Liquid oral formulation of famotidine or pharmaceutically acceptable salt thereof

Abstract

The present invention relates to oral liquid formulation of famotidine or pharmaceutically acceptable salt thereof. The present invention also relates to the process for the preparation of said liquid formulation. The liquid formulation is in the form of solution, suspension, powder for suspension or powder for solution.

Description

[0001] Liquid oral formulation of famotidine or pharmaceutically acceptable salt thereof

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to oral liquid formulation of famotidine or pharmaceutically acceptable salt thereof. The present invention also relates to the process for the preparation of said liquid formulation.

[0004] BACKGROUND OF THE INVENTION

[0005] Gastrointestinal diseases are most likely to happen due to several reasons. These conditions include constipation, irritable bowel syndrome (IBS), nausea, food poisoning, gas, bloating, gastroesophagal reflux disease (GERD), gastric or duodenal ulcers etc.

[0006] The most effective treatment approach for gastric or duodenal ulcer, common heartburn and GERD is selective histamine type 2 receptor antagonists / blockers (H2 blockers). The H2 receptor blockers bind to basolateral surface of gastric parietal cells. This interferes with the gastric acid production and secretion. There are several potent H2 receptor antagonists like cimetidine, ranitidine, famotidine, nizatidine. Famotidine has advantages over cimetidine and ranitidine.

[0007] Famotidine is chemically known as N'-(aminosulfonyl)-3-2-(diaminomethylene)amino-4- thiazolylmethylthiopropanimidamide and it is first disclosed in GB2055800B. EP0297019B1 discloses the polymorphic forms of Famotidine and their synthesis procedures.

[0008] W02000025754 discloses the solid oral dosage form containing Famotidine and alginic acid, wherein Famotidine is separated from alginic acid by impermeable barrier in a solid dosage form.

[0009] Generally, paediatric and geriatric patients face the problem for swallowing solid dosage form. There is a conventional practice to formulate extemporaneous Liquid oral formulation for patients having difficulties in swallowing the solid dosage form. The extemporaneous Liquid oral formulation involves triturating Famotidine tablets and dispensed it in distilled water. This compromises the accurate dosing of the drug and dose adjustment. The shelf life of such customized formulation is very short, up to about 20 days. There are several other instances where the H2 -blocker is combined with antacid in an oral formulation. But, this may lead to worsen the adverse effects by prolong use of antacids. Antacids like calcium carbonate induce hypercalcemia and conditions like milk-alkali syndrome while aluminium hydroxide can also induce serious conditions like neurotoxicity along with constipation, vomiting, osteomalachia etc. Sodium bicarbonate when used as antacid tends to increase the excretion of acidic drugs like aspirin while the renal elimination of basic drugs is altered.

[0010] Famotidine is marketed commercially in the United States as Pepcid®, as immediate release oral tablet, rapidly disintegrating tablet, powder for reconstitution as an oral suspension, and injectable solution. Pepcid® label states that each 5 mL of PEPCID for oral suspension when prepared as directed contains 40 mg of famotidine and the following inactive ingredients: citric acid, flavors (cherry, banana, and mint), microcrystalline cellulose and carbo xymethylcellulose sodium sucrose and xanthan gum, and sodium benzoate 0.1%, sodium methylparaben 0.1% and sodium propylparaben 0.02% as preservatives.

[0011] Therefore, the objective behind the present invention is to formulate a stable oral liquid formulation of Famotidine and to achieve better shelf life and bioavailability.

[0012] SUMMARY OF THE INVENTION

[0013] The present invention relates to oral liquid formulation of famotidine or pharmaceutically acceptable salt thereof. The present invention also relates to the process for the preparation of said liquid formulation. The liquid formulation is in the form of ready to use solution, ready to use suspension, powder for suspension or powder for solution.

[0014] In one embodiment of the present invention, there is provided a stable oral liquid formulation comprising famotidine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable ingredient, wherein the formulation is stable for at least one month under storage condition of 25°C / 60% RH and / or 2-8°C.

[0015] In another embodiment of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; and c) one or more pharmaceutically acceptable ingredients.

[0016] In yet another embodiment of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; and c) one or more pharmaceutically acceptable ingredients, wherein the liquid formulation is free of xanthan gum.

[0017] In another embodiment of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; and c) one or more pharmaceutically acceptable ingredients, wherein the liquid formulation is free of surfactant.

[0018] In a further embodiment of the present invention, there is provided a process for preparation of a stable liquid formulation comprising famotidine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein process utilized is blending, dry granulation, wet granulation, spheronization extrusion process, hot melt extrusion process, homogenization or the like.

[0019] In another embodiment of the present invention, there is provided a process for the preparation of stable liquid formulation comprising famotidine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the process comprises following steps:

[0020] (i) dissolving / dispersing one or more pharmaceutically acceptable excipients in a portion of water;

[0021] (ii) dispersing famotidine or pharmaceutically acceptable salt thereof in the in a portion of water;

[0022] (iii) adding the mixture of step (ii) to the mixture of step (i);

[0023] (iv) mixing suspending agent in another portion of water;

[0024] (v) adding the mixture of step (iv) to the mixture of step (iii); and (vi) optionally, adding one or more pharmaceutically acceptable excipients to the dispersion of step (v); and

[0025] (vii) optionally, homogenizing the mixture of step (vi) to form a suspension.

[0026] DETAILED DESCRIPTION OF THE INVENTION

[0027] As used herein, the term "ready to use suspension" means a pre-constituted suspension which can be administered as such. The "powder for suspension" or "dry suspension" needs to be reconstituted with a liquid carrier to form a suspension.

[0028] As used herein, the term "famotidine" is used in broad sense to include not only famotidine per se but also its pharmaceutically acceptable salts, solvates, hydrates, enantiomers, derivatives, isomers, polymorphs, prodrugs thereof, and also its various crystalline and amorphous forms.

[0029] The term "stable," as used herein, refers to chemical stability, wherein not more than 2.5% w / w of total related substances are formed at 25°C / 60% relative humidity (R.H.) or on storage at 2-8°C for a period of at least one month, particularly for a period of two months, more particularly for a period of at least three months, and preferably for six months.

[0030] The present invention relates to oral liquid formulation of famotidine or pharmaceutically acceptable salt thereof. The present invention also relates to the process for the preparation of said liquid formulation. The liquid formulation is in the form of solution, suspension, powder for suspension or powder for solution.

[0031] In one embodiment of the present invention, there is provided a stable oral liquid formulation comprising famotidine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable ingredient, wherein the formulation is stable for at least one month under storage condition of 25°C / 60% RH and / or 2-8°C.

[0032] In one aspect of the present invention, the formulation is stable for at least two months under storage condition of 25°C / 60% RH and / or 2- 8 °C. In another aspect of the present invention, the formulation is stable for at least three months under storage condition of 25°C / 60% RH and / or 2- 8 °C. In yet another aspect of the present invention, the formulation is stable for at least six months under storage condition of 25°C / 60% RH and / or 2-8°C. In another embodiment of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; and c) one or more pharmaceutically acceptable ingredients.

[0033] In yet another embodiment of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; and c) one or more pharmaceutically acceptable ingredients, wherein the liquid formulation is free of xanthan gum.

[0034] In another embodiment of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; and c) one or more pharmaceutically acceptable ingredients, wherein the liquid formulation is free of surfactant.

[0035] In one aspect of the present invention, the oral liquid formulation of famotidine exhibits an in-vitro dissolution rate of more than 75% of drug release within 30 minutes, when said dosage form is placed in a dissolution vessel filled with 1000 ml of acetate buffer, pH 4.5 maintained at 37+0.5°C and stirred at a paddle speed of 100 rpm using a USP Type II (paddle) apparatus.

[0036] In one aspect of the present invention, the oral liquid formulation of famotidine is in the form of a ready to use oral solution. In another aspect of the present invention, the oral liquid formulation of famotidine is in the form of a ready to use oral suspension. In yet another aspect of the present invention, the oral liquid formulation of famotidine is in the form of a powder for reconstitution. In further aspect of the present invention, the oral liquid formulation of famotidine is in the form of a powder for reconstitution, wherein said powder contains either granular mixture or dry powder. In one embodiment of the invention, famotidine is present at a concentration of lOmg / mL, 20mg / mL, 30mg / mL, 40mg / mL, 50mg / mL, 60mg / mL, 70mg / mL or 80mg / mL. In one aspect of the invention, famotidine is present at a concentration of 40mg / mL or 80mg / mL.

[0037] In one aspect of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; c) a preservative and d) optionally, one or more pharmaceutically acceptable ingredients.

[0038] In another aspect of the present invention, there is provided a stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; c) a preservative and d) pH adjusting agent in sufficient amounts to maintain the pH of the formulation in the range of about 3.0 to about 8.0; and e) optionally, pharmaceutically acceptable vehicle.

[0039] In one aspect of the present invention, the pH of the formulation is in the range of about 3.0 to about 8.0. In another aspect of the present invention, the pH of the formulation is in the range of about 4.0 to about 8.0. In yet another aspect of the present invention, the pH of the formulation is in the range of about 6.0 to about 8.0. In further aspect of the present invention, the pH of the formulation is in the range of about 6.0 to about 7.5, preferably, about 6.0 to about 7.0.

[0040] In one aspect on the invention, famotidine has a particle size distribution D90 less than about 200 pm or less about 150 pm, less about 100 pm, less about 50 pm or less about 20 pm.

[0041] In one embodiment of the present invention, there is provided a process for preparation of a stable liquid formulation comprising famotidine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein process utilized is blending, dry granulation, wet granulation, spheronization extrusion process, hot melt extrusion process, homogenization or the like.

[0042] In another embodiment of the present invention, there is provided a process for the preparation of stable liquid formulation comprising famotidine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, wherein the process comprises following steps:

[0043] (i) dissolving / dispersing one or more pharmaceutically acceptable excipients in a portion of water;

[0044] (ii) dispersing famotidine or pharmaceutically acceptable salt thereof in the in a portion of water;

[0045] (iii) adding the mixture of step (ii) to the mixture of step (i);

[0046] (iv) mixing suspending agent in another portion of water;

[0047] (v) adding the mixture of step (iv) to the mixture of step (iii); and

[0048] (vi) optionally, adding one or more pharmaceutically acceptable excipients to the dispersion of step (v); and

[0049] (vii) optionally, homogenizing the mixture of step (vi) to form a suspension.

[0050] The one or more pharmaceutically acceptable ingredients are selected from group consisting of suspending agents / viscosity agents / thickening agents, buffers / pH adjusting agents, preservatives, anticaking agents, diluents, antioxidants, solubilizers, surfactants / wetting agents, complexing agents, antifoaming agents, sweeteners, flavouring agents, lubricants and suitable vehicle.

[0051] Suspending agents / viscosity agents / thickening agents are selected from group consisting of cellulose derivatives such as hydroxy ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methylcellulose, carbo xymethyl cellulose and its salts / derivatives such as carbo xymethyl cellulose sodium, microcrystalline cellulose, and coprocessed spray dried forms of microcrystalline cellulose and carboxymethyl cellulose sodium (available as Avicel RC-501, Avicel RC-581, Avicel RC-591 and Avicel CL-611); carbo mers; gums such as xanthan gum, locust bean gum, tragacanth gum, arabinogalactan gum, agar gum, gellan gum, guar gum, apricot gum, karaya gum, sterculia gum, acacia gum, gum arabic, and carrageenan; pectin; propylene glycol alginate, dextran; gelatin; polyethylene glycols; polyvinyl compounds such as polyvinyl acetate, polyvinyl alcohol, and polyvinyl pyrrolidone; sugar alcohols such as xylitol and mannitol; colloidal silica; maltodextrin, starch; and mixtures thereof. The suspending agents / viscosity agents are present in an amount of about 0.05% to about 10% w / v of the formulation. Particularly, the viscosity agents are present in an amount of about 0.1% to about 10% w / v of the formulation. More particularly, the viscosity agents are present in an amount of about 0.1% to about 5% w / v of the formulation. Preferably, the viscosity agents are present in an amount of about 0.1% to about 3% w / v of the formulation.

[0052] Preservatives, which may be used according to the present invention, include, but are not limited to, benzoic acid, sodium benzoate, potassium sorbate, cresol, cetrimide, citric acid and sodium citrate, and alkyl hydroxybenzoates (parabens). Preferably, the preservative is selected from an alkyl hydroxybenzoate, such as methyl hydroxybenzoate (MHB), ethyl hydroxybenzoate (EHB), propyl hydroxybenzoate (PHB) (as base or sodium salt) or a combination thereof. Preferably, the preservative is combination of MHB and PHB. More preferably, the preservative is combination of Na MHB and Na PHB. Preservative can be present in an amount from about 0.001 to about 1% w / v of the liquid formulation, preferably about 0.01 to about 0.5% w / v of the liquid formulation.

[0053] Various useful diluents include, but are not limited to mannitol, sucrose, sugar alcohols, sorbitol, xylitol, erythritol, starch, pregelatinized starch, calcium carbonate, calcium phosphate, dibasic anhydrous, calcium phosphate, dibasic dihydrate, calcium phosphate tribasic, calcium sulphate, cellulose powdered, silicified microcrystalline cellulose, cellulose acetate, lactose, magnesium carbonate, magnesium oxide, maltodextrin, microcrystalline cellulose, polydextrose, sodium alginate, sodium chloride and or mixtures thereof. Preferably diluent used is mannitol. The diluent is present in an amount of 0.1 to 20 % w / v of the liquid formulation.

[0054] Various useful pH adjusting agent or buffering agents include, but are not limited to, citrate buffers, phosphate buffers, or monosodium dibasic phosphate, gluconic acid, lactic acid, citric acid, acetic acid, sodium gluconate, sodium lactate, sodium citrate, sodium acetate, potassium citrate, sodium bicarbonate, potassium bicarbonate, sodium dihydrogen phosphate and potassium dihydrogen phosphate. Suitable surfactant or wetting agents are selected from the group consisting of non-ionic, anionic, cationic, or zwitterionic surfactants, and combinations thereof. Suitable examples of wetting agents are sodium lauryl sulphate; cetrimide; polyethylene glycols; polyglycerin fatty acid esters such as decaglyceryl monolaurate and decaglyceryl mo no myristate; sorbitan fatty acid esters such as sorbitan monostearate; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monooleate; polyoxyethylene alkyl ether such as polyoxyethylene lauryl ether; polyoxyethylene castor oil; polyoxyethylene-polyoxypropylene block copolymers such as poloxamers (e.g. Poloxamer 188); and combinations thereof. The surfactant or wetting agents are present in an amount of about 0.01% to about 1% w / v of the formulation.

[0055] Various useful Anticaking agents include, but are not limited to, colloidal silica, colloidal silicon dioxide, calcium phosphate tribasic, magnesium oxide, magnesium silicate, calcium silicate and combinations thereof. The anticaking agents are present in an amount of about 0.1% to about 10% w / v of the formulation.

[0056] Various useful antioxidants include, but are not limited to, EDTA, Disodium EDTA, ascorbic acid, tert-butylhydroquinone, sodium pyrosulfite, glutathione, sodium bisulfite, sodium sulfite, a-tocopherol, a-tocopherol acetate, monothioglycerol, cysteine, ascorbyl palmitate, acetylcysteine, dithiothreitol, sodium metabisulfite, thiourea, sodium thiosulfate, butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate.

[0057] Anti-foaming agent can be a silicone based antifoam. Antifoaming agent is preferably simethicone emulsion. The antifoaming agent can be present in an amount from about 0.01 to about 1% w / v of the liquid formulation.

[0058] Complexing agents, which may be used according to the present invention, include, but are not limited to, a-cyclodextrin, P-cyclodextrin, y-cyclodextrin and their derivatives such as, for example, hydroxypropyl- P-cyclodextrin.

[0059] Sweeteners, which may be used according to the present invention, may be any natural or artificial sweetener. In terms of natural sweeteners, these include, but are not limited to, glucose, fructose, invert sugar, sorbitol, sucrose, maltose, xylose, ribose, mannose, corn syrup solids, xylitol, mannitol, maltodextrins, and mixtures thereof. In terms of artificial sweeteners, these include, but are not limited to, sucralose, aspartame and saccharin. In one embodiment, the artificial sweetener is sucralose. Sweetener can be present in an amount from about 0.01% to about 20% w / v of the liquid formulation.

[0060] Flavouring agents incorporated in the liquid formulation may be chosen from synthetic flavor oils and flavoring aromatics and / or natural oils, extracts from plant leaves, flowers, fruits, and so forth and combinations thereof. Also useful as flavors are mix fruit flavour, natural mint flavour, vanilla, citrus oils, including lemon, orange, lime and grapefruit, and fruit essence, including apple, grape, banana, pear, peach, strawberry, raspberry, cherry, plum, pineapple, apricot, and so forth. Flavouring agent can be present in an amount from about 0.01% to about 1% w / v of the liquid formulation.

[0061] Vehicle / liquid carrier used in the formulation of the present invention include aqueous and non-aqueous carrier but are not limited to water, alcohol, polyethylene glycol, propylene glycol, oil, or combinations thereof. Particularly, the suspensions are aqueous based. By "aqueous carrier" is meant a suspension comprising water, or a combination of water and a water-miscible organic solvent or solvents. Water-miscible solvents include but are not limited to propylene glycol, polyethylene glycol and ethanol. By "non-aqueous carrier" is meant a suspension in which the carrier does not include water. The carrier can also include one more pharmaceutically acceptable excipients which can be in dissolved or dispersed form. The liquid carrier is present in an amount from about 30% w / v to about 95% w / v, particularly from about 50% w / v to about 95% w / v.

[0062] While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. The invention is further illustrated by the following non-limiting examples which are provided for illustrative purposes only in order to facilitate a more complete understanding of representative embodiments. These examples should not be construed to limit any of the embodiments described in the present specification. EXAMPLES

[0063] Example 1 - Famotidine 40mg / 5ml Oral Suspension

[0064] Manufacturing Process:

[0065] 1. Sodium MHB and Sodium PHB were dissolved in part quantity of water and mixed to get clear solution.

[0066] 2. Sucralose was added in above solution and mixed to get clear solution.

[0067] 3. Famotidine and Disodium EDTA were mixed with small amount of water and added to above solution and mixed to get uniformly dispersed suspension.

[0068] 4. Sodium CMC was slowly added into above solution and mixed to get uniformly dispersed suspension.

[0069] 5. Anhydrous citric acid was added into above dispersion and mix for 5 minutes. The pH of suspension was 6.0 to 6.5.

[0070] 6. Mix fruit flavour was added to above suspension and stirred for 10 minutes.

[0071] 7. Colloidal Silicon Dioxide was added and mixed.

[0072] 8. The volume was adjusted with purified water. Example 2 - Stability study

[0073] Stability data of suspension formulation of example 1, packed in glass bottle is shown below.

[0074] Suspension formulation of example 1 found to be stable wherein assay is within 95.0% to 105.0% w / w, any individual impurity less than 0.50% w / w, any unknown impurity less than

[0075] 0.20% w / w and total impurity is less than 2.5% w / w.

[0076] Example 3 - Famotidine Powder for Oral Suspension Avicel RC 591 is a mixture of microcrystalline cellulose and carbo xymethylcellulose sodium manufactured by DuPont.

[0077] Aerosil 200 is hydrophilic fumed silica manufactured by Evonik. Manufacturing Process:

[0078] 1. Aerosil-200 and Avicel RC 591 were co-sifted through 40 # sieve.

[0079] 2. Famotidine and Mannitol were co-sifted through 40# sieve.

[0080] 3. Step 1 and step 2 were co-sifted through 40# sieve.

[0081] 4. Sift the Sodium MHB, Sodium PHB, Sucralose and Natural Mint Flavor were sifted from 40 # sieve.

[0082] 5. Step 3 and Step 4 Blend co-sifted from 40# sieve.

[0083] 6. Step 5 was blended in Octagonal Blender for 15 minutes at 12 RPM.

[0084] 7. Required weight of granules was filled in Amber color glass bottle.

[0085] Example 4 - Stability study

[0086] Stability data of suspension formulation of example 3, packed in Amber color glass bottle is shown below.

[0087] Suspension formulation of example 3 found to be stable wherein assay is within 95.0% to 105.0% w / w, any individual impurity less than 0.50% w / w, any unknown impurity less than 0.20% w / w and total impurity is less than 2.5% w / w.

Claims

Claims:

1. A stable oral liquid formulation comprising famotidine or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable ingredient, wherein the formulation is stable for at least one month under storage condition of 25°C / 60% RH and / or 2-8°C.

2. A stable oral liquid formulation comprising: a) famotidine or pharmaceutically acceptable salt thereof from about 0.1-10% w / v; b) a suspending agent from about 0.05-10% w / v; and c) one or more pharmaceutically acceptable ingredients.

3. The stable liquid formulation as claimed in claim 1 or 2, wherein liquid formulation is in the form of ready to use solution, ready to use suspension, powder for suspension or powder for solution.

4. The stable oral liquid formulation as claimed in claim 1 or 2, wherein the pH of the formulation is in the range of about 3.0 to about 8.0.

5. The stable oral liquid formulation as claimed in claim 1 or 2, wherein famotidine has a particle size distribution D90 less than about 200 pm.

6. The stable oral liquid formulation as claimed in claim 1 or 2, wherein the one or more pharmaceutically acceptable ingredients are selected from group consisting of suspending / viscosity agents, buffers (pH adjusting agents), preservatives, anticaking agents, antioxidants, solubilizers, surfactants or wetting agents, complexing agents, antifoaming agents, sweeteners, flavouring agents, lubricants and suitable vehicle.

7. The stable oral liquid formulation as claimed in claim 6, wherein the pH adjusting agent is citrate buffers, phosphate buffers, or monosodium dibasic phosphate, gluconic acid, lactic acid, citric acid, acetic acid, sodium gluconate, sodium lactate, sodium citrate, sodium acetate potassium citrate, sodium bicarbonate, potassium bicarbonate, sodium dihydrogen phosphate and potassium dihydrogen phosphate.

8. The stable oral liquid formulation as claimed in claim 7, wherein the pH adjusting agent is citric acid.

9. The stable oral liquid formulation as claimed in claim 6, wherein the suspending agent is selected from group consisting of cellulose derivatives such as hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methylcellulose, carbo xymethyl cellulose and its salts / derivatives such as carbo xymethyl cellulose sodium, microcrystalline cellulose, and co-processed spray dried forms of microcrystalline cellulose and carbo xymethyl cellulose sodium.

10. The stable oral liquid formulation as claimed in claim 6, wherein the preservative is selected from benzoic acid, sodium benzoate, potassium sorbate, cresol, cetrimide, citric acid and sodium citrate, and alkyl hydroxybenzoates (parabens).

11. The stable oral liquid formulation as claimed in claim 6, wherein the preservative is present in an amount from about 0.001 to about 1% w / v of the liquid formulation.

12. The stable oral liquid formulation as claimed in claim 6, wherein the sweetener is present in an amount from about 0.01% to about 20% w / v of the liquid formulation.

13. The stable oral liquid formulation as claimed in claim 6, wherein the vehicle is water, alcohol, polyethylene glycol, propylene glycol, oil, or combinations thereof.

14. The stable oral liquid formulation as claimed in claim 13, wherein the vehicle is water.

15. The stable oral liquid formulation as claimed in claim 14, wherein the water is present in an amount from about 30% w / v to about 95% w / v.

16. The stable oral liquid formulation as claimed in claim 1 or 2, wherein the liquid formulation is free of xanthan gum.

17. The stable oral liquid formulation as claimed in claim 1 or 2, wherein the liquid formulation is free of surfactant.

18. A process for the preparation of stable liquid formulation of claim 6, wherein the liquid formulation is prepared by the process comprising following steps:(i) dissolving / dispersing one or more pharmaceutically acceptable excipients in a portion of water;(ii) dispersing famotidine or pharmaceutically acceptable salt thereof in the in a portion of water;(iii) adding the mixture of step (ii) to the mixture of step (i);(iv) mixing suspending agent in another portion of water;(v) adding the mixture of step (iv) to the mixture of step (iii); and(vi) optionally, adding one or more pharmaceutically acceptable excipients to the dispersion of step (v); and(vii) optionally, homogenizing the mixture of step (vi) to form a suspension.

19. A process for the preparation of stable liquid formulation of claim 6, wherein the process utilized is blending, dry granulation, wet granulation, spheronization extrusion process, hot melt extrusion process, homogenization.

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