Pharmaceutical formulations

Abstract

A textured gel formation capable of formulating an Active Pharmaceutical Ingredient (API) of Biopharmaceutics Classification System (BCS) class I, II or III. The formulation comprises a BCS class I, I

Description

[0001] This invention relates to pharmaceutical formulations and more particularly to one for an Active Pharmaceutical Ingredient (API) which is recognised under the Biopharmaceutics Classification System (BCS) as a Class I, Class II or Class III drug. BACKGROUND

[0002] APIs can be difficult to formulate as their properties differ from API to API. Two of the parameters that challenge a formulation chemist are an APIs solubility and its permeability. Accordingly, APIs are broadly defined as those falling into one of four classification types based on these two parameters. These four types are illustrated in Fig 1.

[0003] Class I APIs have high permeability and high solubility. a. An Example is Metoprolol. b. Class I compounds are well absorbed, and their absorption rate is usually higher than excretion.

[0004] Class II APIs have high permeability and low solubility. a. Examples include Ibuprofen and Naproxen. b. The bioavailability of those products is limited by their solvation rate. A correlation between the in vivo bioavailability and the in vitro solvation can be found.

[0005] Class III APIs have low permeability and high solubility. a. An example is Cimetidine. b. The absorption is limited by the permeation rate, but the drug is solvated very fast. If the formulation does not change the permeability or gastro-intestinal duration time, then class I criteria can be applied.

[0006] Class IV APIs have low permeability and low solubility. a. An example is Bifonazole. b. These compounds have a poor bioavailability. Usually, they are not well absorbed over the intestinal mucosa and a high variability is expected.

[0007] The APIs are classified in BCS on the basis of solubility, permeability, and also dissolution.

[0008] Solubility class boundaries are based on the highest dose strength of an immediate release product. A drug is considered highly soluble when the highest dose strength is soluble in 250 ml or less of aqueous media over the pH range of 1 to 7.5. The volume estimate of 250 ml is derived from typical bioequivalence study protocols that prescribe administration of a drug product to fasting human volunteers with a glass of water.

[0009] Permeability class boundaries are based indirectly on the extent of absorption of a drug substance in humans and directly on the measurement of rates of mass transfer across human intestinal membrane. Alternatively non-human systems capable of predicting drug absorption in humans can be used (such as in-vitro culture methods). A drug substance is considered highly permeable when the extent of absorption in humans is determined to be 90% or more of the administered dose based on a mass-balance determination or in comparison to an intravenous dose.

[0010] Dissolution class boundaries include an immediate release product, namely one which is rapidly dissolving, i.e. when no less than 85% of the labelled amount of the drug substance dissolves within 15 minutes using USP Dissolution Apparatus 1 at 100 RPM or Apparatus 2 at 50 RPM in a volume of 900 ml or less in the following media: 0.1 M HCI or simulated gastric fluid or pH 4.5 buffer and pH 6.8 buffer or simulated intestinal fluid.

[0011] Most oral formulations take the form of filled capsules or tablets. There is therefore a need to provide alternative dosage forms of many drugs, which dosage forms can be more readily taken by certain patient groups e.g. children, and the elderly.

[0012] Having a “base” formulation which is suitable for a number of different APIs would be advantageous in that it lowers regulatory hurdles and reduce costs in bringing “equivalents” to market.

[0013] Of course, other formulation types are known, and Applicant has developed several drinkable gel-based formulations in areas such as glucose tolerance testing and for delivering nutraceuticals - see respectively: WO2017 / 075672, WO2019215641, WO2024028788 and WO2024134616.

[0014] However, there remains a need to develop pharmaceutical formulations which are easier to swallow or have other benefits e.g. improved shelf life, bioavailability, taste and / or texture.

[0015] In this regard Applicant has also developed a “base formulation” for BCS class II drugs - application number PCT / IB2024 / 054921, but it remains desirable to be able to formulate other BCS class drugs using a common approach rather than having many bespoke formulations.

[0016] It is an object of the present invention to provide alternative pharmaceutical formulations for difficult to formulate drugs, whether BCS Class I drugs, as exemplified by, for example, (1) Cetirizine, a Class II drug as exemplified by, for example, (2) Ibuprofen or a Class III drug as exemplified by, for example (3) Metformin.

[0017] Cetirizine is a second generation anti-histamine, see

[0018] Branded versions include Allacan, Piriteze, and Zyrtec.

[0019] Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation, see https: / / en.wikipecjja.o

[0020] Branded versions include Advil, Motrin and Nurofen.

[0021] Metformin is the main first-line medication for the treatment of Type 2 diabetes, see https: / 7en.wikipedia.org / wiki / Metformin.

[0022] Branded versions include Glucophage, Riomet, Fortamet, and Glumetza in the US and Obimet, Gluformin, Dianben, Diabex, Diaformin, Metsol, Siofor, Metfogamma and Glifor in other parts of the world.

[0023] From a regulatory perspective it is possible to obtain registration for a new dosage form using an abridged process such as that provided by the FDA using 505(B)(2) regulatory pathways. See for example: https: / / www.fda.gov / media / 156350 / download incorporated by reference. BRIEF SUMMARY OF THE DISCLOSURE

[0024] In accordance with the present inventions there is provided a textured gel formulation capable of formulating Active Pharmaceutical Ingredient (API) spanning Biopharmaceutics Classification System (BCS) class I, II and III comprising: i) a Biopharmaceutics Classification System (BCS) class I, II or III Active Pharmaceutical Ingredient (API), or a salt or solution thereof, ii) a primary gelling agent which is a carrageenan, iii) a first secondary gelling agents which is an alginate, iv) a second secondary gelling agent which is an agar, v) at least one cation donator, vi) a preservative, vii) at least one pH modifier, and viii) water.

[0025] In some embodiments the formulation further comprises one or more of: ix) one or more sweetener(s), x) an emulsifier, xi) an oil, and xii) a flavouring.

[0026] Non-limiting examples of textured formulations comprising APIs representative of different BCS classes include (by LISAN naming) Cetirizine (a BCS class I API), or a salt or solution thereof, Ibuprofen (a BCS class II API), or a salt or solution thereof, and Metformin (a BCS class III API), or a salt or solution thereof.

[0027] United States Adopted Name (USAN) is a non-proprietary name for a pharmaceutical drug that is assigned by the USAN Council. The same drug may appear under different brand names.

[0028] The terms “primary”, and “secondary” are used to denote the relative proportion (by weight percent) of the respective gelling agents such that the primary gelling agent (carrageenan) is present in the greatest amount and at least two secondary gelling agents (agar and alginate) are present in a lesser amount.

[0029] The at least two secondary gelling agents are present such that either can be present in an amount which is greater, lesser or equal to the other.

[0030] The primary agent is a carrageenan, more particularly kappa carrageenan.

[0031] Carrageenan’s are large, highly flexible molecules that form curling helical structures. This gives them the ability to form a variety of different gels at room temperature. They are widely used in the food and other industries as thickening and stabilizing agents.

[0032] All carrageenan’s are high-molecular-weight polysaccharides and are mainly made up of alternating 3-linked p-D-galactopyranose (G-units) and 4-linked a-D-galactopyranose (D-units) or 4-linked 3,6-anhydro-a-D-galactopyranose (DA-units), forming the disaccharide repeating unit of carrageenan’s.

[0033] There are three main commercial classes of carrageenan: • Kappa which forms strong, rigid gels in the presence of sodium and potassium ions. • lota which forms soft gels in the presence of calcium ions, and ® Lambda which does not gel.

[0034] The secondary gelling agents are alginate and agar.

[0035] The alginates include: • Sodium alginate (NaCsHyOs), • Potassium alginate (KCsHyOs), and • Calcium alginate (CaC^H^CM.

[0036] Agar is an elastic, as opposed to plastic gel.

[0037] Agar is outstanding among hydrocolloids. Agar-agar gels can be formed in very dilute solutions, containing as little as 0.5% to 1.0% of agar-agar. These gels are rigid, brittle, have well defined shapes, as well as sharp melting and gelling points. Moreover, they clearly demonstrate the interesting phenomenon of syneresis (spontaneous extrusion of water through the surface of the gel), and hysteresis (temperature interval between melting and gelling temperatures). Gelling occurs at temperatures far below the gel melting temperature. A 1.5% solution of agar-agar forms a gel on cooling to about 32° to 45° C that does not melt below 85° C. This hysteresis interval is a novel property of agar-agar that finds many uses in food applications. The gel strength of the agar-agar is influenced by concentration, time, pH, and sugar content. The pH noticeably affects the strength of the agar gel; as the pH decreases, the gel strength weakens. Sugar content also has a considerable effect over agar gel. Increasing levels of sugar make gels with harder but a less cohesive texture.

[0038] Following extensive studies Applicant determined not only were three specific gelling agents required, but it was necessary to control their relative amounts.

[0039] The three gelling agents may broadly be used in the relative proportions (by weight) in a ratio, relative to the alginate, of from: ii) carrageenan greater than 1.0 to 6.2, iv) agar 0.2 to 2.1, and iii) alginate 1.0 with the proviso that the carrageenan is present in the greatest amount.

[0040] The three gelling agents are optimally used in the relative proportions (by weight) in a ratio, relative to the alginate, of from: ii) carrageenan - 1.6 to 4.8, iv) agar - 0.5 to 1.5, and iii) alginate - 1.0. with the proviso that the carrageenan is present in the greatest amount.

[0041] Broadly the carrageenan is present in an amount, by weight %, of from 0.13 to 0.53, the agar is present in an amount, by weight %, of from 0.02 to 0.18, and the alginate is present in an amount, by weight %, of from 0.05 to 0.16 with the proviso that the carrageenan is present in the greatest amount.

[0042] More preferably still the carrageenan is present in an amount, by weight %, of from 0.20 to 0.41, the agar is present in an amount, by weight %, of from 0.06 to 0.13. and the alginate is present in an amount, by weight %, of from 0.05 to 0.16 with the proviso that the carrageenan is present in the greatest amount.

[0043] The preferred carrageenan is kappa carrageenan, the preferred agar is agar-agar, and the preferred alginate is sodium alginate.

[0044] To facilitate gelling of the alginate the cation donator comprises a divalent cation which facilitates cross linking of the alginate.

[0045] Preferably the v) at least one divalent cation is a calcium or magnesium cation, offered as a salt.

[0046] In a preferred embodiment the v) cation donator is magnesium chloride.

[0047] The ratio of alginate (present and measured as the weight of the salt) to the divalent cation (present and measured as the weight of the salt) is from 1.5:1 to 6:1.

[0048] The amount, by weight %, of the divalent cation (present as the salt) is from 0.03 to 0.06.

[0049] Preferably the vi) at least one preservative is selected from lactic acid, potassium sorbate, sorbic acid and sodium benzoate.

[0050] In a preferred embodiment the preservative is potassium sorbate.

[0051] Preferably the vii) at least one pH modifier is an acidifying agent, alkalizing agent (base) or buffering agent depending on the API. Exemplary modifiers include: acetic acid, citric acid, hydrochloric acid, malic acid, phosphoric acid and sodium hydroxide.

[0052] The pH is in general controlled to be between 4.0 and 7.5.

[0053] It varies for the API with the favoured pH for the exemplary APIs being: • Cetirizine pH 4.2 to 5.2, preferably 4.7 • Ibuprofen pH 6.4 to 7.4, preferably 6.9 and • Metformin pH 4.5 to 5.5, preferably 5.0

[0054] In some embodiments it is desirable to include ix) at least one sweetener.

[0055] A preferred sweetener is sucralose and I or sorbitol.

[0056] In some embodiments it is desirable to include x) an emulsifier

[0057] A preferred emulsifier is lecithin.

[0058] In some embodiments it is desirable to include xi) an oil.

[0059] A preferred oil is sunflower oil.

[0060] In some embodiments it is desirable to include xii) a flavouring

[0061] Preferred flavourings include fruit flavours or menthol.

[0062] With respect to the weight percent figures, for “generic” claims these are based on the essential components specified and exclude optional excipients. However, for specific drug formulations they include all identified excipients.

[0063] The actual amounts vary with the particular API selected.

[0064] In a first embodiment the API is Cetirizine or a salt or solution thereof.

[0065] Preferably the salt is a hydrochloride.

[0066] The Cetirizine formulation comprises ingredients (by weight %) in the range as set out in Table 1a. Table 1a Active / Excipient Min % Max % viii) Water 65.00 to 100.00 vii) pH modifier(s) 0.08 0.50 i) Cetirizine Dihydrochloride 0.02 0.06 vi) Preservative 0.04 0.20 v) Divalent Cation 0.02 0.06 v) Monovalent Cation 0.01 0.03 iv) Agar 0.06 0.20 ii) Carrageenan 0.20 0.50 iii) Sodium Alginate 0.09 0.20 xii) Flavouring 0.06 0.20 ix) Sweetener(s) 0.00 10.00

[0067] More preferably the formulation comprises ingredients (by weight %) in the range as set out in Table 1b. Table 1b Active / Excipient Min % Max % viii) Water 64.01 to 100.00 vii) Citric Acid 0.08 0.14 vii) Sodium Citrate 0.22 0.41 i) Cetirizine Dihydrochloride 0.03 0.05 vi) Potassium Sorbate 0.06 0.12 v) Magnesium Chloride 0.03 0.05 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.07 0.12 ii) Kappa Carrageenan 0.20 0.38 iii) Sodium Alginate 0.09 0.16 xii) Flavouring 0.06 0.12 ix) Sucralose 0.01 0.02 ix) Sorbitol 0.00 9.51 5

[0068] Most preferably still the formulation comprises ingredients (by weight (g) or weight %) as set out in Table 1c and 1d and has a pH of 4.7. Table 1c Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 98.67 vii) Citric Acid 0.03 0.12 vii) Sodium Citrate 0.09 0.34 i) Cetirizine Dihydrochloride 0.01 0.04 vi) Potassium Sorbate 0.03 0.10 v) Magnesium Chloride 0.01 0.04 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.32 iii) Sodium Alginate 0.03 0.14 xii) Flavouring - Menthol 0.03 0.10 ix) Sucralose 0.01 0.02 Total 25.34 100.00 Table 1d Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 91.45 vii) Citric Acid 0.03 0.11 vii) Sodium Citrate 0.09 0.32 i) Cetirizine Dihydrochloride 0.01 0.04 vi) Potassium Sorbate 0.03 0.09 v) Magnesium Chloride 0.01 0.04 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.03 0.09 ii) Kappa Carrageenan 0.08 0.29 iii) Sodium Alginate 0.03 0.13 xii) Flavouring - Blood Orange or Grape 0.03 0.09 ix) Sucralose 0.01 0.02 ix) Sorbitol 2.00 7.32 Total 27.34 100.00

[0069] In a second embodiment the API is Ibuprofen or a salt or solution thereof.

[0070] The Ibuprofen formulation comprises ingredients (by weight %) in the range as set out in Table 2a Table 2a 5 Active / Excipient Min % Max % viii) Water 65.00 to 100.00 i) Ibuprofen Sodium 0.60 1.40 vi) Preservative 0.01 0.20 v) Divalent Cation 0.02 0.07 v) Monovalent Cation 0.01 0.04 vii) pH modifier(s) 0.05 0.70 iv) Agar 0.05 0.20 ii) Carrageenan 0.10 0.45 iii) Alginate 0.04 0.20

[0071] More preferably the formulation comprises ingredients (by weight %) in the range as set out in Table 2b. Table 2b Active / Excipient Min % Max % viii) Water 68.44 to 100.00 i) Ibuprofen Sodium 0.70 1.30 vi) Potassium sorbate 0.07 0.13 v) Magnesium chloride 0.03 0.06 v) Potassium chloride 0.01 0.03 vii) Sodium bicarbonate 0.34 0.64 vii) Citric acid 0.06 0.11 iv) Agar 0.07 0.13 ii) Kappa Carrageenan 0.22 0.41 iii) Sodium alginate 0.06 0.11 10

[0072] In a third embodiment the API is Metformin or a salt or solution thereof.

[0073] Most preferably still the formulation comprises ingredients (by weight (g) or weight %) as set out in Table 2c and has a pH of 6.9. Table 2c Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 97.77 i) Ibuprofen Sodium 0.26 1.00 vi) Potassium sorbate 0.03 0.10 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Sodium bicarbonate 0.13 0.49 vii) Citric acid 0.02 0.08 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.31 iii) Sodium alginate 0.02 0.08 Total 25.57 100.00

[0074] The Metformin formulation comprises ingredients (by weight %) in the range as 5 set out in Table 3a. Table 3a Active / Excipient Min % Max % viii) Water 55.00 to 100.00 vi) Preservative 0.05 0.15 v) Divalent cation 0.02 0.06 v) Monovalent cation 0.01 0.03 vii) pH modifier 0.04 0.40 iv) Agar 0.04 0.40 ii) Carrageenan 0.15 1.20 iii) Alginate 0.04 0.35 ix) Sweetener 0.00 10.00 xi) Oil 0.05 4.00 x) Emulsifier 0.20 0.60 i) Metformin hydrochloride 0.03 4.00 xii) Flavouring 0.10 0.85

[0075] More preferably the formulation comprises ingredients (by weight %) in the range as set out in Table 3b. Table 3b Active / Excipient Min % Max % viii) Water 62.63 to 100.00 vi) Potassium sorbate 0.06 0.12 v) Magnesium chloride 0.03 0.05 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.05 0.10 iv) Agar 0.06 0.12 ii) Kappa Carrageenan 0.20 0.37 iii) Sodium alginate 0.05 0.10 ix) Sweetener 0.00 9.30 xi) Sunflower Oil 0.25 0.47 x) Lecithin 0.25 0.47 i) Metformin hydrochloride 1.25 2.33 xii) Flavouring 0.13 0.23 ix) Sucralose 0.01 0.02

[0076] Most preferably still the formulation comprises ingredients (by weight (g) or weight %) as set out in Table 3c and Table 3d and has a pH of 5.0. Table 3c Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 94.54 vi) Potassium sorbate 0.03 0.09 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.02 0.08 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.30 iii) Sodium alginate 0.02 0.08 xi) Sunflower Oil 0.10 0.38 x) Lecithin 0.10 0.38 i) Metformin hydrochloride 1.00 3.78 xii) Flavouring - Menthol 0.05 0.19 ix) Sucralose 0.01 0.02 Total 26.44 100.00 5 Table 3d Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 87.89 vi) Potassium sorbate 0.03 0.09 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.02 0.07 iv) Agar 0.03 0.09 ii) Kappa Carrageenan 0.08 0.28 iii) Sodium alginate 0.02 0.08 ix) Sorbitol 2.00 7.03 xi) Sunflower Oil 0.10 0.35 x) Lecithin 0.10 0.35 i) Metformin hydrochloride 1.00 3.52 xii) Flavouring - Blood Orange or Grape 0.05 0.18 ix) Sucralose 0.01 0.02 Total 28.44 100.00

[0077] The invention is further described, by way of example only, with reference to the drawing, Examples and detailed description given below. BRIEF DESCRIPTION OF THE DRAWINGS

[0078] Embodiments of the invention are further described hereinafter with reference to the accompanying drawing, in which: Fig 1 is a diagram illustrating the Biopharmaceutics Classification System (BCS). DETAILED DESCRIPTION

[0079] In developing a generic formulation for BCS class I, II and III APIs, Applicant undertook a series of experiments and overcame a number of technical challenges.

[0080] For ease of following, set out below are a series of Examples, for an exemplary BCS class I, II and III drug, followed by some comparative Examples which highlight some of the technical challenges overcome.

[0081] Each of the Examples was prepared using the methodology set out below: Method

[0082] Add the API (e.g. Cetirizine, Ibuprofen or Metformin), magnesium chloride, potassium chloride, and potassium sorbate to a beaker. Where applicable, add sweeteners sucralose and sorbitol, and flavouring. Add water and mix until dissolved. Measure the pH of the solution and pH adjust using citric acid, sodium citrate and I or sodium bicarbonate, where required. Using a stirring hot plate, heat the solution to 95°C to 100°C. Once the temperature has reached 95°C or above, slowly add the gelling agents (e.g. kappa carrageenan, agar and sodium alginate) and mix until completely dissolved. Finally, add the flavouring and mix until dissolved. Hot fill the gel into the pouch and cap immediately. Let cool to room temperature. Pouches may require air to inflate the pouch prior to filling. Where an emulsion is required, see e.g. Metformin Example the water is split and the emulsion mixed with the other components. EXAMPLE 1

[0083] The drug Cetirizine was formulated, and the gelling agents were found to provide a satisfactory product when the ingredients were present in amounts (weight %) as illustrated in Table 1a below: Table 1a Active / Excipient Min % Max % viii) Water 65.00 to 100.00 vii) pH modifier(s) 0.08 0.50 i) Cetirizine Dihydrochloride 0.02 0.06 vi) Preservative 0.04 0.20 v) Divalent Cation 0.02 0.06 v) Monovalent Cation 0.01 0.03 iv) Agar 0.06 0.20 ii) Carrageenan 0.20 0.50 iii) Sodium Alginate 0.09 0.20 xii) Flavouring 0.06 0.20 ix) Sweetener(s) 0.00 10.00 5

[0084] A preferred product was obtained when the ingredients were present in amounts (weight %) as illustrated in Table 1b below: Table 1b Active / Excipient Min % Max % viii) Water 64.01 to 100.00 vii) Citric Acid 0.08 0.14 vii) Sodium Citrate 0.22 0.41 i) Cetirizine Dihydrochloride 0.03 0.05 vi) Potassium Sorbate 0.06 0.12 v) Magnesium Chloride 0.03 0.05 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.07 0.12 ii) Kappa Carrageenan 0.20 0.38 iii) Sodium Alginate 0.09 0.16 xii) Flavouring 0.06 0.12 ix) Sucralose 0.01 0.02 ix) Sorbitol 0.00 9.51

[0085] An optimum product was obtained when the ingredients were present in amounts by weight or weight % as illustrated in Table 1c and 1d below with a pH of 4.7. Table 1c Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 98.67 vii) Citric Acid 0.03 0.12 vii) Sodium Citrate 0.09 0.34 i) Cetirizine Dihydrochloride 0.01 0.04 vi) Potassium Sorbate 0.03 0.10 v) Magnesium Chloride 0.01 0.04 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.32 iii) Sodium Alginate 0.03 0.14 xii) Flavouring - Menthol 0.03 0.10 ix) Sucralose 0.01 0.02 Total 25.34 100.00 Table 1d Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 91.45 vii) Citric Acid 0.03 0.11 vii) Sodium Citrate 0.09 0.32 i) Cetirizine Dihydrochloride 0.01 0.04 vi) Potassium Sorbate 0.03 0.09 v) Magnesium Chloride 0.01 0.04 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.03 0.09 ii) Kappa Carrageenan 0.08 0.29 iii) Sodium Alginate 0.03 0.13 xii) Flavouring - Blood Orange or Grape 0.03 0.09 ix) Sucralose 0.01 0.02 ix) Sorbitol 2.00 7.32 Total 27.34 100.00 EXAMPLE 2 5

[0086] The drug Ibuprofen was formulated, and the gelling agents were found to provide a satisfactory product when the ingredients were present in amounts (weight %) as illustrated in Table 2a below: Table 2a Active / Excipient Min % Max % viii) Water 65.00 to 100.00 i) Ibuprofen Sodium 0.60 1.40 vi) Preservative 0.01 0.20 v) Divalent Cation 0.02 0.07 v) Monovalent Cation 0.01 0.04 vii) pH modifier(s) 0.05 0.70 iv) Agar 0.05 0.20 ii) Carrageenan 0.10 0.45 iii) Alginate 0.04 0.20

[0087] A preferred product was obtained when the ingredients were present in amounts (weight %) as illustrated in Table 2b below: Table 2b Active / Excipient Min % Max % viii) Water 68.44 to 100.00 i) Ibuprofen Sodium 0.70 1.30 vi) Potassium sorbate 0.07 0.13 v) Magnesium chloride 0.03 0.06 v) Potassium chloride 0.01 0.03 vii) Sodium bicarbonate 0.34 0.64 vii) Citric acid 0.06 0.11 iv) Agar 0.07 0.13 ii) Kappa Carrageenan 0.22 0.41 iii) Sodium alginate 0.06 0.11

[0088] An optimum product was obtained when the ingredients were present in amounts 5 by weight or weight % as illustrated in Table 2c below with a pH of 6.9: Table 2c Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 97.77 i) Ibuprofen Sodium 0.26 1.00 vi) Potassium sorbate 0.03 0.10 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Sodium bicarbonate 0.13 0.49 vii) Citric acid 0.02 0.08 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.31 iii) Sodium alginate 0.02 0.08 Total 25.57 100.00 EXAMPLE 3

[0089] The drug Metformin was formulated, and the gelling agents were found to provide 10 a satisfactory product when the ingredients were present in amounts (weight %) as illustrated in Table 3a below: Table 3a Active / Excipient Min % Max % viii) Water 55.00 to 100.00 vi) Preservative 0.05 0.15 v) Divalent cation 0.02 0.06 v) Monovalent cation 0.01 0.03 vii) pH modifier 0.04 0.40 iv) Agar 0.04 0.40 ii) Carrageenan 0.15 1.20 iii) Alginate 0.04 0.35 ix) Sweetener 0.00 10.00 xi) Oil 0.05 4.00 x) Emulsifier 0.20 0.60 i) Metformin hydrochloride 0.03 4.00 xii) Flavouring 0.10 0.85

[0090] A preferred product was obtained when the ingredients were present in amounts (weight %) as illustrated in Table 3b below: Table 3b Active / Excipient Min % Max % viii) Water 62.63 to 100.00 vi) Potassium sorbate 0.06 0.12 v) Magnesium chloride 0.03 0.05 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.05 0.10 iv) Agar 0.06 0.12 ii) Kappa Carrageenan 0.20 0.37 iii) Sodium alginate 0.05 0.10 ix) Sweetener 0.00 9.30 xi) Sunflower Oil 0.25 0.47 x) Lecithin 0.25 0.47 i) Metformin hydrochloride 1.25 2.33 xii) Flavouring 0.13 0.23 ix) Sucralose 0.01 0.02 5

[0091] An optimum product was obtained when the ingredients were present in amounts by weight or weight % as illustrated in Table 3c and 3d below with a pH of 5.0: Table 3c Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 94.54 vi) Potassium sorbate 0.03 0.09 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.02 0.08 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.30 iii) Sodium alginate 0.02 0.08 xi) Sunflower Oil 0.10 0.38 x) Lecithin 0.10 0.38 i) Metformin hydrochloride 1.00 3.78 xii) Flavouring - Menthol 0.05 0.19 ix) Sucralose 0.01 0.02 Total 26.44 100.00 Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 87.89 vi) Potassium sorbate 0.03 0.09 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.02 0.07 iv) Agar 0.03 0.09 ii) Kappa Carrageenan 0.08 0.28 iii) Sodium alginate 0.02 0.08 ix) Sorbitol 2.00 7.03 xi) Sunflower Oil 0.10 0.35 x) Lecithin 0.10 0.35 i) Metformin hydrochloride 1.00 3.52 xii) Flavouring - Blood Orange or Grape 0.05 0.18 ix) Sucralose 0.01 0.02 Total 28.44 100.00 DEVELOPMENT AND COMPARATIVE EXAMPLES 5 Experimental series 1 (BCS class II)

[0092] The ibuprofen gel created in PCT / IB2024 / 054921 had a firm texture and Applicant desired a thinner more drinkable texture.

[0093] Starting from this Ibuprofen formulation, Table 4a, they sought to develop a thinner more drinkable gel. 10 Table 4a Ibuprofen gel (200 mg / 25ml) - pH 6.8 Active / Excipient Mass Unit % i) Ibuprofen 0.20 g 0.78 viii) Water 25.00 g 97.42 vi) Potassium sorbate 0.03 g 0.10 v) Magnesium chloride 0.11 g 0.43 v) Potassium chloride 0.01 g 0.02 iv) Agar 0.15 g 0.58 ii) Kappa carrageenan 0.10 g 0.39 iii) Sodium alginate 0.05 g 0.19 vii) Citric acid 0.02 g 0.08 TOTAL 25.66 g 100.00

[0094] To this end they reduced the original gelling agents: agar, kappa and alginate in the masses 0.15g, 0.10g and 0.05g by (1a) 10%, (1b) 20% and (1c) 25% to observe texture changes - see Table 4b. Table 4b (1a) 10% Reduction (1b) 20% Reduction (1c) 25% Reduction Active / Excipient Mass (g) Percentage (%) Mass (g) Percentage (%) Mass (g) Percentage (%) Ibuprofen sodium 0.26 1.00 0.26 1.00 0.26 1.00 Water 25.00 97.70 25.00 97.77 25.00 97.87 Potassium sorbate 0.03 0.10 0.03 0.10 0.03 0.10 Magnesium chloride 0.01 0.04 0.01 0.04 0.01 0.04 Potassium chloride 0.01 0.02 0.01 0.02 0.01 0.02 Agar 0.14 0.53 0.13 0.50 0 11 0.44 Kappa carrageenan 0.09 0.35 0.08 0.31 0.08 0.29 Sodium alginate 0.05 0.18 0.04 0.17 0.04 0.15 Citric acid 0.02 0.08 0.02 0.08 0.02 0.08

[0095] Gel 1a was still quite firm, gel 1b was semi-firm and gel 1c was soft. Gel 1b -Table 4c was selected for further development.

[0096] Applicant tested 75%, 50% and 25% of the original gelling agents: agar, kappa 10 carrageenan and sodium alginate. The 75% and 50% gel had a firm texture but released water (syneresis) over time, with the 50% gel releasing most. The 25% gel had not set and was too watery. This demonstrated that the reduction of gelling agents was too extreme resulting in the collapsing of the gel. Table 4c Active / Excipient Min % Max% Ibuprofen sodium 1.00 1.01 Water 98.02 98.50 Potassium sorbate 0.10 0.10 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.13 0.38 Kappa carrageenan 0.08 0.24 Sodium alginate 0.04 0.13 Citric acid 0.08 0.08

[0097] Gel strength was investigated by increasing the agar concentration relative to the kappa carrageenan and sodium alginate, which were kept constant. The agar concentration was increased by 20%, 40%, 60% and 80% as illustrated in Table 4d. Table 4d Active / Excipient Min % Max% Ibuprofen sodium 1.01 1.01 Water 98.31 98.46 Potassium sorbate 0.10 0.10 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.05 0.20 Kappa carrageenan 0.16 0.16 Sodium alginate 0.08 0.08 Citric acid 0.08 0.08

[0098] The gel with 40% agar was firm yet soft when mechanically crushed. It had a good texture and was further investigated.

[0099] Applicant then investigated potentially making the Carrageenan the primary gelling agent, with agar the secondary gelling agent - see formulations of Table 4e. 10 Table 4e Active / Excipient Min % Max% Ibuprofen sodium 1.01 1.01 Water 98.15 98.30 Potassium sorbate 0.10 0.10 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.05 0.20 Kappa carrageenan 0.31 0.31 Sodium alginate 0.08 0.08 Citric acid 0.08 0.08

[00100] By doubling the concentration of kappa carrageenan, they obtained a much-improved gel texture. However, pH and flavouring remained a challenge and so sodium bicarbonate was added resulting in a favoured composition - See Table 2c. Experimental series 2 (BCS class I)

[00101] Applicant utilised a base gel based on Ibuprofen gel (Table 2c) for Cetirizine as set out in Table 5a. Table 5a Active / Excipient Mass (g) Percentage (%) i) Cetirizine Dihydrochloride 0.01 0.04 viii) Water 25.00 99.21 vi) Potassium Sorbate 0.03 0.10 v) Magnesium Chloride 0.01 0.04 v) Potassium Chloride 0.01 0.02 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.32 iii) Sodium Alginate 0.02 0.09 vii) Citric Acid 0.02 0.08

[00102] As the pH of the gel was less than 4.0, and the preferred pH range is between 4.0 - 6.0, Applicant looked first to modify the pH. 5

[00103] They investigated both (i) changing the acid source, and (ii) introducing a buffer.

[00104] A change of acid is illustrated in Table 5b Table 5b Active / Excipient Min % Max % Cetirizine Dihydrochloride 0.04 0.04 Water 99.14 99.23 Potassium Sorbate 0.10 0.10 Magnesium Chloride 0.04 0.04 Potassium Chloride 0.02 0.02 Agar 0.10 0.10 Kappa Carrageenan 0.32 0.32 Sodium Alginate 0.09 0.09 Malic Acid 0.10 0.20

[00105] The malic acid tested at ranges 0.1% - 0.2% yielded the same result as citric 10 acid.

[00106] Introducing a buffer (sodium citrate) - also considered a pH control agent proved largely effective at modifying the pH to between 4.5 and 5, but some syneresis was evident with the change in pH - Table 5c. Table 5c Active / Excipient Mass (g) Percentage (%) Cetirizine Dihydrochloride 0.01 0.04 Water 25.00 98.83 Potassium Sorbate 0.03 0.10 Magnesium Chloride 0.01 0.04 Potassium Chloride 0.01 0.02 Agar 0.03 0.10 Kappa Carrageenan 0.08 0.32 Sodium Alginate 0.02 0.08 Citric Acid 0.03 0.12 Sodium Citrate 0.09 0.34

[00107] To address the syneresis of the gel Applicant adjusted the concentration of sodium alginate. They found, unlike for the case of Ibuprofen, where agar was in a slight excess to alginate, the reverse was true - see Table 5d. However, carrageenan remained 5 the primary gelling agent. Table 5d Active / Excipient Min % Max % Cetirizine Dihydrochloride 0.04 0.04 Water 98.75 98.82 Potassium sorbate 0.10 0.10 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.10 0.10 Kappa Carrageenan 0.32 0.32 Sodium alginate 0.10 0.17 Citric acid 0.12 0.12 Sodium citrate 0.34 0.34

[00108] They also determined it was desirable to add a sweetener and flavouring as illustrated in Table 5e. 10 Table 5e Active / Excipient Min % Max % Cetirizine Dihydrochloride 0.04 0.04 Water 98.57 98.67 Potassium sorbate 0.10 0.10 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.10 0.10 Kappa Carrageenan 0.32 0.32 Sodium alginate 0.14 0.14 Citric acid 0.12 0.12 Sodium citrate 0.34 0.34 Sucralose 0.02 0.02 Flavouring 0.10 0.20

[00109] Different flavourings tried demonstrated that different flavourings could be used.

[00110] Flavouring was finalised for the Cetirizine gel with three flavours: (i) blood orange, (ii) grape and (iii) menthol. The Cetirizine gel with menthol was too sweet with sorbitol so it was removed - See Table 1c. Sorbitol was kept with the blood orange and grape flavours - See Table 1d. Experimental series 3 (BCS class III)

[00111] Applicant explored a single gelling agent with a first exemplary class III API (Metformin).

[00112] Metformin was tested with two of their gel bases a) agar and gellan gum - Table 6a, and b) agar, kappa carrageenan and sodium alginate - Table 6b. Table 6a Active / Excipient Mass (g) Percentage (%) Metformin Hydrochloride 1.00 3.12 Water 25.00 77.89 Potassium sorbate 0.08 0.23 Agar 0.01 0.02 Gellan gum 0.15 0.47 Citric acid 0.05 0.14 Sodium citrate 0.25 0.78 Glycerol 5.57 17.35 Table 6b Active / Excipient Mass (g) Percentage (%) i) Metformin Hydrochloride 1.00 3.82 vii) Water 25.00 95.46 vi) Potassium sorbate 0.03 0.10 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.31 iii) Sodium alginate 0.02 0.08 v) Citric acid 0.02 0.08

[00113] The texture of metformin was ideal in using gel base in Table 6b as the appearance of the gel was clear, had no undissolved particulates, was bitter but not stinging in the mouth.

[00114] In comparison to the gel in Table 6a, the gel was translucent, had undissolved particulates, was bitter and salty. The texture was not ideal in appearance nor taste.

[00115] Accordingly, Applicant continued the development of metformin with the kappa carrageenan, alginate and agar base formulation - Table 6b.

[00116] Due to the bitterness of metformin, Applicant explored the use of emulsions.

[00117] Emulsions are created by combining an emulsifier, oil and water. The emulsifier and oil selected were lecithin and sunflower oil respectively.

[00118] The concentrations of sunflower oil were tested between 0.08% and 1.87% - See Table 6c. Table 6c Active / Excipient Min % Max % Metformin Hydrochloride 3.80 3.73 Water 57.01 55.99 Potassium sorbate 0.10 0.09 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.10 0.10 Kappa Carrageenan 0.30 0.30 Sodium alginate 0.08 0.08 Citric acid 0.08 0.08 Water (emulsion) 38.01 37.33 Lecithin 0.38 0.37 Sunflower Oil 0.08 1.87

[00119] Higher concentrations of oil were more helpful in reducing the bitterness. Different concentrations of lecithin were tested to determine the ideal ratio between emulsifier and oil - Table 6d. Table 6d Active / Excipient Min % Max % Metformin Hydrochloride 3.80 3.73 Water 57.01 55.89 Potassium sorbate 0.10 0.09 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.10 0.10 Kappa Carrageenan 0.30 0.30 Sodium alginate 0.08 0.08 Citric acid 0.08 0.08 Water (emulsion) 38.01 37.26 Lecithin 0.38 0.56 Sunflower Oil 0.08 1.86

[00120] The following formulation - Table 6e was most effective in reducing the bitter taste. 5 Table 6e Active / Excipient Mass (g) Percentage (%) Metformin Hydrochloride 1.00 3.79 Water 15.00 56.84 Potassium sorbate 0.03 0.09 Magnesium chloride 0.01 0.04 Potassium chloride 0.01 0.02 Agar 0.03 0.10 Kappa Carrageenan 0.08 0.30 Sodium alginate 0.02 0.08 Citric acid 0.02 0.08 Water (emulsion) 10.00 37.89 Lecithin 0.10 0.38 Sunflower Oil 0.10 0.38

[00121] As with Cetirizine dihydrochloride, Applicant was able to adjust sweetness (Table 6f) and flavouring (Table 6g). The sweetener used was sucralose and flavourings tested included the fruit flavours: strawberry, berry, watermelon, apple, cherry, grape, raspberry 10 and blood orange and menthol. Table 6f Active / Excipient Min % Max % Metformin Hydrochloride 3.79 3.79 Water 56.84 56.84 Potassium sorbate 0.09 0.09 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.10 0.10 Kappa Carrageenan 0.30 0.30 Sodium alginate 0.08 0.08 Citric acid 0.08 0.08 Water (emulsion) 37.89 37.89 Lecithin 0.38 0.38 Sunflower Oil 0.38 0.38 Sucralose 0.02 0.04 Table 6g Active / Excipient Min % Max % Metformin Hydrochloride 2.74 2.74 Water 68.43 68.60 Potassium sorbate 0.07 0.07 Magnesium chloride 0.03 0.03 Potassium chloride 0.01 0.01 Agar 0.07 0.07 Kappa Carrageenan 0.22 0.22 Sodium alginate 0.06 0.06 Citric acid 0.06 0.06 Water (emulsion) 27.37 27.44 Lecithin 0.27 0.27 Sunflower Oil 0.27 0.27 Sucralose 0.01 0.03 Flavouring 0.14 0.36

[00122] Sucralose was found to have quite an intense sweetness, and a more balanced 5 sweetness was obtained using a combination of sucralose with sorbitol - Table 6h. Table 6h Active / Excipient Min % Max % Metformin Hydrochloride 3.45 3.71 Water 51.82 55.67 Potassium sorbate 0.09 0.09 Magnesium chloride 0.04 0.04 Potassium chloride 0.02 0.02 Agar 0.09 0.10 Kappa Carrageenan 0.28 0.30 Sodium alginate 0.07 0.08 Citric acid 0.07 0.08 Water (emulsion) 34.55 37.11 Lecithin 0.35 0.37 Sunflower Oil 0.35 0.37 Sucralose 0.02 0.02 Flavouring 0.17 0.19 Sorbitol 1.86 8.64

[00123] Preferred formulations for metformin are illustrated in Tables 3c and 3d respectively.

Claims

1. A textured gel formulation capable of formulating Active Pharmaceutical Ingredients (APIs) spanning Biopharmaceutics Classification System (BCS) class I, II, and III comprising:i) a Biopharmaceutics Classification System (BCS) class I, II or III Active Pharmaceutical Ingredient (API), or a salt or solution thereof,ii) a primary gelling agent which is a carrageenan, iii) a first secondary gelling agent which is an alginate, iv) a second secondary gelling agent which is an agar, v) at least one cation donator,vi) a preservative,vii) at least one pH modifier, andviii) water.

2. A textured gel formulation as claimed in claim 1 which further comprises one or more of:ix) at least one sweetener,x) an emulsifier,xi) an oil, andxii) a flavouring.

3. A textured gel formulation as claimed in claim 1 wherein thev) at least one cation donator comprisesa. a divalent cation, and optionallyb. a monovalent cation.

4. A textured gel formulation as claimed in claim 3 whereina) the divalent cation is magnesium, andb) the monovalent cation is potassium.

5. A textured gel formulation as claimed in claim 3 or 4 wherein the v) cation donator is a chloride salt of the cation.

6. A textured gel formulation as claimed in claim 1 wherein thevi) preservative is potassium sorbate.

7. A textured gel formulation as claimed in claim 1 whereinvii) the at least one pH modifier is selected from citric acid, sodium citrate, and sodium bicarbonate.

8. A textured gel formulation as claimed in claim 7 wherein the pH is from PH4.0 to 7.5.

9. A textured gel formulation as claimed in claim 1 wherein iii) the alginate is present in a greater amount by weight than iv) the agar.with the proviso that the carrageenan is present in the greatest amount.

10. A textured gel formulation as claimed in claim 1 whereiniii) the alginate is present in a lesser amount by weight than iv) the agar.with the proviso that the carrageenan is present in the greatest amount.

11. A textured gel formulation as claimed in claim 1 wherein the gelling agents are present in a ratio, relative to the alginate, of from:ii) kappa carrageenan greater than 1.0 to 6.2,iv) agar 0.2 to 2.1, andiii) alginate 1.0.with the proviso that the carrageenan is present in the greatest amount.

12. A textured gel formulation as claimed in claim 11 wherein the gelling agents are present in a ratio, relative to the alginate, of from: ii) kappa carrageenan - 1.6 to 4.8,iv) agar-0.5 to 1.5, andiii) alginate -1.0.with the proviso that the carrageenan is present in the greatest amount.

13. A textured gel formulation as claimed in claim 11 wherein the kappa carrageenan, agar, and alginate are present in an amount, by weight % of the formulation, of ii) kappa carrageenan from 0.13 to 0.53, iv) agar from 0.02 to 0.18, and iii) alginate from 0.05 to 0.16.with the proviso that the carrageenan is present in the greatest amount.

14. A textured gel formulation as claimed in claim 13 wherein the kappa carrageenan, agar, and alginate are present in an amount, by weight % of the formulation, of ii) kappa carrageenan from 0.20 to 0.41, iv) agar from 0.06 to 0.13, and iii) alginate from 0.05 to 0.16.with the proviso that the carrageenan is present in the greatest amount.

15. A textured gel formulation as claimed in claim 2 whereinix) the sweetener is sucralose and I or sorbitol.

16. A textured gel formulation as claimed in claim 2 wherein x) the emulsifier is lecithin.

17. A textured gel formulation as claimed in claim 2 wherein xi) the oil is sunflower oil.

18. A textured gel formulation as claimed in claim 2 wherein xii) the flavouring is a fruit flavour or menthol.

19. A textured gel formulation as claimed in claim 1 wherein the API is a BCS class I compound.

20. A textured gel formulation as claimed in claim 1 wherein the API is a BCS class II compound.

21. A textured gel formulation as claimed in any of the preceding claim 1 wherein the API is a BCS class III compound.

22. A textured gel formulation as claimed in claim 19 wherein the API is Cetirizine chloride.

23. A textured gel formulation as claimed in claim 22 wherein the formulation comprises ingredients (by weight %) in the range as Table 1a.Table 1aActive / Excipient Min % Max% viii) Water 65.00 to 100.00 vii) pH modifier(s) 0.08 0.50 i) Cetirizine Dihydrochloride 0.02 0.06 vi) Preservative 0.04 0.20v) Divalent Cation 0.02 0.06 v) Monovalent Cation 0.01 0.03 iv) Agar 0.06 0.20 ii) Carrageenan 0.20 0.50 iii) Sodium Alginate 0.09 0.20 xii) Flavouring 0.06 0.20 ix) Sweetener(s) 0.00 10.0024. A textured gel formulation as claimed in claim 23 wherein the formulation comprises ingredients (by weight %) in the range as Table 1bTable 1b Active / Excipient Min % Max% viii) Water 64.01 to 100.00 vii) Citric Acid 0.08 0.14 vii) Sodium Citrate 0.22 0.41 i) Cetirizine Dihydrochloride 0.03 0.05 vi) Potassium Sorbate 0.06 0.12 v) Magnesium Chloride 0.03 0.05 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.07 0.12 ii) Kappa Carrageenan 0.20 0.38 iii) Sodium Alginate 0.09 0.16 xii) Flavouring 0.06 0.12 ix) Sucralose 0.01 0.02 ix) Sorbitol 0.00 9.515 25. A textured gel formulation as claimed in claim 24 wherein the formulationcomprises ingredients (by weight (g) or weight %) as set out in Table 1c or 1dTable 1cActive / Excipient Mass (g) Percentage (%) viii) Water 25.00 98.67 vii) Citric Acid 0.03 0.12 vii) Sodium Citrate 0.09 0.34 i) Cetirizine Dihydrochloride 0.01 0.04 vi) Potassium Sorbate 0.03 0.10 v) Magnesium Chloride 0.01 0.04 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.32 iii) Sodium Alginate 0.03 0.14 xii) Flavouring - Menthol 0.03 0.10 ix) Sucralose 0.01 0.02 Total 25.34 100.00Active / Excipient Mass (g) Percentage (%) viii) Water 25.00 91.45 vii) Citric Acid 0.03 0.11 vii) Sodium Citrate 0.09 0.32 i) Cetirizine Dihydrochloride 0.01 0.04 vi) Potassium Sorbate 0.03 0.09 v) Magnesium Chloride 0.01 0.04 v) Potassium Chloride 0.01 0.02 iv) Agar Agar 0.03 0.09 ii) Kappa Carrageenan 0.08 0.29 iii) Sodium Alginate 0.03 0.13 xii) Flavouring - Blood Orange or Grape 0.03 0.09 ix) Sucralose 0.01 0.02 ix) Sorbitol 2.00 7.32 Total 27.34 100.0026. A textured gel formulation as claimed in claim 20 wherein the API is sodium ibuprofen.5 27. A textured gel formulation as claimed in claim 26 wherein the formulationcomprises ingredients (by weight %) in the range as Table 2a.Table 2aActive / Excipient Min % Max% viii) Water 65.00 to 100.00 i) Ibuprofen Sodium 0.60 1.40 vi) Preservative 0.01 0.20 v) Divalent Cation 0.02 0.07 v) Monovalent Cation 0.01 0.04 vii) pH modifier(s) 0.05 0.70 iv) Agar 0.05 0.20 ii) Carrageenan 0.10 0.45 iii) Alginate 0.04 0.2028. A textured gel formulation as claimed in claim 27 wherein the formulation comprises ingredients (by weight %) in the range as Table 2bTable 2bActive / Excipient Min % Max% viii) Water 68.44 to 100.00 i) Ibuprofen Sodium 0.70 1.30 vi) Potassium sorbate 0.07 0.13 v) Magnesium chloride 0.03 0.06 v) Potassium chloride 0.01 0.03 vii) Sodium bicarbonate 0.34 0.64 vii) Citric acid 0.06 0.11iv) Agar 0.07 0.13 ii) Kappa Carrageenan 0.22 0.41 iii) Sodium alginate 0.06 0.1129. A textured gel formulation as claimed in claim 28 wherein the formulation comprises ingredients (by weight (g) or weight %) as set out Table 2cTable 2cActive / Excipient Mass (g) Percentage (%) viii) Water 25.00 97.77 i) Ibuprofen Sodium 0.26 1.00 vi) Potassium sorbate 0.03 0.10 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Sodium bicarbonate 0.13 0.49 vii) Citric acid 0.02 0.08 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.31 iii) Sodium alginate 0.02 0.08 Total 25.57 100.005 30. A textured gel formulation as claimed in claim 21 wherein the API is Metforminhydrochloride31. A textured gel formulation as claimed in claim 30 wherein the formulation comprises ingredients (by weight %) in the range as Table 3a.Table 3aActive / Excipient Min % Max% viii) Water 55.00 to 100.00 vi) Preservative 0.05 0.15 v) Divalent cation 0.02 0.06 v) Monovalent cation 0.01 0.03 vii) pH modifier 0.04 0.40 iv) Agar 0.04 0.40 ii) Carrageenan 0.15 1.20 iii) Alginate 0.04 0.35 ix) Sweetener 0.00 10.00 xi) Oil 0.05 4.00 x) Emulsifier 0.20 0.60 i) Metformin hydrochloride 0.03 4.00 xii) Flavouring 0.10 0.8532. A textured gel formulation as claimed in claim 31 wherein the formulation comprises ingredients (by weight %) in the range as Table 3bActive / Excipient Min % Max% viii) Water 62.63 to 100.00 vi) Potassium sorbate 0.06 0.12 v) Magnesium chloride 0.03 0.05 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.05 0.10 iv) Agar 0.06 0.12 ii) Kappa Carrageenan 0.20 0.37 iii) Sodium alginate 0.05 0.10 ix) Sweetener 0.00 9.30 xi) Sunflower Oil 0.25 0.47 x) Lecithin 0.25 0.47 i) Metformin hydrochloride 1.25 2.33 xii) Flavouring 0.13 0.23 ix) Sucralose 0.01 0.0233. A textured gel formulation as claimed in claim 32 wherein the formulation comprises ingredients (by weight (g) or weight %) as set out Table 3c and 3dTable 3cActive / Excipient Mass (g) Percentage (%) viii) Water 25.00 94.54 vi) Potassium sorbate 0.03 0.09 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.02 0.08 iv) Agar 0.03 0.10 ii) Kappa Carrageenan 0.08 0.30 iii) Sodium alginate 0.02 0.08 xi) Sunflower Oil 0.10 0.38 x) Lecithin 0.10 0.38 i) Metformin hydrochloride 1.00 3.78 xii) Flavouring - Menthol 0.05 0.19 ix) Sucralose 0.01 0.02 Total 26.44 100.00Table 3dActive / Excipient Mass (g) Percentage (%) viii) Water 25.00 87.89 vi) Potassium sorbate 0.03 0.09 v) Magnesium chloride 0.01 0.04 v) Potassium chloride 0.01 0.02 vii) Citric acid 0.02 0.07 iv) Agar 0.03 0.09 ii) Kappa Carrageenan 0.08 0.28 iii) Sodium alginate 0.02 0.08 ix) Sorbitol 2.00 7.03 xi) Sunflower Oil 0.10 0.35x) Lecithin 0.10 0.35 i) Metformin hydrochloride 1.00 3.52 xii) Flavouring - Blood Orange or Grape 0.05 0.18 ix) Sucralose 0.01 0.02 Total 28.44 100.00s

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