WO2011128634A2

WO2011128634A2 - Over the counter pharmaceutical compositions

Info

Publication number: WO2011128634A2
Application number: PCT/GB2011/000564
Authority: WO
Inventors: Kurt Ingar Draget; Ingvild Johanne Haug; Steinar Johan Engelsen; Tore Seternes
Original assignee: Probio Asa; Cockbain, Julian
Priority date: 2010-04-14
Filing date: 2011-04-11
Publication date: 2011-10-20
Also published as: GB201006214D0; WO2011128634A3

Abstract

This invention provides an oral pharmaceutical composition comprising an over the counter drug substance contained in a physiologically tolerable gelled oil-in-water emulsion.

Description

Over the Counter Pharmaceutical Compositions

This invention relates to over the counter pharmaceutical compositions in the form of gelled oil-in-water emulsions and to methods of treatment of a human subject therewith.

Non-prescription or over the counter (OTC) drug substances are used to treat a number of common complaints, particularly, but not limited to, pain (e.g. headaches and migraines as well as ear infections which do not require antibiotics), allergies (e.g. itchy eyes/nose/throat, sneezing), coughs and colds, fever, runny noses, congestions, hoarseness, and sore throats.

Many OTC drug substances are formulated as combinations, often as suspensions. Such suspensions often have an unpleasant taste and/or odour as well as short stability. Cough syrups in particular are often unpleasant to ingest, due to foul taste, mouthfeel or smell. Accordingly, any therapeutic or prophylactic dosage regime which involves the consumption of unpleasant tasting dose units or nasty smelling dose units is inherently at risk of patient non-compliance, especially when the patient is a child.

Moreover, when the unit dose of a drug substance is large, the oral unit dosage forms, e.g. tablets or capsules, may likewise be large and so difficult for elderly or young patients to swallow, especially if they have a sore throat, and moreover may cause a gagging reaction even with healthy adults. As a result, any therapeutic or prophylactic dosage regime which involves the consumption of large numbers of dose units or numbers of large, difficult to swallow, dose units is also inherently at risk of patient non-compliance.

When the drug substance is in the form of a suspension it is cumbersome for the patient or patient's carer to have to carry bottle and dispensing unit when out and about.

When the drug substance is in the form of a tablet there is the problem that in order to swallow a tablet or capsule many patients also require to swallow a quantity of liquid, e.g. water, to ensure the tablet or capsule reaches the stomach and to avoid a gag reaction. Many drug substances are formulated as suspensions which require the addition of clean water before consumption.

This need for water when taking an oral pharmaceutical or for preparing a diluted suspension is problematic when the patient is in a region where clean water is not readily available or when taking a drink of water to facilitate oral administration of the drug substance might draw attention to the fact that a drug is being

administered and so embarrass the patient.

For some drug substances it is possible to use a chewable tablet, a suckable lozenge, or a film that dissolves in the mouth as the vehicle for the drug substance. Nevertheless, this is not feasible where the drug substance has a bitter or unpleasant taste or where it is primarily intended to be taken up lower down the gastrointestinal tract.

Thus there is a need for over the counter compositions which may be administered orally with increased ease of oral intake, chewability, masking or foul taste and improved palatability which leads to better patient compliance and preferably without the need for an accompanying draft of water.

We have now found that this need is satisfactorily met by formulation of the drug

Thus viewed from one aspect the invention provides an oral pharmaceutical composition comprising an over the counter drug substance contained in a physiologically tolerable gelled oil-in-water emulsion.

By "over the counter drug substance" is meant any substance available without prescription and includes vitamins which classify as drug substances for regulatory approval, e.g. vitamins A, K or D (e.g. ergcalciferol, alphacalcidol and calcitriol), vitamin E, water soluble vitamins and other substances which have therapeutic, prophylactic or nutraceutical effect.

Suitable over the counter drug substances include analgesics or anti-fever agents such as aspirin, acetaminophen, ibuprofen, naproxen, codeine, tramadol, hydrocodon, dihydrocodeine, ethylmorphine; first generation antihistamines (which have sedative, antiemetic and/or anticholinergic effects) such as chlorpheniramine, clemastine, diphenhydramine (which is also effective as a sleep aid and against motion sickness), brompheniramine, doxylamine, second generation antihistamines (which have sedative and/or antiemetic effects) such as cetirizin, loratidine; third generation antihistamines such as levocetirizine, desloratidine, fexofenadine;

decongestants such as ephedrine, pseudoephedrine, phenylephrine,

phenylpropanolamine; expectorants such as guaifenesin; antitussives such as dextromethorphan, ethylmorphine and noscapin; and anxiolytics such as

meprobamate. Hoarseness may be treated with an analgesic and an expectorant, e.g. aspirin, acetaminophen, ibuprofen or naproxen in combination with guaifenesin. Anxiolytic drugs such as meprobamate are also included. Caffeine,

dichloralphenazone, isometheptene, pyrilamine, pamabrom, phenyltoioxamine and butalbital are often included in over the counter compositions and may be included in the compositions of the invention. Pharmaceutically acceptable salts of the drugs are also suitable, e.g. the sulphate, maleate, citrate or hydrochloride salts.

Suitable nutraceuticals include the following:

Antioxidants:

- vitamins - A, D, E, K C, B1-12 and folate

- estrogen

- amino acids (taurine, tryptophan, tyrosine, cysteine and homocysteine show antioxidant ability at concentrations which are within the usually reported

physiological ranges)

- lipid lowering agents

- monounsaturated fats

- Flavonoids (several thousands), e.g. polyphenols and flavonoides (including flavonoles, flavones, cathecins and gallic acid, flavonones, anthocyanidines, isoflavonoids

- Caretenoids (e.g. beta carotene, alpha carotene, luteine, zeoxantaine,

xanthophylls, lycopene

- selenium

Other suitable nutraceuticals include: - phytosterols

- sapponins

- Probiotics

- Phytoestrogens (daidzein, lignans)

- dietary fibres (insoluble fibre, beta-glucans, whole grains)

- vitamin-like compounds (L carnitine, choline, inositol, teurine)

- plant extracts (aloe vera, evening primrose oil, garlic, ginger, ginseng, green tea, caffeine.

Particularly preferably the compositions of the invention will contain two or more over the counter drug substances, for example a decongestant and a first generation antihistamine in addition to e.g. an expectorant and/or a painkiller, and/or an antipyretic drug.

Some known over the counter remedies contain both a stimulant (e.g.

decongestants) and a sedative (e.g. antihistamines). Hay fever and cold/flu remedies and the like are thus commonly available in formulations for night-time use and non-drowsy formulations for daytime use. Suspension-based products do not facilitate these varying doses as different doses would have to be measured out according to the time the remedy was to be taken. This leads to poor compliance with dose limits. The present invention allows the production of compositions with

the active drug substances for use at different times or in different circumstances. The different doses could be identified with e.g. colour coding or instructions on the pack, e.g. blister pack.

Suitable drug combinations for use in the invention include:

Guaifenesin and ephedrine

Guaifenesin and phenyleprine

Guaifenesin and pseudoephedrine

Dextromethorphan, acetaminophene, chlorpheniramine and Pseudoephedrine Dextromethorphan and phenyleprine (optionally with chlorpheniramine) (optionally with acetaminophene)

Dextromethorphan and guaifenesin

Dextromethorphan, acetaminophen, phenylephrine (optionally with guaifenesin) Dextromethorphan, pheniramine and phenylephrine

Dextromethorphan, guaifenesin and pseudoephedrine

Dextromethorphan and chlorpheniramine

Dextromethorphan, chlorpheniramine and pseudoephedrine

Dextromethorphan, chlorpheniramine and phenylephrine

Dextromethorphan, chlorpheniramine and acetaminophene

Dextromethorphan, chlorpheniramine, pseudoephedrine and acetaminophene Dextromethorphan, guaifenesine, pseudoephedrine and acetaminophene Brompheniramine and pseudoephedrine

Diphenhydramine and aspirin

Diphenhydramine and pseudoephedrine

Diphenhydramine, acetaminophene and Pseudoephedrine

Diphenhydramine, acetaminophene, doxylamine and pseudoephedrine Diphenhydramine and codeine

Diphenhydramine, codeine, acetaminophene and caffeine

Diphenhydramine and acetaminophene

Loratadine and pseudoephedrine sulphate

Cetirizine and pseudoephedrine HCI

Phenylephrine and acetaminophen (optionally with diphenylamine)

Phenylephrine (optionally with acetaminophen) and chlorpheniramine Phenylephrine (optionally with acetaminophen) and diphenhydramine

-Phenylephrine-and_diphenhy_dramine

Phenylephrine, pheniramine and dextromethorphan

Phenylephrine, pheniramine and acetaminophen

Phenylephrine, pheniramine and dextromethorphan

Phenylephrine and diphenhydramine

Ibuprofen and pseudoephedrine

Ibuprofen and hydrocodone

Acetaminophen, pseudoephedrine and diphenhydramine

Acetaminophen and pseudoephedrine

Acetaminophen and caffeine

Acetaminophen, pseudoephedrine and diphenhydramine

Acetaminophen, pyrilamine (optionally with pamabrom)

Acetaminophen, pyrilamine and caffeine

Acetaminophen, isometheptene and dichloralphenazone Acetaminophen and butalbital

Acetaminophen and diphenhydramine

Acetaminophen and pamabrom

Acetaminophen and tramadol

Chlorpheniramine and Pseudoephedrine

Chlorpheniramine and acetaminophen

Chlorpheniramine and acetaminophen! and pseudoephedrine

Diphenhydramine and aspirin

Diphenhydramine, acetaminophen (optionally with pseudoephedrine)

Brompheniramine, and pseudoephedrine

Brompheniramine, acetaminophene and pseudoephedrine

Aspirin and Phenylpropanolamine

Aspirin and caffeine (optionally with butalbital)

Aspirin and hydrocodone

Aspirin and meprobamate

Aspirin, caffeine and dihydrocodeine

The compositions of the invention are preferably in dose unit form, and each dose until will typically contain 10% to 100%, preferably 50% to 100% of the

recommended daily (or one-off) dose of the particular drug substance. Examples of recommended daily or one-off doses for some of the drug substances mentioned _herein_are^set-OutJnJ5i3jejlJ>eJow_^_

In a particularly preferred aspect, the compositions of the invention are in soft, chewable form.

Where the human recipient is a child, the compositions according to the invention are especially suitable since they can readily and accurately be divided, for example by cutting with a blade, to provide the dosage required for the child's particular age or bodyweight/size. For this reason it is preferred to mark the dose unit (e.g. with surface markings such as a scale of bodyweight, height or age) or its packaging (e.g. the blister or blister cover of a blister-packed gelled emulsion) with indications showing where the gelled emulsion dose unit may be divided to yield a fragment containing the desired dosage. Table 1

Typical daily or one-off drug doses (for adults unless otherwise specified).

Drug/Drug Dosage

combination

Diphenhydramine (D), D:20 mg, acetaminophene: 325mg, caffeine: 15 mg, codeine, codeine 8 mg

acetaminophene and

caffeine

Diphenhydramine (D) DHCI: 25mg, acetaminophene: 500 mg,

HCI, codeine,

ethylmorphine A: 10-20 mg max, C>2 years: 5-10 mg max QID ephedrine A: 20-50 mg BID-QID, C: 0.5-0.75 mg/kg QID. Not to exceed about 3 mg/kg per day if given e.g. 6 times a day aspirin For pain: A: 500- 000 mg TID-QID, C: 10-15 mg/kg QID

For fever: A: 500-1000 mg three to four times a day, C: 10-15 mg/kg QID

Acetaminophen For pain: A: 500-1000 mg QID, C: 20 mg/kg QID

For fever: A:1000 mg QID, C: 20 mg/kg QID

Ibuprofen For pain: A: 600-800 mg TID, C: ~ 5-10 mg/kg TID (QID, not more than 40 mg/kg)

For fever: A:200 mg QID, C: 10/kg mg QID

Naproxen For pain: A: 200-500 mg QID, C: 2.5-5 mg/kg BID (under

50 kg)

For fever: A:250-500 mg BID, C: 2.5-5 mg BID chlorpheniramine A: 2-4 mg BID, C>5 years: 0.5-2 mg twice, 2 to 3 per day dependent on weight

diphenhydramine A: 25-50 mg TID-QID, C: 5 mg/kg per 24 hours taken in

3 or 4 doses

brompheniramine A: 4-8 mg QID, controlled release 6-12 mg BID; C < 6 years: 0.125 mg/kg QID, C>6 years: 2-4 mg TID-QID dependent on weight

cetirizin, A: 10 mg OD, C 6-12 years: 5 mg BID, C 2-6 years: 2.5

OD: Once daily

BID: Twice daily

TID: Three times a day

QID: Four times a day

A = adult dose

C = child dose

Viewed from a further aspect the invention provides a pharmaceutical composition, comprising a drug substance contained in a physiologically tolerable gelled oil-in- water emulsion, wherein said drug substance is an over the counter drug substance for use in medicine.

Viewed from a further aspect the invention provides a pharmaceutical composition, comprising a drug substance contained in a physiologically tolerable gelled oil-in- water emulsion, wherein said drug substance is an over the counter drug substance for use treatment to combat pain (e.g. headaches), allergies (e.g. itchy

eyes/noses/throat, sneezing), coughs and colds, fever, runny noses, congestions, hoarseness, or sore throats.

Viewed from a still further aspect the invention provides the use of an over the counter drug substance contained in a physiologically tolerable gelled oil-in-water emulsion for the manufacture of a medicament for use by oral administration in the treatment of pain (e.g. headaches), allergies (e.g. itchy eyes/noses/throat, sneezing), coughs and colds, fever, runny noses, congestions, hoarseness, or sore throats.

Viewed from a still further aspect the invention provides a method of treatment of a human subject to combat pain (e.g. headaches), allergies (e.g. itchy

eyes/noses/throat, sneezing), coughs and colds, fever, runny noses, congestions, hoarseness, or sore throats which method comprises orally administering to said — subjectan-effectiv.e,amount.ola,provides a pharmaceutical composjtion. _^^corriprising a drug substance contained in a physiologically tolerable gelled oil-in-water emulsion, wherein said drug substance is an over the counter drug substance.

Many over the counter remedies contain substances which may be subject to abuse such as central nervous system stimulants and/or morphine derivatives. In typical compositions, these substances may be removed and thus concentrated by a would-be abuser. The present invention provides such substances in a form which is much less amenable to misuse as the drug substance is incorporated in both an emulsion and a gel.

The drug substance may typically be included in the compositions of the invention at 10% to 100% of its normal oral daily dose, especially 50% to 100%. Besides the drug substance, the compositions of the invention may contain further components such as nutrients, e.g. lipids, (especially triglycerides and

phospholipids, typically of plant or marine animal origin), vitamins, minerals, and folic acid, pH modifiers, viscosity modifiers, flavours, aromas, sweeteners, colorants, antioxidants, etc..

The gelled emulsion compositions of the invention will preferably be in dose unit form, with each dose unit having a weight of 50 to 3000 mg, especially 100 to 1500 mg, particularly 400 to 1000 mg.

The dose units of the gelled emulsion may be formed for example by moulding, extrusion or cutting or the like. For adult use, the dose units are preferably in tablet or lozenge form; however for child use they may conveniently be presented in child- friendly form, e.g. geometric shapes such as rods, strips and tubes, or animal, doll, or vehicle shapes, for example the shape of a popular cartoon character.

The composition of the invention will preferably be uncoated, i.e. not within a capsule or shell-coating. Accordingly, to avoid water loss during storage, the dose units will conveniently be individually packaged, e.g. in foil wrappers or in the blisters of a blister pack. he-oil-phase-of he-oiUinrwate ^ tolerable lipid, e.g. fatty acid esters such as triglycerides and phospholipids, for example plant or animal oils, especially plant and marine animal oils. Particularly preferably an oil is used which is high in omega-3, omega-6 or omega-9 essential fatty acids, especially omega-3 essential fatty acids, more especially EPA and DHA. In this way the oil phase itself is a highly bioavailable source of nutrient lipids.

Examples of omega-3 acids include a-linolenic acid (ALA), stearidonic acid (SDA), eicosatrienoic acid (ETE), eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA),

tetracosapentaenoic acid and tetracosahexaenoic acid. Examples of omega-6 acids include linoleic acid, gamma-linolenic acid, eicosadienoic acid, dihomo- gamma-linolenic acid (DGLA), arachidonic acid (AA), docosadienoic acid, adrenic acid, docosapentaenoic acid, and calendic acid. Examples of omega-9 acids include oleic acid, eicosenoic acid, mead acid, erucic acid and nervonic acid.

It is particularly preferred that the compositions according to the invention contain a citrus flavour (e.g. orange or lemon oil) in order to mask any remaining oil taste on chewing. It is also particularly preferred that the compositions according to the invention contain xylitol, e.g. as 0.5 to 50% wt., preferably 1 to 40% wt., e.g. 15 to 40% wt., in order to mask both taste and mouth feel. These may be in the aqueous phase or the oil phase (e.g. as a water-in-oil-in water emulsion), or both; however inclusion in the aqueous phase will generally be sufficient.

Other than the drug substance, the essential fatty acids may form part or the whole of the oil phase in the gelled emulsion, preferably at least 10% wt, more especially at least 50% wt, particularly at least 80% wt. of that phase. They may be used as single compounds or as compound mixtures, e.g. plant or marine oils.

The oil phase of the oil-in-water emulsion may also contain solubilisers in order to increase the solubility of the drug substance in the oil phase. Suitable solubilisers would be known to a person skilled in the art and include Chremophor EL™, castor oil, Tween 80™, Solutol™ HS15, Lutrol™ and Olestra.

The.aqueous phase of the gelled emulsion will contain water and a physiologically tolerable gelling agent, e.g. a hydrocolloid such as gelatin, alginate, carrageenan or a pectin. Such gelling agents and their gel-forming properties are well known. See for example Phillips GO and Williams PA (Eds.) Handbook of ydrocolloids, Woodhead Publishing, Cambridge (2000). The use of gelatin is especially preferred. Besides water and the gelling agent, the aqueous phase of the gelled emulsion may contain other water-soluble components, e.g. vitamins, minerals, pH modifiers, viscosity modifiers, antioxidants, colorants, flavours, water-soluble drug substances, etc. as desired.

The weight ratio of the lipid phase to the aqueous phase in the gelled emulsions is preferably 1 :19 to 3:1 , especially 35:65 to 1 :1 , particularly 2:3 to 1 :1. Emulsion formation may be effected by conventional techniques; however emulsification under a non-oxidising gas, e.g. nitrogen, is preferred. Likewise, the components of the emulsion are preferably degassed before emulsification and handling and packaging of the set emulsion is preferably performed under such a gas.

The gelled emulsions of and used according to the invention may be produced as described in WO 2007/085835 and WO 2007/085840 and PCT/GB2009/002404 and PCT/GB2009/002406 (copies of which are annexed to the description of this application as Annexes A and B) the contents of which are hereby incorporated by reference.

The gelled emulsions may if desired be more than biphasic. Thus a water-in-oil emulsion may be emulsified with an aqueous gelling agent phase to produce a water-in-oil-in-water double emulsion, or two oil-in-water emulsions with different oil phases may be combined and intimately mixed before gelling onset.

The invention will now be illustrated further with reference to the following non- limiting Examples.

Example 1

-Chewable-emulsion_

Aqueous phase:

Gelatin: 10% wt.

Xylitol: 36% wt

Sorbitol: 14% wt.

Lemon flavour: 0.15% wt.

Yellow colour: 0.1% wt.

50% citric acid: 1% wt

Water: to 100% wt.

The gelatin is added to the water and allowed to swell for 30 min. The gelatin solution is then heated to 70°C under continuous stirring for 45 min. The xylitol and sorbitol is then added to the solution and allowed to dissolve under stirring for 30-60 min. The acid, flavour and colour are then added while stirring. The temperature is lowered to 50°C the solution is mixed for 30 min before stirring is stopped and the solution is left for 30 min.

Marine oil (e.g. commercially available fish liver oil) is mixed with 0.15% wt. lemon flavour.

The marine oil and the aqueous solution are emulsified in a weight ratio of 1:2 at 40-45°C using an ultra turrax. The resultant emulsion is degassed under vacuum to remove air bubbles. When the emulsion is smooth, soft cores are produced by moulding and left to gel for 60 min at 22°C. The cores are dried to reduce the content of water to approximately 10% wt.

Example 2

Drug-containing Compositions

The drugs listed in Table 1 above are dissolved or dispersed in the oil or water phases used in Example 1 (in the oil phase if lipophilic or in the aqueous phase if not) at the concentrations per dose unit set out in Table 1 before emulsions are produced, poured and allowed to set as in Example 1.

For drug concentrations below 100 mg per dose unit, the dose units are

conveniently 250, 500 or 750 mg. For concentrations above 100 mg per dose unit, the dose units are conveniently 500, 1000, 1500, 2000, 2500 or 3000 mg. Where an omega-3 ester is used as the oil of the oil phase, the dose units are preferably at least 1000 mg.

Example 3

Gum arabicum-containing compositions

An aqueous phase is prepared using the following components:

Gelatin 5.7 % wt

Xylitol 24.2 % wt

Sorbitol 10.4 % wt

50% Citric acid 0.6 % wt

Lemon flavour 1.1 % wt

Gum arabicum 3.7 % wt

Water ad 100 % wt Drug-free and drug-containing dose units are prepared using this aqueous phase analogously to Examples 1 and 2.

Example 4

Blister packs

The emulsion dose units of Examples 1 , 2 and 3 are filled into plastic blister pack trays over which a plastic/metal foil laminate is heat sealed.

Example 5

Chewable strips

Before setting, the emulsions of Examples 1, 2 and 3 are extruded into strips which are then sealed into individual plastic/metal foil laminate envelopes.

Example 6

Levoceterizine 5 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

— Citric-acid- _9_mg__

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Levoceterizine 5 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and levoceterizine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet. Example 7

Desloratadin 5 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Desloratadin 5 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and desloratadin are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 8

Naproxen 150 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Naproxen 150 mg Water to 1500 mg

^* Total no more than 600mg

The oil(s) and naproxen are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 9

Phenylephrine 10 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil* 0 - 600 mg

Fish oil^* 0 - 600 mg

Phenylephrine 10 mg

Water to 1500 mq

^* Total no more than 600mg

The oil(s) and phenylephrine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a

metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 10

Pseudoephedrine 120 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Pseudoephedrine 120 mg

Water to 500 mg

^* Total no more than 600mg

The oil(s) and pseudoephedrine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a

Example 11

Aspirin 200 mg

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

-Xylitol— _36^Q-mg_

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Aspirin 200 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and aspirine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet. Example 12

AcetaminoDhene 200 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Acetaminophen 200 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and acetaminophen are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally -5ealed-with-a-metal plasticsJoiLco_v.er_sbe.eL

Example 13

Ibuorofen 200 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg Ibuprofene 200 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and ibuprofene are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 14

Guaifenesin 100 mg

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

-Fish-oil^*- - ._0.----6.0.0_mg_

Guaifenesin 100 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and guaifenesen are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 15

Dextromethorphan 15 mg

Components

Gelatin 84 mg Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Dextromethrophan 15 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and dextromethrophan are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 16

Brompheniramine 4 mg

Components

Gelatin 84 mg

-Gum-arabicum 55.5_mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil* 0 - 600 mg

Fish oil* 0 - 600 mg

Brompheniramine 4 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and brompheniramine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 17

Diphenhydramine 25 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil* 0 - 600 mg

Diphenhydramine 25 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and diphenhydramine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a

-metal/plasticsJaminate_^blisterJr_.ay_aDd_alIowed_to^et. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 18

Chlorpheniramine 4 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil* 0 - 600 mg Fish oil^* 0 - 600 mg

Chlorpheniramine 4 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and chlorpheniramine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 19

Clemastine 2 mq

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fi h oil^* 0 - 600 mg

Clemastine 2 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and clemastine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 20

Loratadine 10 mg

Components

Gelatin 84 mg Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Loratadine 10 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and loratadine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 21

Combination gel of dextromethorphan, phenylephrine and chlorpheniramine Components

Gelatin 84 mg

-Gum-arabicum-- 55.5-.mg_

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Dextromethorphan 15 mg

Phenylephrine 10 mg

Chlorpheniramine 3 mg

Water to 1500 mg

* Total no more than 600mg The oil(s) and dextromethorphan, phenylephrine and chlorpheniramine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 22

Combination gel of dextromethorphan, guaifenesin and pseudoephedrine

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil* 0 - 600 mg

Fish oil* 0 - 600 mg

Dextromethorphan 15 mg

Guaifenesin 200 mg

Pseudoephedrine 30 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and dextromethorphan, guaifenesin and pseudoephedrine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 23

Combination gel of Acetaminophen. Diphenhydramine and Phenylephrine

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Acetaminophen 150 mg

Diphenhydramine 10 mg

Phenylephrine 5 mg

Water to 1500 mg

^* Total no more than 600mg

The oil(s) and acetaminophen, diphenhydramine and phenylephrine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 24

Combination gel of Diphenhydramine and Phenylephrine

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

_S-or.bj.taL. _JJ_5jrig

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil* 0 - 600 mg

Fish oil^* 0 - 600 mg

Diphenhydramine 25 mg

Phenylephrine 5 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and diphenhydramine and phenylephrine are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Example 25

Combination ael of Brompheniramine maleate. Phenylpropanolamine hydrochloride and Codeine phosphate

Components

Gelatin 84 mg

Gum arabicum 55.5 mg

Sorbitol 155 mg

Xylitol 360 mg

Citric acid 9 mg

Flavour 18 mg

Colour 10.5 mg

Plant oil^* 0 - 600 mg

Fish oil^* 0 - 600 mg

Brompheniramine maleate 2 mg

Phenylpropanolamine hydrochloride 12.5 mg

Codeine phosphate 10 mg

Water to 1500 mg

* Total no more than 600mg

The oil(s) and brompheniramine maleate, phenylpropanolamine hydrochloride and codeine phosphate are emulsified with the aqueous phase and the emulsion is poured in aliquots of 1.5 g into elongate moulds lined with a metal/plastics laminate blister tray and allowed to set. The blister tray is thermally sealed with a metal/plastics foil cover sheet.

Claims

Claims:

1. An oral pharmaceutical composition comprising an over the counter drug substance contained in a physiologically tolerable gelled oil-in-water emulsion.

2. A pharmaceutical composition, comprising a drug substance contained in a physiologically tolerable gelled oil-in-water emulsion, wherein said drug substance is an over the counter drug substance for use in medicine.

3. A pharmaceutical composition, comprising a drug substance contained in a physiologically tolerable gelled oil-in-water emulsion, wherein said drug substance is an over the counter drug substance for use treatment to combat pain (e.g.

headaches), allergies (e.g. itchy eyes/nose/throat, sneezing), coughs and colds, fever, runny noses, congestions, hoarseness, or sore throats.

4. Use of an over the counter drug substance contained in a physiologically tolerable gelled oil-in-water emulsion for the manufacture of a medicament for use by oral administration in the treatment of pain (e.g. headaches), allergies (e.g. itchy eyes/nose/throat, sneezing), coughs and colds, fever, runny noses, congestions, hoarseness, or sore throats. 5 A methojl )iJj¾ iljent pfj nujrnan subject to combat pain (g.g^ headaches), allergies (e.g. itchy eyes/noses/throat, sneezing), coughs and colds, fever, runny noses, congestions, hoarseness, or sore throats which method comprises orally administering to said subject an effective amount of a provides a pharmaceutical composition, comprising a drug substance contained in a physiologically tolerable gelled oil-in-water emulsion, wherein said drug substance is an over the counter drug substance.