating with a threaded section at the other end of the elongate connecting member, such that the unsealing movement of the closure results in the unscrewing of the elongate member from the neck-shaped portion and consequent movement of the seal to the open position.

8. A container according to claim 5, wherein the first compartment of the inner chamber in which the inner elongate connecting member is locatable is generally cylindrical in shape with an opening at each end thereof, with one opening being adapted to seat the seal in the closed position and the other end accommodating the end of the elongate member remote from the seal together with the complementary formations on the internal surface of the outer body section overlying the first compartment.

9. A container according to claim 8, wherein the first compartment is connected, at the end in which the seal is locatable, to a further outer body section, which further outer body section has one or more further internal compartments located therein.

10. A container according to claim 9, wherein, when the further outer body section has only one compartment located therein, the seal is movable into that compartment to the open position.

11. A container according to claim 10, wherein, in use, rotation of the outer body section, overlying the first compartment, results in a corresponding rotation of the first compartment relative to the further outer body section, and wherein sloping edges on the end of the elongate body remote from the seal move along corresponding sloping extensions on the inner surface of the first compartment causing the elongate body to be displaced along the longitudinal axis of the container to move the seal to the open position.

12. A container according to claim 10, wherein the formations on the elongate member are irreversibly disengaged from the complementary formations on the outer body section, overlying the first compartment, in the open position.

13. A container according to claim 9, wherein, when the further outer body section has more than one compartment located therein, the seal is movable away from those compartments to the open position.

14. A container according to claim 1, wherein one compartment is suitable for holding a quantity of liquid and the or each other compartment is suitable for holding a quantity of active ingredient.

15. A container according to claim 14, wherein the liquid is an aqueous medium.

16. A container according to claim 14, wherein the active ingredient is soluble in water.

17. A container according to claim 14, wherein the active ingredient is insoluble in water.

18. A container according to claim 14, wherein the active ingredient is in powder form.

19. A container according to claim 18, wherein the powder particles are micronised.

20. A container according to claim 18, wherein the particles are nanonised.

21. A container according to claim 14, wherein the one compartment can also hold an active ingredient prior to mixing.

22. A container according to claim 14, wherein the formulation is for delivery to a human or non-human animal.

23. A container according to claim 22, wherein the formulation is suitable for oral delivery.

24. A container according to claim 14, wherein the active ingredient is selected from an aquaceutical, nutriceutical, pharmaceutical, alcoholic beverage, non-alcoholic beverage, foodstuff, homeopathic agent, prebiotic, probiotic, or a mixture thereof.

25. A container according to claim 24, wherein the active ingredient is a probiotic which can provide up to 100% active probiotic agent after storage in dry form for up to 3 years.

26. A container according to claim 24, wherein the probiotic is a strain of probiotic bacterium selected from Lactobacillus Bifidobacterium, Streptococcus faecium and thermophilus, Entercoccus and Bacillus coagulans.

27. A container according to claim 24, which includes a prebiotic.

28. A container according claim 26, wherein the prebiotic is selected from saccharide materials including monosaccharides, disaccharides, oligosaccharides and/or polysaccharides wherein the monomeric units are selected from fructose, galactose, glucose and maltose, inulin-based prebiotic materials, garlic and extracts thereof, honey and extracts thereof and dietary fibre.

29. A container according to claim 24, wherein the formulation is free of lipid material.

30. A container according to claim 18, wherein the powder particles are in the form of particles which permit controlled release of the active ingredient therefrom in the gastrointestinal tract.

31. A container according to claim 30, wherein the particles have different release profiles.

32. A container according to claim 30, wherein the particles are coated with one or more polymeric materials so as to achieve said release.

33. A container according to claim 30, wherein the particles include a proportion of particles which allow for rapid release of the active ingredient on imbibtion of the formulation.

34. A container according to claim 24, wherein the formulation contains one or more excipients selected from absorption enhancers, acidity regulators, anti-oxidants, effervescing agents, flavourings, melt inhibiting agents, pH controlling agents, preservatives, solubility enhancers, sweeteners and taste-masking agents.

35. A container according to claim 24, wherein the active ingredient is a pharmaceutical selected from adrenergic agonists, adrenergic blockers, adrenocorticoids, agents for smoking cessation, anabolics, analgesics, androgens, antacids, antiallergy agents, anti-asthma agents, antibiotics, anti-cancer agents, anti-depressants, antidiabetic agents, anti-diarrheal agents, antiemetics, anti-epileptic agents, anti-gout agents, anti-hypertensives, antiinfectants, antimigraine agents, anti-obesity agents, anxiolytics, bronchodilators, contraceptives, cytokines, dietary supplements, gastrointestinal agents, hormones, laxatives, local anaesthetics, lymphokines, mucolytic agents, non-steroidal anti-inflammatory agents, steroids, vaccines and vitamins.

36. A container according to claim 24, wherein the formulation is adapted for topical delivery.

37. A container according to claim 36, which is used to deliver a hair dye.

38. A container according to claim 36, which is used to deliver a formulation to the vagina.

39. A container according to claim 38, wherein the formulation is in the form of a douche.

40. A container according to claim 38, wherein the active ingredient is a probiotic.

41. A container according to claim 40, which includes a prebiotic.

42. A container according to claim 1, wherein the volume of the liquid formulation is up to 5000 ml.

43. A container according to claim 1, wherein the container is used to constitute an air freshener.

44. A container according to claim 1, which is used to constitute a fuel.

45. A container according to claim 44, wherein the respective constituents are petrol and an oil.

46. A container according to claim 45, wherein the petrol and the oil are in the ratio of 40:1 for use in a two-stroke engine.

47. A container according to claim 14, wherein the liquid and the or each active ingredient are constituents used to form an adhesive or glue.

48. A container according to claim 1 for constituting a formulation in liquid form, substantially as hereinbefore described with particular reference to and as illustrated in FIGS. 1-3, FIGS. 4-6, FIGS. 7-10, and FIGS. 11-13 of the accompanying drawings.

49. 49-50. (canceled)

Description:

TECHNICAL FIELD

This invention relates to liquid formulations which are formed of constituents which are constituted prior to use because, for example, the constituents do not have the requisite activity or stability if stored in constituted form.

In one aspect the invention relates to pharmaceutical formulations for oral administration and, in particular, pharmaceutical formulations which can be imbibed directly from a container in which they are sold.

BACKGROUND ART

Medicines for oral administration are typically in capsule, granule, powder, tablet or other solid dosage unit form which are not readily swallowed without a drink of water or beverage.

In the case of medicines administered as liquids, syrups and the like, a spoon or other means of delivering the required amount of medicine to the mouth must be used and, indeed, must be to hand.

Elderly patients or individuals with special needs and children frequently experience problems in taking medication. For example, such persons may be reluctant to swallow or have difficulty in swallowing conventional oral dosage forms.

Those caring for the elderly, in particular health professionals, are legally prohibited from tampering with medication and are obliged to administer it in accordance with the manufacturer's instructions. However, for the reasons indicated above, such health professionals may be obliged to modify medication, for example, by breaking or crushing tablets, with the attendant legal consequences, in order to ensure that their patients receive their prescribed medication in an amount to ensure effective therapy.

Another problem with conventional medication is that it generally has an unpleasant taste. Although coatings, such as sugar coatings, can be applied to mask the taste of the active ingredient(s) or excipient(s), elderly and other patients often chew such medication exposing the unpleasant active agent or excipient which can result in medication being expelled from the mouth and thus the required dose is not received by the patient.

In many countries in the World it is difficult to find a clean water supply. Accordingly, if medication must be taken with a liquid, frequently the person taking the medication will need water in order to swallow the medication or, indeed, to solubilise the medication.

Also in the case of natural disasters such as earthquakes and floods, water supplies can be temporarily interrupted and again there is a need for medication which does not require one to have a clean water supply to hand.

A system has been proposed wherein an active ingredient in powder form is housed in a closure mechanism of a container for storage purposes and is released into a liquid medium in the container when it is desired to consume the active ingredient in liquid form. However, a problem that arises with such a system is that the active ingredient tends to cake in the closure, such that the full complement of active ingredient is not released into the liquid when required, with the attendant consequence of inadequate dosing.

Pharmaceutical formulations of the above type are just one example of formulations which require constitution prior to the point of use. However, there are many other types of formulations in the beverage, food, domestic and other sectors where one requires to use a formulation in a liquid state, but where the constituent parts thereof must remain unmixed until required for use as indicated above.

A formulation for feeding to a baby is an example of one of these other types of formulations. A number of containers are known in which components of such a formulation can be stored for subsequent mixing together when required.

For example, U.S. Pat. No. 5,419,445 describes a baby bottle with two compartments for storage of powdered baby formula and water. The water is stored in a bottle portion and the powdered formula is stored in a cartridge assembly. A nipple assembly is located at one end of the cartridge assembly, the other end of which cartridge assembly is located in the bottle portion. A seal is located between the cartridge assembly and the bottle portion, and this seal can be released by rotation of the nipple assembly. This activation of the mixing procedure, by rotation of the nipple assembly, causes the seal to be unscrewed from the cartridge assembly resulting in the release of the powdered formula and the seal into the water. The released seal acts as a means for mixing the powder and water while the bottle is shaken.

The rotation of the nipple assembly during activation causes the separate internal compartments to merge together resulting in a smaller container. Thus, this feature limits the amount of storage space available in the pre-activated bottle.

Such a bottle could be used for the constitution of formulations other than baby feeds. However, the fact that the seal is released into the bottle on activation could cause problems with more viscous formulations as the seal might block the space between the two compartments resulting in incomplete mixing of the formulation.

It is an object of the present invention to overcome the problems of containers of the type hereinbefore described.

DISCLOSURE OF INVENTION

Accordingly, the invention provides a container for constituting a formulation in liquid form, which container comprises an elongate outer body split into sections along the longitudinal axis thereof, an inner chamber divided into two or more compartments, a seal movable, in use, from a closed position, wherein all the compartments are sealed thereby, to an open position, wherein all the compartments are unsealed and any contents therein are free to mix together in the inner chamber to form the formulation, the seal being movable from the closed position to the open position by rotation of one section of the outer body relative to another section thereof, such that the volume of the inner chamber remains unchanged following unsealing of the compartments, and means for retaining the seal in the open position.

An advantage of having a container with a seal which is retainable in the open position is that, following unsealing, mixing of the contents in the inner chamber cannot be impeded by the seal. If, following unsealing, the seal were free to move about within the inner chamber, it might partially or totally block transfer of the contents of the inner chamber between the compartments.

The avoidance of the potentially blocking action of a released seal means that the thorough mixing of the contents of the inner chamber can take place and that the mixed contents can be delivered from the container when required.

The volume of the inner chamber of the container according to the invention remains unchanged following unsealing of the compartments, and this has the advantage that this volume is available for mixing of the contents of the container.

The container according to the invention can be used to maintain the constituents of a liquid formulation in an active or stable form until they are required for use, thereby extending their shelf life, while at the same time providing a convenient and practicable means of dispensing the formulation at the point of use.

The invention will principally be illustrated herein with reference to a pharmaceutical or other liquid formulation in a ready-to-drink form, hereinafter to referred to collectively and for convenience as a pharmaceutical formulation.

Thus, a ready-to-drink pharmaceutical formulation administered from a container according to the invention overcomes the problem of conventional oral dosage forms mentioned above, as well as the problem of inadequate or failed release of an active ingredient from a closure mechanism of the type hereinabove described.

The container allows for a ‘one shot’ administration of a required dose of pharmaceutical formulation to a subject. Also because of the form of the active ingredient in the formulation, the formulation can result in immediate uptake or delayed onset of action of the active ingredient, because the formulation comes into immediate contact with the mouth and upper parts of the gastrointestinal tract. Thus, absorption can commence sublingually, through the walls of the buccal cavity, in the throat and oesophagus, rather than commencing in the stomach. A formulation administered from a container according to the invention can ensure that a precise dose of an active ingredient is delivered to a subject.

According to a first embodiment of the invention, the outer body is generally cylindrical in shape and is split into two generally cylindrical sections, the sections being butt-joined together to permit relative movement therebetween.

By butt-joined herein is meant that the two sections are joined in such a way that they are connected together at opposing ends of the cylinders and that the rotational movement is between these two butt-joined cylindrical sections.

Preferably, the two sections are joined together by a snap-fit.

Further, preferably, the seal is a circular partition and is attached by a threaded section at the periphery thereof, in the closed position, to an inner threaded surface of one of the sections, such that the rotation of the one section relative to the other section unscrews the seal off the threaded surface from the closed position to the open position.

However, it will be appreciated that the container according to the invention can have a wide variety of shapes depending on the use to which it is to be put. Furthermore, the container can have aesthetic features or features which would appeal to a particular group of users, such as children.

According to a second embodiment of the invention, the seal is mounted at one end of an elongate connecting member, which elongate connecting member is locatable within a first compartment of the inner chamber, the end of the elongate member remote from the seal having formations thereon, which are engageable with complementary formations on an internal surface of an outer body section overlying the compartment.

Preferably, the outer body is generally cylindrical in shape and is split into two generally cylindrical sections, the first section having an opening at one end thereof, the opening being sealed, in storage, by the second section, which is in the form of a threaded closure, and wherein the seal is moved to the open position, in use, by an unsealing movement of the closure.

This arrangement is advantageous in that the unsealing movement does not require much strength on the part of the user, as it only requires that the closure be turned.

Further, preferably, the opening is in a neck-shaped portion of the first section, the neck-shaped portion having a thread on the external surface thereof for engaging the closure and a thread on the inner surface thereof, the inner thread cooperating with a threaded section at the other end of the elongate connecting member, such that the unsealing movement of the closure results in the unscrewing of the elongate member from the neck-shaped portion and consequent movement of the seal to the open position.

According to a third embodiment of the invention, the first compartment of the inner chamber in which the inner elongate connecting member is locatable is generally cylindrical in shape with an opening at each end thereof, with one opening being adapted to seat the seal in the closed position and the other end accommodating the end of the elongate member remote from the seal together with the complementary formations on the internal surface of the outer body section overlying the first compartment.

One advantage of this arrangement is that the outer body can be rotated and consequently the seal moved to the open position by gripping the outer body at any convenient position thereon. This rotational movement of the outer body is translated through the formations on the elongate member and the complementary formations on the outer body to provide the unsealing movement of the seal.

A further advantage of this arrangement is that it allows the outer cover to be gripped by the user in order to turn it relative to the inner compartment so as to unseal the inner compartment and permit mixing of an active ingredient and a quantity of fluid, while at the same time avoiding any risk of the fluid escaping prematurely frdm the container.

Preferably, the outer body section is held in position over the inner compartment by an annular tear strip.

Further, preferably, the outer body section and the annular tear strip are rotatable in one direction, which rotation causes displacement of the seal, and wherein an attempt to rotate the outer body section in the opposite direction causes the outer cover to tear away from the tear strip allowing removal of the outer body section from the container.

This arrangement allows the user to remove the outer cover from the container following mixing of the contents.

Suitably, the first compartment is connected, at the end in which the seal is locatable, to a further outer body section, which further outer body section has one or more further internal compartments located therein.

Preferably, when the further outer body section has only one compartment located therein, the seal is movable into that compartment to the open position.

Further, preferably, in use, rotation of the outer body section results in a corresponding rotation of the first compartment relative to the further outer body section, and sloping edges on the end of the elongate body remote from the seal move along corresponding sloping extensions on the inner surface of the first compartment causing the elongate body to be displaced along the longitudinal axis of the container to move the seal to the open position.

Suitably, the formations on the elongate member are irreversibly disengaged from the complementary formations on the outer body section in the open position.

According to a fourth embodiment of the invention, when the further outer body section has more than one compartment located therein, the seal is movable away from those compartments to the open position.

An advantage of this container is that active ingredients which would be subject to loss of activity if mixed together can be kept apart from one another until the time comes to constitute the formulation.

Preferably, one compartment is suitable for holding a quantity of liquid and the or each other compartment is suitable for holding a quantity of active ingredient.

The active ingredient can be in a dry form prior to mixing or already in a liquid form, as required, as hereinafter described.

The liquid can be any liquid as the intended use requires, for example a range of solvents or organic chemicals. For those formulations which are to be consumed or imbibed in use, the liquid will generally be an aqueous or aqueous-based medium.

Thus, in one embodiment, the liquid is an aqueous medium.

The aqueous medium can be or consist substantially of water.

The active ingredient can include a mixture of active ingredients, if required.

The liquid formulation once formed can include the active ingredient in solution or as a dispersion thereof.

According to one embodiment, the active ihgredient is soluble in water.

According to an alternative embodiment, the active ingredient is insoluble in water.

The container must generally be shaken or otherwise agitated in order to disperse the active ingredient in the aqueous medium especially prior to consumption, in particular in the case of insoluble active ingredients.

As indicated above, the container can have a variety of forms or shapes, including bottles, cans, cartons, jars, pouches, sachets or tubs.

For example, a suitable type of pouch is a foil pouch of the type sold under the Trade Mark GUALA.

For ready-to-drink formulations, the container will suitably contain a volume in the range 40-100 ml, but typically the final volume of a pharmaceutical formulation will not be greater than 100 ml, so as to ensure that the intended dose of active ingredient is taken.

However, for other uses the volume of the container will be considerably greater as hereinafter described.

A range of materials can be used in the manufacture of the container according to the invention. However, typically the container will be made of plastics materials, more especially thermoplastics materials such as high density polyethylene (HDPE), polyethylene (PE), low density polyethylene (LDPE) or polyethylene terephthalate (PET), especially for aqueous or aqueous-based liquids.

However, as the container can also be used for the constitution of materials which include organic solvents and petroleum products, other plastics materials may be used which are resistant or inert to the materials contained therein.

Furthermore, where the container is a can, the material used to form the can may be aluminium, tin, steel or a plastics material as hereinbefore described.

Preferably, the container will be fitted with a conventional tamper-evident closure to ensure users that the container has not been opened or tampered with since leaving the factory or site of manufacture or prior to administration or use.

It will normally be necessary to supply the container in accordance with the invention with a child-proof closure, because of the nature of the active ingredients, although normal parental control and, indeed, consumer awareness will be assumed in the use of the formulations to be administered from a container according to the invention.

The active ingredient is maintained in unconstituted form in spaced-apart relationship from the aqueous medium in the container until the formulation is ready to be used.

Thus, by unconstituted herein is meant that the aqueous liquid and the active ingredient, in whatever form, are maintained in the state in which they were introduced into the container, until such time as the seal is moved to the open position, thus initiating the constitution of the formulation.

According, to one embodiment, the active ingredient is in powder form.

In one preferred embodiment, the powder particles are micronised.

In another preferred embodiment, the particles are nanonised.

In a further embodiment, the one compartment can also hold an active ingredient prior to mixing.

The formulation constituted by actuating the container according to the invention on unsealing the partition can be delivered to a human or non-human animal.

Thus, in one embodiment the formulation is suitable for oral delivery.

Thus, according to this aspect of the invention, the active ingredient is selected from an aquaceutical, nutriceutical, pharmaceutical, alcoholic beverage, non-alcoholic beverage, foodstuff, homeopathic agent, prebiotic, probiotic, or a mixture thereof.

For example, the active ingredient can be a probiotic which can provide up to 100% probiotic agent after storage in dry form for up to 3 years.

According to this embodiment the probiotic is a strain of a probiotic bacterium selected from Lactobacillus, Bifidobacterium, Streptococcus faecium and thermophulus, Enterococcus and Bacillus coagulans.

Examples of suitable probiotics are: Lactobacillus acidophilus, Lactobacillus caesi imunitass, Lactobacillus bulgaricus, Lactobacillus helveticus, Lactobacillus rhamnossus A, Lactobacillus salivarious, Lactobacillus reuteri, Lactobacillus casei, Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus rhamnossus B, Lactobacillus lactis: Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlactis, Bifidobacteriumlongum, Bifidobacterium breve; Streptococcus faecium, Streptococcus thermpophilius; Enterococcus and Bacillus coagulans.

Thus, the formulation can be a yogurt-type drink containing conventional probiotic products of the type mentioned above, which are generaily only suitable for storage under a refrigerated condition for a period of about 21 days. Frequently, such products contain only about 1% of their original activity at the time of consumption.

Especially preferred probiotics are those with anti-cholesterolaemic activity.

The container can also include a prebiotic in addition to the probiotic.

A prebiotic as used in accordance with the invention is generally a nutrient material that is not digestible in the small intestine and passes to the large intestine where it serves as a nutrient source for probiotic bacteria.

Examples of suitable prebiotics are selected from saccharide materials including monosaccharides, disaccharides, oligosaccharides and/or polysaccharides wherein the monomeric units are selected from fructose, galactose, glucose and maltose, inulin-based prebiotic materials, garlic and extracts thereof, honey and extracts thereof and dietary fibre.

Thus, suitable such materials are lactose, sucrose, dextrin, cellulose, glycogen and starch.

Many prebiotic materials of fruit or vegetable origin or plant origin generally are suitable for use as a prebiotic herein.

Thus, other suitable prebiotics include inulin-based prebiotics derived from chickory, Jerusalem artichoke or dandelion, garlic or garlic extracts. Another suitable prebiotic is honey or extracts thereof and dietary fibre generally.

According to a preferred embodiment of the invention, the formulation is free of lipid material.

Thus, the probiotic products delivered in accordance with the invention are lipid-free and thus not based on dairy products.

When the formulation to be delivered from the container in accordance with the invention is for oral delivery and the or each active ingredient is in the form of powder particles, especially when said active ingredient is a pharmaceutical or other agent having a therapeutic or prophylactic effect, said powder particles are in the form of particles which permit controlled release of the active ingredient therefrom in the gastrointestinal tract.

The active ingredient can typically be in capsule, granule, liquid, powder or tablet form.

When the active ingredient is in powder form, preferably the powder particles are in the form of particles which permit controlled release of the active ingredient therefrom in the gastrointestinal tract.

Further, preferably, the particles have different release profiles.

A wide variety of particles from which the active ingredient is released in a controlled and pre-determined manner in the gastrointestinal tract can be used in the formulation according to the invention and are known to those skilled in the art.

In order to ensure controlled release of the active ingredient, preferably the particles are coated with one or more polymeric materials so as to achieve said controlled release.

As indicated above, the particles can be micronised or of smaller size, namely nanosized, referred to herein as “nanonised”.

In one aspect of the invention, the active ingredient is in the form of a plurality of particles or multiparticulates, each particle comprising a core of the active ingredient or a pharmaceutically acceptable salt thereof surrounded by a polymeric coating effective to achieve the desired release profile.

A sealant or barrier layer can be applied to the core prior to the application of the polymeric coating.

Suitable sealants or barriers are permeable or soluble agents such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl ethylcellulose and xanthan gum.

Other agents can be added to improve the processability of the sealant or barrier layer. Such agents may include talc, colloidal silica, polyvinyl alcohol, titanium dioxide, micronised silica, fumed silica, glycerol monostearate, magnesium trisilicate or magnesium stearate or a mixture thereof.

The sealant or barrier layer can be applied from solution using methods known to those skilled in the art.

Suitably, the active ingredient is applied to an inert core such as non-pareil seeds having an average diameter in the range of 0.4-1.1 mm, more especially 0.85-1.00 mm.

The active ingredient can be applied with or without additional excipients onto the inert cores. The active ingredient can be sprayed from solution or suspension using for example a fluidised bed coater, or in a pan coating system. Alternatively, the active ingredient can be applied as a powder onto the inert cores using a binder to bind the active ingredient onto the cores. Cores can also be formed by extrusion of the core with suitable plasticisers as described below and any other processing aids as necessary.

A wide range of polymers can be used in the polymer coating. Examples of such polymers include polymer coating materials, such as cellulose acetate phthalate, cellulose acetate trimaletate, hydroxy propyl methylcellulose phthalate, polyvinyl acetate phthalate, Eudragit® poly acrylic acid and poly acrylate and methacrylate coatings such as Eudragit® S or Eudragit® L, polyvinyl acetaldiethylamino acetate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate trimellitate, shellac; hydrogels and gel-forming materials, such as carboxyvinyl polymers, sodium alginate, sodium carmellose, calcium carmellose, sodium carboxymethyl starch, polyvinyl alcohol, hydroxyethyl cellulose, methyl cellulose, gelatin, starch and cellulose based cross-linked polymers such as hydoxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, cross-linked starch, microcrystalline cellulose, chitin, cellulose acetate cellulose propionate, cellulose acetate propionate, cellulose acetate butyrate, cellulose triacetate, aminoacryl-methacrylate copolymer (Eudragit® RS-PM, Rohm & Haas), pullutan, collagen, casein, agar, gum arabic, sodium carboxymethyl cellulose, carboxymethyl ethyl cellulose, (swellable hydrophilic polymers) poly(hydroxyalkyl methacrylate) (m. wt. ˜5 k-5,000 k), polyvinylpyrrolidone (m. wt. ˜10 k-360 k), anionic and cationic hydrogels, polyvinyl alcohol having a low acetate residual, a swellable mixture of agar and carboxymethyl cellulose, copolymers of maleic anhydride and styrene, ethylene, propylene or isobutylene, pectin (m. wt. ˜30 k-300 k), polysaccharides such as agar, acacia, karaya, tragacanth, algins and guar, polyacrylamides, Polyox® polyethylene oxides (m. wt. ˜100 k-5,000 k), AquaKeep® acrylate polymers, diesters of polyglucan, cross-linked polyvinyl alcohol and poly N-vinyl-2-pyrrolidone, sodium starch glucolate (e.g. Explotab®; Edward Mandell C. Ltd.); hydrophilic polymers such as polysaccharides, methyl cellulose, calcium carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, nitrocellulose, carboxymethyl cellulose, cellulose ethers, poly(ethylene terphthalate), poly(vinyl isobutyl ether), polyurethane, polyethylene oxides (e.g. Polyox®, Union Carbide), methyl ethyl cellulose, ethylhydroxy ethylcellulose, cellulose acetate, ethylcellulose, cellulose butyrate, cellulose propionate, gelatin, collagen, starch, maltodextrin, pullulan, polyvinyl pyrrolidone, polyvinyl alcohol, polyvinyl acetate, glycerol fatty acid esters, polyacrylamide, polyacrylic acid, ammonio methacrylate copolymers such as Eudragit® RL or Eudragit® RS (e.g. Eudragit®, Rohm and Haas), other acrylic acid derivatives, sorbitan esters, polydimethyl siloxane, natural gums, lecithins, pectin, alginates, ammonia alginate, sodium, calcium, potassium alginates, propylene glycol alginate, agar, gums: arabic, karaya, locust beah, tragacanth, carrageenans, guar, xanthan, scleroglucan and mixtures and blends thereof.

In one embodiment, the polymeric coating contains a major proportion of a pharmaceutically acceptable film-forming polymer which forms an insoluble film of low permeability.

In another embodiment, the polymeric coating contains a minor proportion of a pharmaceutically acceptable film-forming polymer which forms an insoluble film of high permeability.

Further, preferably, the or each polymer is a methacrylic acid co-polymer.

Alternatively, the or each polymer is an ammonio methacrylate co-polymer.

However, a mixture of methacrylic acid co-polymers and ammonio methacrylate co-polymers can be used.

Methacrylic acid co-polymers which include polymers sold under the Trade Marks Eudragit S and Eudragit L by Rohm & Haas are suitable for use in the formulations according to the invention.

Ammonio methacrylate co-polymers which include polymers sold under the Trade Marks Eudragit RS and Eudragit RL by Rohm & Haas are also suitable for use in the formulations according to the invention.

The two types of polymers can also be combined in any ratio in separate coats on the cores.

In addition to the Eudragit polymers described above, a number of other such polymers can be used to create a lag in release. These include methacrylate ester co-polymers (e.g. Eudragit NE 30D).

Further information on the Eudragit polymers is to be found in Chemistry and Application Properties of Polymethacrylate Coating Systems” from “Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms” edited by James McGinity (Marcel Dekker Inc., New York) pg 109-114).

The polymeric coating can include one or more soluble excipients so as to increase the permeability of the coating.

Suitably, the or each soluble excipient when such is used is selected from a soluble polymer, a surfactant, an alkali metal salt, an organic acid, a sugar and a sugar alcohol.

Examples of soluble excipients include polyvinyl pyrrolidone, polyethylene glycol, sodium chloride, surfactants such as sodium lauryl sulphate and polysorbates, organic acids such as acetic acid, adipic acid, citric acid, fumaric acid, glutaric acid, malic acid, succinic acid, and tartaric acid and sugars such as dextrose, fructose, glucose, lactose and sucrose, and sugar alcohols such as lactitol, maltitol, mannitol, sorbitol and xylitol, xanthan gum, dextrins, poloxamers and maltodextrins,

The polymeric coating can also include one or more auxiliary agents selected from a filler, a plasticiser and an anti-foaming agent.

Representative fillers include talc, fumed silica, glyceryl monostearate, magnesium stearate, calcium stearate, kaolin, colloidal silica, gypsum, micronised silica and magnesium trisilicate.

The quantity of filler used can be up to about 300% by weight based on the total dry weight of the polymer.

The coatings can also include a material that improves the processing of the polymers. Such materials are generally referred to as “plasticisers” and include, for example, adipates, azelates, benzoates, citrates, isoebucates, phthalates, sebacates, stearates and glycols.

Representative plasticisers include acetylated monoglycerides; butyl phthalyl butyl glycolate; dibutyl tartrate; diethyl phthalate; dimethyl phthalate; ethyl phthalyl ethyl glycolate; glycerin; ethylene glycol, propylene glycol; triacetin citrate; triacetin; tripropinoin; diacetin; dibutyl phthalate; acetyl monoglyceride; polyethylene glycols; castor oil; triethyl citrate; polyhydric alcohols, acetate esters, gylcerol triacetate, acetyl triethyl citrate, dibenzyl phthalate, dihexyl phthalate, butyl octyl phthalate, diisononyl phthalate, butyl octyl phthalate, dioctyl azelate, epoxidised tallate, triisoctyl trimellitate, diethylhexyl phthalate, di-n-octyl phthalate, di-i-octyl phthalate, di-i-decyl phthalate, di-n-undecyl phthalate, di-n-tridecyl phthalate, tri-2-ethylhexyl trimellitate, di-2-ethylhexyl adipate, di-2-ethylhexyl sebacate, di-2-ethylhexyl azelate, dibutyl sebacate, glyceryl monocaprylate and glyceryl monocaprate.

The amount of plasticiser to be used in the coating can be from about 10% to 50% based on the weight of the dry polymer.

The amount of coating to be used in forming the multiparticulates will be determined by the desired delivery properties and release profiles, including the amount of drug to be delivered, the time delay desired, and the size of the multiparticulates.

A sealant or barrier layer may be applied to the polymeric coating.

The sealant or barrier layer, when such is present, can be formed of any of the materials hereinabove specified for the sealant or barrier layer applied to a core.

When the active ingredient is in the form of particles, then the particles can include a proportion of particles which allow for rapid release of the active ingredient on imbibtion of the formulation.

Formulation for oral delivery will generally contain one or more excipients selected from absorption enhancers, acidity regulators, anti-oxidants, effervescing agents, flavourings, melt inhibiting agents, pH controlling agents, preservatives, solubility enhancers, sweeteners and taste-masking agents.

Examples of such excipients are specified hereinbelow. However, other excipients known in the art can also clearly be used, where appropriate.

Such excipients can be selected so as to extend the shelf life of the product, a shelf life of thirty six months being possible.

Examples of suitable absorption enhancers include: acetone, alcohols, ascorbic acid, bile salts, chitosan, citric acid, cyclodextrins, dimethyl sulfoxide, isopropyl myristate, oleic acid, polidocanol (Laureth 9), polyethylene glycol, propylene glycol and sodium lauryl sulfate.

Examples of suitable acidity regulators include: fumaric acid, lactic acid, sodium phosphate (dibasic and monobasic) and tartaric acid.

Examples of suitable anti-dxidants include: alpha tocopherol, ascorbic acid, butylated hydroxyanisole, butylated hydroxytdluene, fumaric acid, malic acid, propyl gallate, sodium ascorbate, sodium metabisulfite, sodium sulfite and stearic acid.

Examples of suitable effervescing agents include: citric acid and sodium bicarbonate and/or potassium hydrogen bicarbonate. However, as indicated above other effervescing agents, known in the art can also be used.

Examples of suitable flavourings include fruit flavouring agents.

The flavouring agent, which may be any fruit flavour, such as apple, banana, blackberry, cranberry, orange, peach, raspberry or strawberry assists in masking any organoleptically unacceptable taste associated with the active ingredient or excipients.

Herbal and other flavourings can also be used, for example menthol, mint, peppermint or vanilla. A combination of such flavourings and fruit flavourings can also be used, for example orange and peach or orange and mint.

Examples of suitable pH controlling agents include: malic acid, potassium citrate, sodium citrate and sodium phosphate (dibasic and monobasic).

Examples of suitable preservatives include: dimethyldicarbonate, glycerol, methylparaben, potassium sorbate, propylparaben, sodium benzoate, sodium metabisulphite and sulphur dioxide, benzalkonium chloride, sodium propionate and sorbic acid.

Examples of suitable solubility enhancers include: alcohols, inorganic sdlvents, organic solvents, pH adjusting agents in the form of buffers, poloxamers and surfactants.

Suitable poloxamers are poloxamer polyols.

The poloxamer polyols are a series of closely related block copolymers of ethylene oxide and propylene oxide.

More specifically, the poloxamer polyols are α-hydro-ω-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene)block copolymers, more generally known as polyethylene-propylene glycol copolymer or polyoxyethylene-polyoxypropylene copolymer.

Preferred poloxamers are those which contain between 60% and 90%, more especially between 70% and 80%, by weight of the polyoxyethylene portion.

Examples of such poloxamers, are known by the trade names Lutrol, Monolan and Pluronic.

The poloxamer, when such is used, is melted and then the active ingredient and any auxiliary agents(s) are dispersed in the molten poloxamer.

By poloxamer herein is meant also a combination of two or more poloxamers.

Surfactants can include: anionic, cationic, natural and nonionic surfactants.

Examples of suitable sweeteners include: artificial and natural sweeteners. Artificial sweeteners used in accordance with the invention are preferably selected from aspartame and acesulfame potassium or a mixture thereof, although other artificial sweeteners, such as saccharin, can also be used. Natural sweeteners included fructose and sucrose.

Examples of suitable taste-masking agents include: acesulfame potassium, alginic acid, alpha glucans, aspartame, dextrose, ethyl maltol, ethyl vanillin, fumaric acid, fructose, glycerol, lactitol, malic acid, maltitol, maltol, maltose, menthol, pectin, saccharin, sorbitol, sucrose, starch and starch derivatives, tartaric acid and vanillin.

It will be appreciated that there is an overlap between the excipients used for different purposes.

Preferably, the liquid contains a preservative, although the liquid could also be pasteurised, if desired. The liquid can also contain other ingredients, such as a sweetener, if required.

When the container is made of a plastics material, if pasteurisation is to be used, the so-called flash or hot fill pasteurisation technique would be used.

Flash pasteurisation entails raising a liquid to over 65° C. for a very short period of time and then immediately lowering the temperature to approximately 30-40° C., just prior to filling. This method can be used with plastics bottles. However, with this method there is a risk that the liquid can be contaminated between the flash pasteurisation and the point of filling. Accordingly, typically this method of pasteurisation is used in conjunction with a preservative of the type hereinabove specified.

Hot fill pasteurisation, as the name suggests, involves raising the liquid to over 65° C. and maintaining this temperature while filling. Thus, this method can be conveniently used with both glass and special temperature resistant plastics bottles, for example PET.

A wide range of active ingredients or combination of active ingredients can be formulated in accordance with the invention. References herein to particular active ingredients include also pharmaceutically acceptable salts, bases, hydrates and other forms thereof.

By pharmaceutical in this context is also meant homeopathic agents and what are referred to as alternative medicines.

Suitable pharmaceuticals are selected from adrenergic agonists, adrenergic blockers, adrenocorticoids, agents for smoking cessation, anabolics, analgesics, androgens, antacids, antiallergy agents, anti-asthma agents, antibiotics, anti-cancer agents, anti-depressants, antidiabetic agents, anti-diarrheal agents, antidotes, antiemetics, anti-epileptic agents, anti-gout agents, antihistamines, anti-hypertensives, anti-hypercholesterolaemics, antiinfectants, antimigraine agents, anti-obesity agents, anti-osteoporosis agents, anxiolytics, blood modifiers, bronchodilators, cardiovascular agents, contraceptives, cytokines, dietary supplements, fertility agents, gastrointestinal agents, hormones, hypnotics, laxatives, local anaesthetics, lymphokines, minerals, mucolytic agents, narcotics, non-steroidal anti-inflammatory agents, psychotherapeutic agents, steroids, vaccines and vitamins.

Suitable adrenergic agonists or selective β2 agonists include: salbutamol and terbutaline.

Suitable adrenergic blockers or α/β blockers include: carvedilol, metoprolol and propranolol.

Suitable adrenocorticoids include: betamethasone; corticosterone; cortisone; fluocinolone; fluprednisolone; fluticasone propionate; hydrocortisone; methylprednisolone; mometasone; paramethasone; prednisolone; prednisone; and triamcinolone.

Suitable agents for smoking cessation include, in particular nicotine.

Suitable anabolics include: aldactazide and aldactone.

Suitable analgesics include: acetaminophen; acetylsalicylic acid (aspirin); alfentanil; benorylate; buprenorphine; butorphanol; choline magnesium trisalicylate; codeine; diamorphine hydrochloride; diflunisal; dihydrocodeine phosphate; fentanyl; hydrocodone; levorphanol; meptazinol hydrochloride; methadone hydrochloride; morphine; nalbuphine hydrochloride; nefopam hydrochloride; oxycodone hydrochloride; pentazocine; pethidine hydrochloride; phenacetin; phenazocine hydrobromide; phenazopyridine hydrochloride; phenoperidine hydrochloride; sodium salicylate; sufentanil citrate; and tramadol hydrochloride.

Suitable androgens include: testosterone; and danazol.

Suitable gastrointestinal agents, including antacids, anti-diarrheal agents and antiemetics and include: aluminium hydroxide; calcium carbonate; cimetidine; famotidine; lansoprazole; magnesium hydroxide; magnesium trisilicate; omeprazole; rabeprazole; ranitidine; sodium bicarbonate; loperamlde hydrochloride; diphenoxylate hydrochloride; zaldaride; diphenidol hydrochloride; domperidone; metoclopramide hydrochloride; and ondansetron hydrochloride.

Suitable anti-allergy agents include: astemizole; azatadine maleate; bromodiphenydramine hydrochloride; brompheniramine maleate; carbinoxamine maleate; cetirizine hydrochloride; chlorpheniramine maleate; clemastine fumarate; cyclizine; cyproheptadine hydrochloride; dimethindene maleate; diphenhydramine; diphenylpyraline hydrochloride; doxylamine succinate; fexofenadine hydrochloride; loratadine; mebhydrolin; pheniramine; phenyltoloxamine citrate; terfenadine; tripelennamine; and triprolidine hydrochloride.

Suitable anti-asthma agents and bronchodilators include aminophylline; clenbuterol hydrochloride; ketolifen; orciprenaline; salbutamol; terbutaline sulphate; theophylline; and beclomethasone.

Suitable antibiotics include: amoxycillin; ampicillin; azithromycin; bacampicillin hydrochloride; carbenicillin sodium; cefaclor; cefadroxil; cefuroxime; cephalexin; chloramphenicol; ciprofloxacin; clarithromycin; clindamycin hydrochloride; cloxacillin; erythromycin; lincomycin hydrochloride; metampicillin; mupirocin; neomycin; norfloxacin; ofloxacin; rifampicin; and ticarcillin sodium.

Suitable anti-cancer agents include: bleomycin sulphate; busulphan; carboplatin; chlorambucil; cisplatin; cyclophosphamide; mercaptopurine; melphalan; methotrexate; mitotane; procarbazine hydrochloride; and tamoxifen citrate.

Suitable anti-cholesterolaemic agents include: phytosterols; beta-sitosterol; campsterol; stigmasterol; brassicasterol; and situstanol.

Suitable anti-depressants include: amitriptyline; amoxapine; bupropion hydrochloride; desipramine; fluoxetine hydrochloride; fluvoxamine maleate; imipramine; lithium carbonate; maprotiline; mianserin hydrochloride; moclobemide; nomifensine maleate; paroxetine hydrochloride; sertraline hydrochloride; trazodone hydrochloride; trimipramine; and venlafaxine hydrochloride.

Suitable anti-diabetic agents include: acarbose; chlorpropamide; glimepiride; glipizide; insulin; metformin hydrochloride; tolazamide; tolbutamide; and troglitazone.

Suitable anti-epileptic agents include: carbamazepine; lamotrigine and phenytoin sodium.

Suitable anti-gout agents include: allopurinol; colchicine; and sulphinpyrazone.

Suitable anti-hypertensives include: acebutolol hydrochloride; alprenolol; amiloride; amlodipine besylate; atenolol; benzthiazide; betaxolol hydrochloride; bisoprolol fumarate; bupranolol hydrochloride; captopril; carvedilol; chlorothiazide; chlorthalidone; clonidine hydrochloride; diltiazem hydrochloride; doxazosin mesylate; enalapril; fosinopril sodium; guanabenz acetate; guanadrel sulphate; guanethidine monosulphate; guanfacine hydrochloride; hydrochlorothiazide; indapamide; isradipine; lisinopril; losartan potassium; mefruside; methyldopa; metolazone; metoprolol tartrate; moexipril hydrochloride; nadolol; nicardipine hydrochloride; nifedipine; oxprenolol; pindolol; polythiazide; prazosin hydrochloride; propranolol hydrochloride; quinapril hydrochloride; quinethazone; ramipril; terazosin hydrochloride; timolol maleate; triamterene; trichlormethiazide; valsartan; hydralazine hydrochloride; minoxidil; phentolamine mesylate; and terazosin hydrochloride.

Suitable anti-infectants include: domiphen bromide; aminosalicylic acid; cinoxacin; dapsone; dicloxacillin; hetacillin; isoniazid; lomefloxacin hydrochloride; loracarbef; nafcillin sodium; nalidixic acid; nitrofurantoin; oxacillin sodium; pyrazinamide; sulfacytine; sulphamethoxazole; tobramycin; trimethoprim; butoconazole nitrate; clotrimazole; fluconazole; griseofulvin; itraconazole; ketoconazole; miconazole; nystatin; terbinafme hydrochloride; terconzaole; tioconazole; tolnaftate; chloroquine (antimalarial); mefloquine hydrochloride; quinine; ivermectin (anthelmintic); piperazine; pyrvinium pamoate; thiabendazole; aciclovir; ganciclovir sodium; interferons; valaciclovir hydrochloride; and zidovudine.

Suitable anti-migraine agents include: dihydroergotamine; ergotamine tartrate; methysergide maleate; pizotifen; and sumatriptan succinate.

Suitable anti-obesity agents include: sibutramine; and phentermine.

Suitable anxiolytics include: alprazolam; buspirone hydrochloride; chlordiazepoxide; clorazepic acid; lorazepam; meprobamate; oxazepam; and prochlorperazine.

Suitable blood modifiers include anti-coagulants, anti-platelet agents, folic acid derivatives and combinations thereof, iron and iron-containing preparations, liver extracts and preparations containing them, hemorrheologic agents and hemostatics.

Suitable contraceptives include: ethinyloestradiol; norgestimate; desogestrel; lynoestrenol; norgestrel; medroxyprogesterone acetate; and progesterone.

Suitable cytokines and lymphokines include interleukin-8; erythropoietin and interleukin-2.

Suitable hormones include: stilboestrol; finasteride; liothyronine sodium; thyroxine sodium; and calcitonin.

Suitable local anaesthetics include: bupivacaine hydrochloride; lignocaine (lidocaine); and prilocaine hydrochloride

A suitable laxative is danihron.

Suitable non-steroidal anti-inflammatory agents (NSAIDs) include: acemetacin; azapropazone; diclofenac; etodolac; fenbufen; fenoprofen calcium; flurbirprofen; ibuprofen; indomethacin; ketoprofen; ketorolac; meclofenamate sodium; mefenamic acid; naproxen; oxaprozin; oxyphenbutazone; phenylbutazone; piroxicam; sulindac; tenoxicam; tiaprofenic acid; meclofenamic acid; and tolmetin sodium.

Suitable vitamins and dietary supplements include: ascorbic acid; carotene (Vitamin A precursor); nicotinic acid/niacin; pantothenic acid; pyrodoxine; retinol; riboflavin; sodium chloride (source of sodium ions); sodium fluoride (oral hygiene/bone density); sodium phosphate (hypophosphataemia); thiamine; vitamin A; vitamin B12; vitamin C; vitamin D; vitamin E; and vitamin K.

The container according to the invention has many applications and uses.

Thus, apart from its use for constituting pharmaceutical formulations for oral delivery for human and veterinary applications, the container can also be used for the constitution of formulations for administration through other routes. For example, the container can be used to administer nasal decongestants and bronchodilators, such that it can be used as an inhaler. Other suitable applications are in the constitution of ophthalmic drinks and for the delivery of skin and mucus membrane agents.

The container according to the invention can also be used for the constitution of injectables in that sterile products can be mixed in the container before administration. One particular use in this regard is in the field of vaccines.

It will be appreciated that the container according to the invention has particular application in geriatric and paediatric medicines.

The container according to the invention can also be used as a component of emergency health care and first aid kits. Thus, apart from the embodiments hereinabove described, the container can contain an antiseptic agent and a pain-killing agent which are constituted before administration to a subject at the sight of an accident. Another example would be a container containing the constituents for use in the treatment of burns.

When the container according to the invention is used to constitute a foodstuff, such foodstuffs would typically include gravies, soups, sauces, dressings, cereals, including instant breakfast cereals, baby food and baby formulations, dietary drinks, fruit and vegetables, but more generally a range of foodstuffs catering for the domestic, catering and ‘dashboard’ or convenience dining markets.

It will be appreciated that the invention has particular application for baby milks or formulas, where the solids can be stored in a compartment and mixed with water before use. This aspect of the invention would have particular advantages where the user does not have access to a clean water supply.

Examples of non-alcoholic beverages include teas, including green tea and herbal teas, coffee, drinking chocolate, slumbermilk, energy drinks, combination drinks and certain dietary drinks.

An example of a combination drink is one which contains more than one constituent, for example, a mineral and a vitamin.

Apart from various alcoholic beverages, the container in accordance with the invention can also be used to formulate preparations for the treatment of alcohol abuse.

Clearly in the case of all of the above embodiments for oral delivery the constituents would be sterilised/pasteurised, as required.

According to a further embodiment of the invention, the formulation is adapted for topical delivery.

Accordingly, the container can be used to deliver a hair dye.

As used herein, the term hair dye embraces permanent and non-permanent hair colourings, highlights and beard dye.

Examples of hair dye active ingredients as used herein are hydrogen peroxide, ammonia, phenylenediamines, resorcinol and steralkonium chloride.

Also contemplated for constitution in a container according to the invention are various types of cosmetics, including hand creams, hand cleansers, liquid make-up, edible make-up, a perfume and a deodorant in one container, two perfumes in one container and tanning agents, including Pre- and post-sun or non-sun types. In the latter regard, examples of tanning agents are prunus armeniaca, prunus armygdalus dulcis.

The container ac cording to the invention can be used to deliver a formulation to the vagina.

According to this embodiment, the formulation can be in the form of a douche.

Preferably, the active ingredient is a probiotic.

Suitable probiotics in this regard correspond to those herein defined above.

Further, preferably, the container also includes a prebiotic.

Examples of suitable prebiotics in this regard are those hereinabove defined.

As indicated above, the volume of the liquid formulation will normally be less than 100 ml, but especially is in the range of 40-80 ml. The container will be of a size which will accommodate the liquid formulation to be administered and the components for forming such formulations, including allowing for variations in state and volume while the formulation is being formed such as changes due to effervescence.

The container, and thus the volume of the liquid formulation, can be up to 5,000 ml, if required. A volume of the order of 5,000 ml would be desirable for example in a sports centre if one requires to dispense large volumes of an energy drink or the like. For large volume containers it would be necessary to use both hands to rotate the container so as to activate the unsealing means.

The container can be used to constitute odour enhancing, aromatherapy, air freshening and vaporising agents, hereinafter referred to collectively as air fresheners.

Thus, according to a further embodiment of the invention the container is used to constitute an air freshener.

Other applications and uses for the container in accordance with the invention are for the constitution of cleaning agents and detergents for use in both the domestic and industrial sectors.

According to a firther embodiment, the container is used to constitute a fuel.

Preferably, the respective constituents are petrol and an oil.

Further, preferably, the petrol and oil are in a ratio of 40:1 for use in a two-stroke engine.

According to a still further embodiment of the invention the liquid and the or each active ingredient are constituents used to form a formulation used in building construction or in painting and decorating.

Applications in this regard would include paints, glass fibre mixes, materials used in silicone moulding, what are conventionally referred to as “hard wall”, namely materials used in the construction industry where a power is mixed with water for plastering, more particularly conventional plasters and fillers.

Further examples of use of the container according to the invention are in the agricultural and horticultural sectors, such as use of the container for the constitution of fertilisers.

Further uses for the container in accordance with the invention would be in the area of rehydration products generally.

MODES FOR CARRYING OUT THE INVENTION

The invention will be further illustrated by the following Examples.

The formulations prepared in the following Examples 1-14 were carried out on a laboratory scale with a view to scale-up. The ingredients used and the relative amounts reflect those that may be used, when manufactured in accordance with the invention in sealed containers as hereinafter described in greater detail.

The formulations of Examples 1-10 are examples of active ingredients which are either unstable or insoluble in an aqueous based medium. The formulations of Examples 11 and 12 are examples of formulations where the active ingredient is soluble and stable in an aqueous based medium.

Examples 13 and 14 are examples of methodology and trials used to optimise formulations for administration frdm a container in accordance with the invention.

EXAMPLE 1

Paracetamol Formulation (1000 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Acetaminophen100059.17% 
Ascorbic Acid1005.92%
Citric Acid1207.10%
Sodium Bicarbonate603.55%
Potassium Hydrogen603.55%
Bicarbonate
Dextrose201.18%
Caffeine301.78%
Saccharin25014.79% 
Strawberry Flavouring502.96%
TOTAL FOR A DOSE1690 100%

The components were weighed out into a suitable container sold under the Trade Mark SECURITAINER and then mixed by shaking for five minutes. The container was checked every two minutes and any powder removed from the sides of the container with a spatula. The mixture was checked to ensure the uniformity of the blend and the visual appearance was checked. A sample of the product was taken for analysis and the quantity of the active ingredient was determined using HPLC.

The visual appearance of the formulation in water was also assessed and was found to be a white to off-white effervescent suspension.

For processing multiple doses, the amount of active ingredient and excipients are increased accordingly.

EXAMPLE 2

Aspirin Formulation (500 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Acetylsalicylic Acid50042.02% 
Ascorbic Acid1008.40%
Citric Acid12010.08% 
Sodium Bicarbonate605.04%
Potassium Hydrogen Bicarbonate605.04%
Dextrose201.68%
Caffeine302.52%
Saccharin25021.01% 
Strawberry Flavouring504.20%
TOTAL FOR A DOSE1190 100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 3

Ibuprofen Formulation (200 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
4-Isobutyl-Alpha-Methylphenylacetic20023.53%
Acid (Ibuprofen)
Citric Acid12014.12%
Sodium Bicarbonate60 7.06%
Potassium Hydrogen Bicarbonate60 7.06%
Cyclodextrine10011.76%
Codeine10 1.18%
Saccharin25029.41%
Strawberry Flavouring50 5.88%
TOTAL FOR A DOSE850  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 4

Diclofenac Formulation (100 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Diclofenac sodium10015.15% 
Citric Acid12018.18% 
Sodium Bicarbonate609.09%
Potassium Hydrogen Bicarbonate609.09%
Cyclodextrine10015.15% 
Caffeine304.55%
Saccharin12518.94% 
Sucrose406.06%
Flavouring253.79%
TOTAL FOR A DOSE660 100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 5

Amitripyline Formulation (150 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Amitriptyline15025.82%
Citric Acid12020.65%
Sodium Bicarbonate6010.33%
Potassium Hydrogen Bicarbonate6010.33%
Benzalkonium Chloride1 0.17%
Sucrose40 6.88%
Saccharin12521.52%
Flavouring25 4.30%
TOTAL FOR A DOSE581  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 6

Amoxapine Formulation (150 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Amoxapine15025.82%
Citric Acid12020.65%
Sodium Bicarbonate6010.33%
Potassium Hydrogen Bicarbonate6010.33%
Benzalkonium Chloride1 0.17%
Saccharin12521.52%
Sucrose40 6.88%
Flavouring25 4.30%
TOTAL FOR A DOSE581  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 7

Chlorpheniramine Maleate (4 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Chlorpheniramine maleate4 0.92%
Citric Acid12027.59%
Sodium Bicarbonate6013.79%
Potassium Hydrogen Bicarbonate6013.79%
Benzalkonium Chloride1 0.23%
Sucrose40 9.20%
Saccharin12528.74%
Flavouring25 5.74%
TOTAL FOR A DOSE435  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 8

Cetirizine Dihydrochloride (10 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Cetirizine dihydrochloride10 2.27%
Citric Acid12027.21%
Sodium Bicarbonate6013.61%
Potassium Hydrogen Bicarbonate6013.61%
Benzalkonium Chloride1 0.23%
Sucrose40 9.07%
Saccharin12528.34%
Flavouring25 5.66%
TOTAL FOR A DOSE441  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 9

Bisacodyl Formulation (10 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Bisacodyl10 2.27%
Citric Acid12027.21%
Sodium Bicarbonate6013.61%
Potassium Hydrogen Bicarbonate6013.61%
Benzalkonium Chloride1 0.23%
Saccharine12528.34%
Chocolate Flavouring25 5.66%
Sucrose40 9.07%
TOTAL FOR A DOSE441  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 10

Danthron (15 mmg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Danthron15 3.36%
Citric Acid12026.91%
Sodium Bicarbonate6013.45%
Potassium Hydrogen Carbonate6013.45%
Banzalkonium Chloride1 0.22%
Sucrose40 8.97%
Saccharin12528.03%
Strawberry Flavouring25 5.61%
TOTAL FOR A DOSE446  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 1.

EXAMPLE 11

Isosorbide Mononitrate Formulation (20 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Isosorbide Mononitrate20 4.44%
Citric Acid12026.61%
Sodium Bicarbonate6013.30%
Potassium Hydrogen Bicarbonate6013.30%
Benzalkonium Chloride1 0.22%
Sucrose40 8.87%
Saccharin12527.72%
Flavouring25 5.54%
TOTAL FOR A DOSE451  100%

The components were weighed out into a container sold under the Trade Mark SECURITAINER and then mixed by shaking for five minutes. The container was checked every two minutes and any powder removed from the sides of the container with a spatula. The mixture was checked to ensure the uniformity of the blend and the visual appearance checked. The single dose was added to a bottle to which sterile water was added. A sample of the product was taken for analysis and the quantity of the active ingredient was determined using HPLC. The visual appearance of the formulation in water was also assessed.

For processing multiple doses, the amount of active ingredient and excipients are increased accordingly.

EXAMPLE 12

Adrenaline Formulation (50 mg Dose)

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Adrenaline5010.40%
Citric Acid12024.94%
Sodium Bicarbonate6012.47%
Potassium Hydrogen Bicarbonate6012.47%
Benzalkonium Chloride1 0.21%
Sucrose40 8.32%
Saccharin12525.99%
Flavouring25 5.20%
TOTAL FOR A DOSE481  100%

The formulation was prepared and tested in the same manner as for the formulation of Example 11.

EXAMPLE 13

Acetaminophen Formulation

First Formulation:

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Acetaminophen100044.44%
Ascorbic Acid100 4.44%
Citric Acid50022.22%
Sodium Bicarbonate30013.33%
Potassium Hydrogen Bicarbonate30013.33%
Dextrose20 0.89%
Caffeine30 1.33%
TOTAL FOR A DOSE2250  100%

Blends of the above components were tested in three different volumes df water: 20 ml, 40 ml and 80 ml in different containers.

Results:

Whereas good reaction and suspension of acetaminophen was obtained with 80 ml of water in a bottle, it was considered that a lesser volume of water would be preferable.

In the case of 40 ml, three different containers were tested, namely a graduated cylinder, a beaker and a bottle. In the case of the graduated cylinder, a volume of bubbles (˜60 ml) was observed. Furthermore, quite an amount of the acetaminophen stayed on the sides of the respective containers and on the surface of the water. After fifteen minutes the acetaminophen settled to the bottom of the bottle.

In the case of a volume of 20 ml, again three different containers were investigated, namely a beaker, a sampling container with cap and a small bottle. In each case a considerable amount of foam and gas was observed. Again the acetaminophen did not remain in suspension, with acetaminophen observed on the sides of the containers, on the top of the water and in the bottom of the respective containers.

Second Formulation:

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTSMg for a dose% W/w
Acetaminophen100078.74% 
Ascorbic Acid1007.87%
Citric Acid604.72%
Sodium Bicarbonate302.36%
Potassium Hydrogen Bicarbonate302.36%
Dextrose201.57%
Caffeine302.36%
TOTAL FOR A DOSE1270 100%

In the case of the second formulation a single volume (20 ml) in two different containers were investigated, namely a small bottle and a sampling container with cap.

The result obtained with the second formulation was that there was little generation of foam and an amount of acetaminophen remained on the top of the water. However, overall the visual appearance of the formulation was improved relative to the first formulation.

Conclusion:

It was found that acetaminophen is not stable in water and does not remain in suspension. However, the generation of gas and bubbles can be minimised by decreasing the quantity of the effervescing components, namely citric acid, sodium bicarbonate and potassium hydrogen carbonate so as to obtain a ready-to-drink formulation which can be administered from a container in accordance with the invention.

EXAMPLE 14

Ibuprofen Formulation Test

First Formulation:

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a dose% W/w
Ibuprofen20062.50%
Citric Acid6018.75%
Sodium Bicarbonate30 9.38%
Potassium Hydrogen Carbonate30 9.38%
TOTAL FOR A DOSE320  100%

Two volumes of water were tested, namely 20 ml and 40 ml in two different containers, namely a small bottle and a beaker.

Results:

    • Only a few bubbles were observed; some particles were observed in suspension and on top of the water.
    • The water becomes white.
      Second Formulation:

The formulation was prepared from the following components and in the indicated amounts.

COMPONENTMg for a cap% W/w
Ibuprofen20045.45%
Citric Acid12027.27%
Sodium Bicarbonate6013.64%
Potassium Hydrogen Carbonate6013.64%
TOTAL440  100%

One volume of water was tested, namely 20 ml, and a single container, namely a small bottle.

Results:

    • Foam was observed initially.
    • Following shaking a few bubbles were observed.
    • No particles of ibuprofen were observed in the water.
    • The water becommes white.
      Conclusion:

In the case of the above two formulations, the behaviour of ibuprofen in water was tested and the generation of bubbles was optimised by increasing the quantity of citric acid, sodium bicarbonate and potassium hydrogen carbonate.

Of the two formulations, the second formulation had the better properties.

The conclusion w as that ibuprofen is not stable in water and it does not remain in suspension. However, it is suitable for administration as a formulation from a container in accordance with the invention.

EXAMPLE 15

Probiotic Formulation

(0.1 Gram Dose)

A probiotic formulation was prepared from the following ingredients:

COMPONENTDose (g)% W/w
Probiotic: Lactobacillus0.1 1.5%
acidophilus
Prebiotic: Inulin/5.579.7%
fructooligosaccharide
Cholesterol lowering agent:1.318.8%
Sterol ester
TOTAL FOR A DOSE6.9 100%

Process:
  • Step 1: The Lactobacillus acidophilus, dual coated lactic acid bacteria obtained from Cell Biotech Ltd., Seoul, South Korea, and sold under the Trade Mark Duolac, inulin/fructooligosaccharide (Frutafit CLR (Trade Mark)) obtained from Sensus Ingredients and sterol ester (Vegapure 67 WDP (Trade Mark)) obtained from Cognis were weighed out in an amount sufficient for 10 doses.
  • Step 2: The three components were added to a 1 litre cylindrical container and thoroughly mixed by vigorously shaking the container for 2 minutes. An optimum mixing time of 2 minutes was determined after a number of mixing trials. This 2 minute mixing time resulted in a homogeneous blend being formed.
  • Step 3: A single dose of the blend obtained in Step 2 was added to the second compartment of a two-part container according to the invention. Purified water (40 ml), obtained from Reagecon, Shannon, Ireland, was added to the first compartment. The outer cover was twisted clockwise to release the seal and allow the water to mix with the powder blend. This mixture was vigorously shaken for 5 seconds. Finally, the cover was removed by twisting it in an anti-clockwise direction and the resultant aqueous medium was assessed as follows:
    • Solubility of the blend in the aqueous medium.
    • Traces of powdered residue on the walls of the base.
      Results:
  • A completely aqueous medium was achieved.
  • No powdered residue remained on the walls of the container.
  • Adding flavours (0.2% Cranberry, 0.2% Tropical, 0.2% Orange or 0.2% Apple—supplied by Synergy Flavours) to the purified water had no adverse affect on the solubility of the blend.

Example 15 was repeated using the following probiotics with comparable results:

SourceProbiotic
Cell Biotech, Ltd.Streptococcus thermophilus
Bifidobacterium longum
Acidophilus lactococcus
Institut RosellLactobacillus acidophilus
Bifidobacterium longum
Streptococcus thermophilus
Lactobacillus acidophilus (micro
encapsulated)
Bifidobacterium longum (micro
encapsulated)
Streptococcus thermophilus (micro
encapsulated)
Brewster FoodsLactobacillus acidophilus
Bifidobacterium bifidum
DaniscoLactobacillus acidophilus
Bifidobacterium lactis
Nebraska CulturesLactobacillus brevis
Lactobacillus bulgaricus
Lactobacillus casei
Bifidobacterium lactis
Streptococcus thermophilus

EXAMPLE 16

Prebiotic Formulation

(5.5 Gram Dose)

A prebiotic formulation was prepared from the following ingredients:

COMPONENTDose (g)% W/w
Prebiotic: Native5.579.7%
inulin/fructooligosaccharide
Probiotic: Streptococcus0.1 1.5%
thermophilus
Cholesterol lowering agent:1.318.8%
Sterol ester
TOTAL FOR A DOSE6.9 100%

Process:
  • Steps 1-3 were carried out as in the case of Example 15 except that the container was shaken vigorously for 10 seconds in Step 3. The Streptococcus thermophilus was obtained from Cell Biotech Ltd., Seoul, South Korea, the native inulin/fructooligosaccharide (Frutafit IQ (Trade Mark)) was obtained from Sensus Ingredients and the sterol ester (Vegapure 67 WDP (Trade Mark)) was obtained from Cognis.
    Results:
  • A completely aqueous solution was obtained.
  • Adding flavours (0.2% Cranberry, 0.2% Tropical, 0.2% Orange or 0.2% Apple—supplied by Synergy Flavours) to the purified water had no adverse affect on the solubility of the blend.

Example 16 was repeated using the following probiotics with comparable results:

SourcePrebioticTrade Mark
Orafti Active FoodOligofructoseRaftilose P95
Ingredients
Orafti Active FoodInulinRaftiline GR
Ingredients
Cosucra WarcoingOligofructoseFibrulose F97
Cosucra WarcoingInulinFibruline Instant

EXAMPLE 17

Cholesterol Lowering Formulation

(1.3 Gram Dose)

A cholesterol lowering formulation was prepared from the following ingredients:

COMPONENTDose (g)% W/w
Cholesterol lowering agent:1.318.8%
Phytosterol
Probiotic: Bifidobacterium0.1 1.5%
bifidum
Prebiotic: Native inulin5.579.7%
TOTAL FOR A DOSE6.9 100%

Process:
  • Steps 1-3 were carried out as in the case of Example 16. The Bifidobacterium bifidum was obtained from Brewster Foods, the native inulin/fructooligosaccharide (Frutafit IQ (Trade Mark)) was obtained from Sensus Ingredients and the phytosterol, CardioAid-M (Trade Mark), was obtained from ADM-Archer Daniels Midland Company.
    Results:
  • A completely aqueous solution was achieved.
  • Adding flavours (0.2% Cranberry, 0.2% Tropical, 0.2% Orange or 0.2% Apple—supplied by Synergy Flavours) to the purified water had no adverse affect on the solubility of the blend.

Example 17 was repeated using the following cholesterol lowering agents with comparable results:

Cholesterol lowering
SourceagentTrade Mark
ADMPhytosterol esterCardioAid-GA
ADMPhytosterol-sucroseCardioAid-WD
fatty acid ester
complex

Ascorbic Acid (0.5 g) supplied by O'Brien Ingredients and Vitamin E (0.05 g) supplied by Eastman were successfully incorporated into blends as described in each of Examples 15-17. In each case the quantity of prebiotic used was reduced accordingly.

EXAMPLES 18-20

Two Part Polymer Formulations

Shore A
ExampleBaseCatalystHardness
18Silicone Moldsil FMoldsil thixo additive22
10 parts1 part
19Polyurethane PolyPoly 74-65 additive65
74-65 base1 part
 4 parts
20Polyurethane PolyPoly 74-40 additive40
74-40 base1 part
 2 parts

Using a two-part container according to the invention in each case, the catalyst (contained in the first compartment) was allowed to mix with the base (contained in the second compartment) when the seal was opened. In these examples, all materials were supplied by W.P. Notcutt Ltd.
These two part systems cure when the two components are mixed together. Use of a container according to the invention ensures that the correct amount of catalyst is used each time, removing the chance of human error.

EXAMPLES 21-22

Two Part Hair Colour Formulations

Hair colourColour activating
ExampleproductColourcreme
21Laboratoires1 part1 part 
Garnier (Two part
conditioning
crème colourant)
22Clairol nice' n1 part2 parts
easy (nice' n easy
is a Trade Mark)
(Natural looking
colour-level 3-
permanent)

Using a two-part container according to the invention in each case, allows a ‘simple clean solution’ to mixing two-part hair colours. The colour-activating agent or developer (contained in the first compartment) was allowed to mix with the colourant (contained in the second compartment) when the seal was opened. The activated hair colour was then applied in conventional manner. Thus, use of the container according to the invention removes the chance of human error in the preparation of hair colours.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a container for constituting a formulation in liquid form, according to the invention;

FIG. 2 is a cross section on line II-II of FIG. 1;

FIG. 3 is an exploded view of the container of FIG. 1;

FIG. 4 is a schematic view of a second embodiment of a container according to the invention;

FIG. 5 is a cross section on line V-V of FIG. 4;

FIG. 6 is an exploded view of the container of FIG. 4;

FIG. 7 is a schematic representation of a third embodiment of a container according to the invention;

FIG. 8 is a cross section on line VIII-VIII of FIG. 7, with the seal in the closed position;

FIG. 9 is a cross section of the container of FIG. 7, with the seal in the open position;

FIG. 10 is an exploded view of the container of FIG. 7;

FIG. 11 is a schematic representation of a fourth embodiment of a container according to the invention;

FIG. 12 is a cross section on line XII-XII of FIG. 11, with the seal in the closed position; and

FIG. 13 is a cross section of the container of FIG. 11, with the seal in the open position;

Referring to FIG. 1 there is indicated, generally at 10, a container for oral delivery of a pharmaceutical formulation in liquid form, the container 10 having a first section 11 for holding a quantity of potable liquid, and a second section 12 for holding a quantity of active ingredient.

The container 10 has a bottled shape termination at one end 13 thereof with a neck portion 14, to which a tamper-proof closure 15 is secured for storage.

The second section 12 is attached to the first section 11, such that the two sections can be moved relative to each other about the longitudinal axis of the container 10.

Referring to FIG. 2, the container 10 can be seen in mbre detail. Closure 15 is secured to the neck portion 14 of the first section 11. A thread 16 on an internal surface 17 of the closure 15 mates with a complementary thread 18 on the neck portion 14 of the first section 11.

At other end 19 of the first section 11, a circumferential shoulder portion 20 has a circumferential groove 21 therein.

The second section 12 is cylindrical in shape and has a base section 22 at one end 23 thereof, and a circumferential formation 24 at other end 25 thereof, which forms a snap fit with the groove 21 on the first section 11.

A circular sealable partition 26 separates the first section 11 from the second section 12. The partition 26 has a plurality of upstanding tabs 27 about circumference 28 thereof. These tabs 27 have threads 29 on the exterior surface 30 thereof, which threads 29 mate with a complementary thread 31 on interior surface 32 of the first section 11. In the storage state, the partition 26 forms a seal with the end 19 of the first section 11.

A plurality of formations 33 are arranged on inner surface 34 of the second section 12. These formations 33 locate at ends 35 thereof in a plurality of slots (not shown) in lower surface 36 of the partition 26.

In use, the first section 11 is partially filled with a potable liquid and an active ingredient is placed in the second section 12. During storage the liquid and active ingredient are kept apart by the sealable partition 26. When it is desired to form and imbibe the formulation, the two sections 11 and 12 are moved in a twisting motion relative to each other. This twisting movement causes the formations 33 to engage the edges of the slots in the partition 26, causing it to unscrew away from the first section 11, thus breaking the seal between the section 11 and the partition 26, resulting in the passage of the potable liquid into the second section 12. The container 10 is then shaken to mix the active ingredient with the potable liquid to form the formulation, which can then be imbibed following removal of the closure 15.

Referring to FIG. 3, the container of FIG. 1 is shown in an exploded view. The container is filled by screwing the partition 26 into the end 19 of the first section 11 to form a seal therebetween. The section 11 is then filled with a quantity of potable liquid and the tamper-proof closure 15 is screwed onto the neck portion 14. A quantity of active ingredient is placed in the second section 12 and the two sections 11, 12 are joined together by snapping the formation 24 into the groove 21, while ensuring that the formations 33 are located in the slots in the partition 26.

Referring to FIG. 4, there is indicated, generally at 40, a second embodiment of a container according to the invention. The container 40 is bottle-shaped and has a first section 41 for holding a quantity of liquid and a second section 42 for holding a quantity of active ingredient. The two sections 41, 42 are connected by a waist portion 43. The first section 41 terminates at one end 44 thereof with a neck portion 45 to which is secured a tamper-proof closure 46.

Referring to FIG. 5, the container 40 is seen in cross section. A sealable partition 47 is seated in a seal 48, which seal 48 is located in the waist portion 43 of the container 40.

A cylindrically-shaped elongate connecting member 49 is attached at one end 50 thereof to the sealable partition 47. A circumferential collar section 51 is secured on other end 52 of the elongate connecting member 49. The collar section 51 sits on an inner shoulder 53 located on the neck portion 45 of the container 40. A thread 54 on the collar section 51 mates with a complementary thread 55 on inner surface 56 of closure 46.

In use, a quantity of active ingredient is placed in section 42. The sealable partition 47 is seated in the seal 48 and a quantity of potable liquid is placed in section 41. The closure 46 is then screwed onto a thread 57 on the neck portion 45 of the container 40. When it is desired to form and imbibe the formulation, the closure 46 is screwed further onto the neck portion 45 of the container 40 until it falls off the thread 57 on the neck portion 45 and is then free to rotate therearound. Further rotation causes the thread 54 on the collar section 51 to engage with the complementary thread 55 on the inner surface 56 of the closure 46. Further movement of the closure 46 then causes the partition 47 to be lifted out of the seal 48, allowing the potable liquid to enter the second section 42 and to mix with the active ingredient therein. Once the active ingredient has been mixed with the liquid the closure 46 can be removed and the resulting formulation can be imbibed by the user.

The elongate connecting member 49 is cylindrical in shape and has a plurality of longitudinal slots 58 on outer surface 59 thereof. These slots 58 permit the free passage of liquid within the first compartment 41.

Referring to FIG. 6, the container 40 is shown in exploded view. The two sections 41, 42 and the waist portion 43 therebetween are blow moulded as a single plastics unit. The seal 48 can be located on the partition 47 prior to the placement of these components in the container 40.

Referring to FIG. 7, there is indicated, generally at 70, a third embodiment of a container according to the invention. The container 70 has an elongate outer body 71 split into a first section 72 and a second section 73, along the longitudinal axis thereof. The first section 72 is made up of an outer cover 74 and a tear strip 75, the tear strip 75 being releasably attached to the outer cover 74 along an edge 76 thereof.

Referring to FIG. 8, the container 70 has an inner chamber 77, which inner chamber 77 is divided into a first compartment 78 and a second compartment 79 by a seal 80. In FIG. 8 the seal 80 is shown in a closed position, wherein the first compartment 78 and the second compartment 79 are sealed thereby.

The seal 80 is mounted at one end 81 of an elongate member 82, which elongate member 82 is located within the first compartment 78 of inner chamber 77. The first compartment 78 is generally cylindrical in shape with an opening 83 at one end 84 thereof, which opening 83 is adapted to seat the seal 80 in the closed position. End 84 of the first compartment 78 is in the form of a collar section, the end and the collar section herein being denoted collectively by the reference numeral 84, which extends beyond opening 83, and which collar section 84, has a larger diameter than that of opening 83.

The outer cover 74 is connected to the collar section 84 by a snap fit 85 and the second section 73 is connected to the collar section 84 by a snap fit 86.

Other end 87 of the first compartment 78 has an opening 88 therein. The end 87 is seated within an upstanding annular wall 89 on an inner surface 90 of the outer cover 74, which inner surface 90 seals the end 87. Other end 91 of the elongate member 82 is located within the opening 88. The end 91 is open and is adapted to accommodate an inner upstanding annular wall 92 on the inner surface 90 of the outer cover 74. The inner upstanding annular wall 92 has four open-ended slots 93 therein, with each slot 93 cooperating with a complementary formation 94, located at the other end 91 of elongate member 82, to cause movement of the seal 80 from the closed position (FIG. 8) to the open position (FIG. 9).

Referring to FIG. 9, four cut-outs 95 at the end 81 of the elongate member 82 allow free passage of the contents of the inner chamber 77, with the seal 80 in the open position.

Referring to FIG. 10, the container 70 is illustrated in an exploded view, showing the outer cover 74, the first compartment 78, the elongate member 82 and the second section 73 separated out for clarity.

The formations 94 on the other end 91 of the elongate member 82 can be seen in more detail. Each formation 94 is in the form of a flexible flange 96 with a rectangular projection 97 mounted at end 98 thereof. An outer edge 99 of each rectangular projection 97 is locatable in a corresponding slot 93 on the outer cover 74 (FIGS. 8 and 9). Edge 100 of each flange 96 slopes away from the end 91 and tails off as a cut 101 in surface 102 of the elongate member 82. It is the cut 101 which imparts flexibility to the flange 96.

Four sloping tracks 103 are located on inner surface 104 of the first compartment 78 at the end 87 thereof. When the container 70 is assembled, with the seal 80 in the closed position, the end 91 of the elongate member 82 is flush with the end 87, with each rectangular flange 96 located within a first groove 105 on the inner surface 104, and with the outer edge 99 of each rectangular projection 97 being located in its corresponding slot 93. In the same position the sloping edge 100 of each flange is resting on a corresponding sloping track 103, which sloping track 103 is fully located within the corresponding cut 101. Rotation of the outer cover 74, in the direction of arrow A, causes the elongate inner body 82 to also turn relative to the first compartment 78, with each sloping edge 100 riding up the corresponding track 103 and each rectangular projection 97 moving up the corresponding slot 93. When each rectangular projection 97 reaches and drops into a second groove 107 on the inner surface 104, further movement of the elongate inner body 82 is prevented and the seal 80 has reached the open position.

Further rotation of the outer cover 74 in the same direction has no effect on the position of the elongate member 82 as the rectangular projections 97 will disengage from the corresponding slots 93.

When the container 70 is assembled, edge 108 of the second section 73 abuts a circumferential projecting wall 109 on the collar section 84 of the first compartment 78. Four projections 110 on the edge 108 are locatable in corresponding slots 111 in the circumferential projecting wall 109 and prevent the second section 73 from moving relative to the first compartment 78.

The annular tear strip 75 also abuts the circumferential projecting wall 109, when assembled. Four resilient pins 112 are located around edge 113 of the annular strip 75. Each pin 112 is shaped so as to ride in and out of a plurality of complementary slots 114 in the circumferential projecting wall 109, when the outer cover 74 is turned in the direction of arrow A. However, if the outer cover 74 is moved in the opposite direction, each pin 112 will drop into a complementary slot 114 and the tear strip 75 will become locked in position relative to the inner compartment 78. Any further attempt to move the outer cover 74 in that direction will cause the outer cover 74 to separate from the tear strip 75, along a join 115. The join 115 has a saw tooth profile and this causes the snap fit 85 to disengage facilitating removal of the outer cover 74 from the container 70.

In order to assemble the container 70 for use, the elongate inner element 82 is placed within the first compartment 78 with the seal 80 in the closed position. An active ingredient is placed in the second compartment 79, and the second section 73 is attached to the first compartment 78. An amount of liquid is placed in the first compartment 78 and the outer cover 74 is attached thereto. The assembled container 70 is then placed in a suitable storage receptacle (not shown) until it is required to constitute the formulation.

When it is required to constitute the formulation, the container 70 is removed from the storage receptacle, and the outer cover 74 is rotated in the direction indicated by arrow A, while holding the second section 73. This rotating movement moves the seal 80 from the closed position to the open position allowing mixing of the active ingredient with the quantity of liquid. When mixing is complete the outer cover 74 is removed by reversing the direction of rotation and the formulation can then be removed from the container 70.

In an alternative embodiment (not illustrated) of the cover 74 of the container 70, each open-ended slot 93 in the inner upstanding annular wall 92 is replaced by a cup into which the rectangular projection 97 sits in the closed position. Rotation of the outer cover 74, in the direction of arrow A, causes the elongate inner body 82 also to turn as a wall of each cup pushes the corresponding rectangular projection 97 in the same direction.

When each rectangular projection 97 reaches and drops into the second groove 107, it has cleared the corresponding cup wall and thus further movement of the outer cover 74 in the same direction has no effect on the position of the elongate member 82.

Referring to FIG. 11, there is indicated, generally at 120, a fourth embodiment of a container according to the invention. The container 120 has an elongate outer body 121 split into a first section 122 and a second section 123, along the longitudinal axis thereof. The first section 122 is made up of an outer cover 124 and a tear strip 125, the tear strip 125 being releasably attached to the outer cover 124 along an edge 126 thereof.

Referring to FIG. 12, the container 120 has an inner chamber 127, which inner chamber 127 is divided into a first compartment 128, a second compartment 129 and a third compartment 130 by a seal 131. In FIG. 12 the seal 131 is shown in a closed position, wherein the first compartment 128, the second compartment 129 and the third compartment 130 are sealed thereby.

The seal 131 is mounted at one end 132 of an elongate member 133, which elongate member 133 is located within the first compartment 128 of the inner chamber 127. The first compartment 128 is generally cylindrical in shape with an opening 134 at one end 135 thereof, which opening 134 is adapted to seat the seal 131 in the closed position.

The outer cover 124 and the second section 123 are mounted over end 135 of the first compartment 128 and are separated by an annular wall 136 projecting from end 135. The outer cover 124 and second section 123 are held in place by snap fit connections 137 and 138, respectively.

Other end 139 of the first compartment 128 has an opening 140 therein. The end 139 is seated within an upstanding annular wall 141 on an inner surface 142 of the outer cover 124, which inner surface 142 seals the end 139. Other end 143 of the elongate member 133 is located within the opening 139. The end 143 is open and is adapted to accommodate an inner upstanding annular wall 144 on the inner surface 142 of the outer cover 124. The inner upstanding annular wall 144 has four open-ended slots 145 therein, with each slot 145 cooperating with a complementary formation 146, located at the other end 143 of the elongate member 133, to cause movement of seal 131 from the closed position (FIG. 12) to the open position (FIG. 13).

Referring to FIG. 13, four cut-outs 147 at the end 132 of the elongate member 133 allow free passage of the contents of the inner chamber 127, with the seal 131 in the open position. A widened out section 148 of the first compartment 128 also assists in the free passage of the contents of the inner chamber 127.

In use, rotation of the outer cover 124, relative to the second section 123, in the direction of arrow B (FIG. 11) causes the seal 131 to move from the closed position (FIG. 12) to the open position (FIG. 13). The mechanism (not shown), for causing the elongate member 133 to move, is similar to that of the embodiment illustrated in FIGS. 7-10. However, in this embodiment the elongate member 133 is drawn towards the inner surface 142 of outer cover 124 rather than being moved away from the inner surface 142, as the seal 131 is moved into the open position.

Referring again to FIG. 11, movement of the outer cover 124 in a direction opposite to arrow B, causes a set of pins 149 on the tear strip 125 to fall into complementary slots 150 in the wall 136, causing the pins 149 to lock. Further movement in this direction results in the shearing of a join 151 along the edge 126 and the outer cover 124 can then be removed from the container 120. This removal is facilitated by the saw tooth profile of the edge 126.