FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2010
COMPLETE SPECIFICATION
(See section 10; rule 13)
"STABLE LIQUID PHARMACEUTICAL COMPOSITIONS OF RANITIDINE"
CADILA PHARMACEUTICALS LIMITED
"Cadila Corporate Campus", Sarkhej - Dholka Road, Bhat, Ahmedabad - 382210, Gujarat,
India
The following specification particularly describes the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention relates to stable oral liquid pharmaceutical compositions of ranitidine or its pharmaceutically acceptable salts.
BACKGROUND OF THE INVENTION
Ranitidine HCI is a potent histamine H2 -antagonist and widely used in the treatment of gastric acidity. Such conditions include duodenal and gastric ulceration, reflux oesophagitis and Zollinger-Ellison syndrome.
Ranitidine HCI is subject to degradation in the presence of humidity, temperature, light and oxygen. Numerous effort have been made in past to prevent the degradation of ranitidine and to improve the stability of the ranitidine in pharmaceutical composition particularly in liquid pharmaceutical composition. Followings are the prior art that disclose the use of different excipients to improve the stability of ranitidine in liquid pharmaceutical composition.
US4128658 discloses liquid formulations of Ranitidine and its pharmaceutically acceptable salts for oral and parenteral administrations wherein hydrochloric acid has been used to achieve the pH value of 5.0 in the formulation. Though such formulations are therapeutically effective but they are having a relatively short shelf life due to the degradation of the ranitidine.
US4585790 describes aqueous formulations of ranitidine with enhanced shelf life. The pH of the formulation is adjusted in the range of 6,5 - 7.5 with use of suitable buffer salts like potassium dihydrogen orthophosphate, disoium hydrogen orthophosphate and citric acid. However US458790 does not produce any stability data in specification to prove the stability of said aqueous formulation.
US5068249 discloses stable, aqueous formulations of ranitidine containing ethanol as a stabilizer in the range of 2.5 to 10% w/v. It is undesirable to use alcohol in oral formulations especially used for pediatric patients.
US6265449 discloses an aqueous pharmaceutical composition for oral administration comprising ranitidine, or a pharmaceutically acceptable salt thereof, that contains alcohol and low color, metal, turbidity (LCMT) sucrose, which was found to improve the stability,

bioavailability and taste-masking of ranitidine. However, the use of (LCMT) sucrose in pharmaceutical composition is not economical.
US2006100271 describes an ethanol-free aqueous pharmaceutical ranitidine composition, or pharmaceutically acceptable salts thereof, which is stabilized with hydroxyethyl cellulose. The said composition also includes methyl paraben, and either sorbitol or sucrose. The compositions disclosed in US2006100271 show the color change, which is evidencing the degradation of ranitidine in the aqueous pharmaceutical compositions.
The above prior art describes liquid pharmaceutical compositions of ranitidine wherein combinations of different stabilizing excipients with buffer or ethanol have been used to improve the stability of ranitidine in liquid pharmaceutical composition. As stated above that it is desired to avoid the use of alcohol in liquid pharmaceutical composition. Presence of Buffers in oral liquid composition may degrade the ranitidine and make the formulation unstable by reacting with the drug.
Hence there is an unmet need to develop the stable oral liquid pharmaceutical composition with a prolonged shelf life, which also improves the patient compliance.
OBJECTIVE OF THE INVENTION
The main object of the invention is to provide the stable, palatable, oral liquid compositions of ranitidine or its pharmaceutically acceptable salts.
Another object of the invention is to provide the stable oral liquid compositions of ranitidine or its pharmaceutically acceptable salts without using alcohol, buffer, non-ionic water-soluble polymer derived from cellulose (Hydroxyethyl cellulose), LCMT sucrose and polyethylene glycol or combination there of.
Another object of the invention is to provide the palatable oral liquid compositions of ranitidine or it's pharmaceutically acceptable salts having stability of 18 months or more when stored at room temperature condition (25°C) and without refrigeration.

Another object of the invention is to provide the stable, palatable oral liquid compositions of ranitidine or its pharmaceutically acceptable salts with water content is not more than 50% at pH value of les than 7.5.
SUMMARY OF THE INVENTION
It has been surprisingly found that aqueous liquid compositions comprising ranitidine or its physiologically acceptable salts can be stabilized without the use of ethanol and/or buffers as taught in US patents 5068249, 4585790 and 6265449. In particular, it has been found that ranitidine is stable in the presence of co-solvent and stability is achieved by using co-solvent at 15 to 50% w/v concentration range for 18 months or more when stored at room temperature condition.
The co-solvent according to present invention is glycerin, maltitol, sorbitol and propylene glycol which is used in the range of 15 to 50% concentration and helps to improve the stability of the formulation and useful for masking the taste of the ranitidine.
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the invention relates to stable palatable liquid oral pharmaceutical compositions consist essentially of ranitidine hydrochloride, co-solvent, antioxidant, water, pH modifier/adjusting agent and resin.
Stable liquid oral pharmaceutical compositions optionally contain stabilizers, viscosity modifiers, preservatives, sweeteners, anti-caking agents, pharmaceutical-grade dyes/pigments, and flavoring agents.
Co-solvents are selected from glycerin, maltitol, sorbitol and propylene glycol, in the range of 15 to 50% w/w, preferably 20 to 40% w/w, most preferably 25 to 35%. The preferred co-solvent is glycerin.
Antioxidants are selected from butyiated hydroxy anisole, butylated hydroxy toluene, sodium metabisulfite, propyl gallate, L-cysteine hydrochloride, vitamin E acetate, ascorbic acids and their salts, Monothio glycerol.

pH modifiers/ adjusting agents suitable are selected from sodium hydroxide, potassium hydroxide, hydrochloric acid carbonic acid, phosphoric acid, succinic acid, tartaric acid, lactic acid, and their sodium, potassium , calcium, ammonium salts.
Resin suitable are selected from AMBERLITE IRP-88, AMBERLITE IRP-64 (a porous copolymers of methacrylic acid crosslinked with divinylbenzene), KYRON T114 (Methacrylic acid copolymer crosslinked with divenyl benzene), TULSION 335, INDION 234, INDION 264 (cross-linked acrylic polymer).
Stabilizers are selected from EDTA disodium salt, amino acids such as glutamic acid.
Viscosity modifiers are selected from methylcellulose, sodium carboxy methylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, sodium alginate, carbomer, povidone, Acacia, Guar gum, Xanthan gum, Tragacanth, crosscaremellose sodium, macrocrystalline cellulose, ethyl cellulose, magnesium aluminum silicate.
Preservatives are selected from phenol, sorbic acid, benzoic acid, potassium sorbate, sodium benzoate, benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, sodium salts of methyl paraben, propyl paraben, butyl paraben.
Sweeteners are selected from sucrose, invert syrup, glucose, saccharin, sodium saccharin, sorbitol, malt extract, mannitol, xylitol, aspartame, sucralose.
Anti caking agent is selected from colloidal silicon dioxide.
Colours and flavoring agent suitable are selected from synthetic and natural agent of pharmaceutical grade.
Liquid oral pharmaceutical composition of the invention does not contain pharmaceutical excipients such as ethanol, buffer salt, non ionic water soluble polymer derived from cellulose (Hydroxyethyl cellulose), LCMT sucrose and polyethylene glycol which are reported in prior art to improve the stability of ranitidine in liquid compositions.

The compositions as per the present invention comprise following ingredients.
Table 1: Composition as per the invention

S.No. Ingredient
1. Ranitidine Hydrochloride
2. Co-solvent
3. Anti oxidants
4. Ion exchange resin
5. pH modifier/adjusting agent
6 Aqueous vehicle: water
Preparation of Compositions of the Present Invention
In preferred embodiment the composition is prepared by dispersing ion exchange resin in water. Then dissolving the drug into water and mixing with ion exchange resin slurry. Further, pH of the slurry is adjusted to 6.5 with pH modifying agent and is stirred for 6 to 8 hours. Then dissolving the antioxidants into co-solvent and mixing with ion exchange resin slurry containing drug.
Table 2: Composition as per the invention

S.No. Ingredient
1. Ranitidine Hydrochloride
2. Co-solvent
3. Anti oxidants
4. Ion exchange resin
5. pH modifier/adjusting agent
6. Aqueous vehicle: water
7. Preservatives
In another embodiment the composition is prepared by dissolving drug into water and adding ion exchange resin to drug solution. Further, pH of the slurry is adjusted to 6.5 with pH modifying agent and is stirred for 6 to 8 hours. Then dissolving the antioxidants, preservatives into co-solvent and mixing with ion exchange resin slurry containing drug.

Table 3: Composition as per the invention

S.No. Ingredient
1. Ranitidine Hydrochloride
2. Co-solvent
3. Anti oxidants
4. Ion exchange resin
5. pH modifier/ adjusting agent
6. Aqueous vehicle: water
7. Preservatives
8. Viscosity modifier
In another embodiment the composition is prepared by dispersing ion exchange resin in water. Then dissolving the drug into water and mixing with ion exchange resin slurry. Further, pH of the slurry is adjusted to 6.5 with pH modifying agent and is stirred for 6 to 8 hours. Thereafter, antioxidants, preservatives, viscosity modifier are dissolved in co-solvent and then mixed with ion exchange resin slurry containing drug.
Table 4: Composition as per the invention

S.No. Ingredient
1. Ranitidine Hydrochloride
2. Co-solvent
3. Anti oxidants
4. Ion exchange resin
5. pH modifier/ adjusting agent
6. Aqueous vehicle: water
7. Preservatives
8. Viscosity modifier
9. Stabilizer
In another embodiment the composition is prepared by dispersing ion exchange resin in water. Then dissolving the drug into water and mixing with ion exchange resin slurry. Further, pH of the slurry is adjusted to 6.5 with pH modifying agent and is stirred for 6 to 8 hours. Thereafter,

antioxidants, preservatives, viscosity modifier, stabilizers are dissolved in co-solvent and then mixed with ion exchange resin slurry containing drug.
Table 5: Composition as per the invention

S.No. Ingredient
1. Ranitidine Hydrochloride
2. Co-solvent
3. Anti oxidants
4. Ion exchange resin
5. pH modifier/adjusting agent
6. Aqueous vehicle: water
7. Preservatives
8. Viscosity modifier
9. Stabilizer
10. Sweetener
In another embodiment the composition is prepared by dissolving drug into water and adding ion exchange resin to drug solution. Further, pH of the slurry is adjusted to 6.5 with pH modifying agent and is stirred for 6 to 8 hours. Then, dissolving the antioxidants, preservatives, viscosity modifier, stabilizers, sweetener into co-solvent and mixing with ion exchange resin slurry containing drug.
Table 6: Composition as per the invention

S.No. Ingredient
1. Ranitidine Hydrochloride
2. Co-solvent
3. Anti oxidants
4. Ion exchange resin
5. pH modifier / adjusting agent
6. Aqueous vehicle: water
7. Preservatives
8. Viscosity modifier

9. Stabilizer
10. Sweetener
11. Anticaking agent
In another embodiment the composition is prepared by dissolving drug into water and adding ion exchange resin to drug solution. Further, pH of the slurry is adjusted to 6.5 with pH modifying agent and is stirred for 6 to 8 hours. Then dissolving the antioxidants, preservatives, viscosity modifier, stabilizers, sweetener and Anticaking agent into co-solvent and mixing with ion exchange resin slurry containing drug.
Table 7: Composition as per the invention

S.No. Ingredient
1. Ranitidine Hydrochloride
2. Co-solvent
3. Anti oxidants
4. Ion exchange resin
5. pH modifier/ adjusting agent
6. Aqueous vehicle: water
7. Preservatives
8. Viscosity modifier
9. Stabilizer
10. Sweetener
11. Anticaking agent
12. Colour and flavor
In another embodiment the composition is prepared by dissolving drug into water and adding ion exchange resin to drug solution. Further, pH of the slurry is adjusted to 6.5 with pH modifying agent and is stirred for 6 to 8 hours. Then dissolving the antioxidants, preservatives, viscosity modifier, stabilizers, sweetener, Anticaking agent, colour and flavour into co-solvent and mixing with ion exchange resin slurry containing drug.

The invention is illustrated with the non-limiting examples
Example 1
Table 8: Composition of example 1

S.No Ingredients Category Quantity
1. Ranitidine hydrochloride Active Pharmaceutical Ingredient 11.27 gm
2. Glycerin Co-solvent 300.00 gm
3. Sorbitol solution 70% w/w Co-solvent 100.00 gm
4. Butylated hydroxy anisole Anti oxidant 0.10 gm
5. Butylated Hydroxy Toluene Anti oxidant 0.10 gm
6. KyronT114 Ion exchange resin 39.43 gm
7. Potassium Hydroxide pH modifier 13.0 gm
8. Methyl paraben sodium Preservative 2.00 gm
9. Propyl paraben sodium Preservative 0.20 gm.
10. Disodium EDTA Stabilizer 3.00 gm
11. Colloidal silicon dioxide Anticaking agent 2.00 gm
12. Sucralose Sweetener 4.00 gm
13. Xanthan gum Viscosity modifier 4.00 gm
14. Colour Colour 40.00 mg
15. Flavour Sweet orange Flavour 2.00 ml
16. Purified water Vehicle 1000 ml
Method of preparation
1. Dispersing the weak cation ion-exchange resin in 80 ml of water. Ranitidine hydrochloride was dissolved in 50 ml of purified water and mixed with resin slurry. Then pH was adjusted to 6.5 with 20% potassium hydroxide solution and mixed for 6 to 8 hours;
2. Glycerin was transferred into a mixing vessel and heated to 70 to 80°C;
3. Butylated hydroxy anisole and Butylated hydroxy toluene were dissolved in hot glycerin in the mixing vessel. The whole content was cooled to room temperature;
4. Xanthan gum was transferred in to the mixing vessel of step 3 and mixed ;
5. Sorbitol was added to the mixing vessel and mixed.
6. EDTA was dissolved in purified water and transferred into the mixing vessel and mixed;
7. Methyl paraben sodium and propyl paraben sodium were dissolved in water and added in to the mixing vessel and mixed;
8. Colloidal silicon dioxide was added into the mixing vessel and mixed;

9. Drug-resin complex slurry of step -1 was transferred into the mixing vessel and mixed;
10. Sucralose was dissolved in water and transferred into the mixing vessel;
11. Colour was dissolved in water and added into the mixing vessel and mixed;
12. Flavour was added into the mixing vessel and mixed and;
13. pH of the final solution is adjusted to 7.2 with 20% Potassium Hydroxide solution.
Example 2
Table 9: Composition of example 2

S.No Ingredients Category Quantity
1. Ranitidine hydrochloride Active Pharmaceutical Ingredient 84.00 gm
2. Sorbitol solution 70% w/w Co-solvent 1500.0 gm
3. Sodium Metabisulphite Antioxidant 1.50 gm
4. KyronT114 Ion exchange resin 252.00 gm
5. Potassium Hydroxide pH modifier 20.0 gm
6. Methyl paraben sodium Preservative 5.00 gm
7. Propyl paraben sodium Preservative 0.50 gm.
8. Disodium EDTA Stabilizer 1.50 gm
9. Xanthan gum Viscosity modifier 12.50 gm
10. Sucralose Sweetener 12.50 gm
11. Colour Colour 0.50 gm
12. Menthol Flavour 0.50 gm
13. Flavour Peppermint Flavour 4.00 ml
14. Purified water Vehicle 5000 ml.
Method of Preparation
1. Kyron T114 was dispersed in 700 ml of purified water and mixed. Ranitidine hydrochloride was added into resin slurry with mixing and pH was adjusted to 6.5 with 20% potassium hydroxide solution and mixed for 3-4 hours;
2. Sorbitol was transferred into the mixing vessel;
3. Propyl paraben Sodium, Methyl paraben sodium, disodium EDTA salt, sodium metabisulphite were dissolved in Sorbitol solution;
4. Xanthan gum was dispersed in hot purified water and transferred into the mixing vessel and mixed;
5. Drug resin complex was transferred into the mixing vessel and mixed;
6. Sucralose was dissolved in purified water and transferred into the mixing vessel and mixed;

7. Colour was dissolved into the purified water and transferred into the mixing vessel and mixed;
8. Menthol and Flavoring agent were added into the mixing vessel and mixed and;
9. pH of the final solution was adjusted to 7.5 with 20% Potassium hydroxide solution.
Example 3
Table 10: Composition of example 3

S.No Ingredients Category Quantity
1. Ranitidine hydrochloride Active Pharmaceutical Ingredient 84.00 gm
2. Sorbitol solution 70% w/w Co-solvent 500.0 gm
3. Glycerin Co-solvent 1500.0 gm
4. Sodium Metabisulphite Antioxidant 1.50 gm
5. Kyron T114 Ion exchange resin 252.00 gm
6. Potassium Hydroxide pH modifier 20.0 gm
7. Methyl paraben sodium Preservative 5.00 gm
8. Propyl paraben sodium Preservative 0.50 gm.
9. Disodium EDTA Stabilizer 1.50 gm
10. Xanthan gum Viscosity modifier 10.00 gm
11. Sucralose Sweetener 12.50 gm
12. Colour Colour 0.50 gm
13. Menthol Flavour 0.50 gm
14. Flavour Mixed Fruit Flavour 3.00 ml
15. Purified water Vehicle 5000 ml.
Method of Preparation
1. Kyron T114 was dispersed in 700 ml of purified water and mixed. Ranitidine hydrochloride was added into resin slurry with mixing and pH was adjusted to 6.5 with 20% potassium hydroxide solution and mixed for 3-4 hours;
2. Sorbitol and glycerin were transferred into the mixing vessel;
3. Propyl paraben sodium, methyl paraben sodium, disodium EDTA salt, sodium metabisulphite were added to the mixing vessel;
4. Xanthan gum was dispersed in hot purified water and transferred into the mixing vessel and mixed;
5. Drug resin complex was transferred into the mixing vessel and mixed;
6. Sucralose was dissolved in purified water and transferred into the mixing vessel and mixed;

7. Colour was dissolved into the purified water and transferred into the mixing vessel and mixed;
8. Menthol and Flavoring agent were added into the mixing vessel and mixed and;
9. pH of the final solution was adjusted to 7.0 with 20% Potassium hydroxide solution.
Example 4
Table 11: Composition of example 4

S.No Ingredients Category Quantity
1. Ranitidine hydrochloride Active Pharmaceutical Ingredient 27.80 gm
2. Sorbitol solution 70% w/w Co-solvent 500.0 gm
3. Glycerin Co-solvent 2000.0 gm
4. Sodium Metabisulphite Antioxidant 1.50 gm
5. KyronT114 Ion exchange resin 84.00 gm
6. Potassium Hydroxide pH modifier 15.0 gm
7. Methyl paraben sodium Preservative 5.00 gm
8. Propyl paraben sodium Preservative 0.50 gm.
9. Disodium EDTA Stabilizer 1.50 gm
10. Xanthan gum Viscosity modifier 10.00 gm
11. Sucralose Sweetener 12.50 gm
12. Colour Colour 0.50 gm
13. Flavour Mixed fruit Flavour 0.50 gm
14. Flavour Pineapple Flavour 3.00 ml
15. Purified water Vehicle 5000 ml.
Method of Preparation
1. Kyron T114 was dispersed in 700 ml of purified water and mixed. Ranitidine hydrochloride was added into resin slurry with mixing and pH was adjusted to 6.5 with 20% potassium hydroxide solution and mixed for 3-4 hours;
2. Sorbitol and glycerin were transferred into the mixing vessel;
3. Propyl paraben sodium, Methyl paraben sodium, disodium EDTA salt, sodium metabisuiphite were added to mixing vessel.
4. Xanthan gum was dispersed in hot purified water and transferred into the mixing vessel and mixed;
5. Drug resin complex was transferred into the mixing vessel and mixed;
6. Sucralose was dissolved in purified water and transferred into the mixing vessel and mixed;

7. Colour was dissolved into the purified water and transferred into the mixing vessel and mixed;
8. Flavoring agent were added into the mixing vessel and mixed and;
9. pH of the final solution was adjusted to 7.3 with 20% Potassium hydroxide solution.
Example 5
Table 12: Composition of example 5

S.No Ingredients Category Quantity
1. Ranitidine hydrochloride Active Pharmaceutical Ingredient 84.00 gm
2. Sorbitol solution 70% w/w Co-solvent 250.0 gm
3. Glycerin Co-solvent 2000.0 gm
4. Butylated Hydroxy Toluene Antioxidant 0.10gm
5. Kyron T114 Ion exchange resin 294.00 gm
6. Potassium Hydroxide pH modifier 20.0 gm
7. Methyl paraben sodium Preservative 5.00 gm
8. Propyl paraben sodium Preservative 0.50 gm.
9. Disodium EDTA Stabilizer 1.50 gm
10. Xanthan gum Viscosity modifier 10.00 gm
11. Sucralose Sweetener 15.00 gm
12. Colour Colour 0.50 gm
13. Flavour Pineapple Flavour 0.50 gm
14. Flavour Vanilla Flavour 3.00 ml
15. Purified water Vehicle 5000 ml.
Method of Preparation
1. Kyron T114 was dispersed in 700 ml of purified water and mixed. Ranitidine hydrochloride was added into resin slurry with mixing and pH was adjusted to 6.5 with 20% potassium hydroxide solution and mixed for 3-4 hours;
2. Sorbitol and glycerin were transferred into the mixing vessel;
3. Propyl paraben sodium, Methyl paraben sodium, disodium EDTA salt, butylated hydroxy toluene was added to mixing vessel.
4. Xanthan gum was dispersed in hot purified water and transferred into the mixing vessel and mixed;
5. Drug resin complex was transferred into the mixing vessel and mixed;
6. Sucralose was dissolved in purified water and transferred into the mixing vessel and mixed;

7. Colour was dissolved into the purified water and transferred into the mixing vessel and mixed;
8. Flavoring agent were added into the mixing vessel and mixed and;
9. pH of the final solution was adjusted to 7.1 with 20% Potassium hydroxide solution.
Example 6
Table 13: Composition of example 6

S.No Ingredients Category Quantity
1. Ranitidine hydrochloride Active Pharmaceutical Ingredient 84.00 gm
2. Glycerin Co-solvent 2000.00 gm
3. Butylated Hydroxy Toluene Antioxidant 0.10 gm
4. KyronT114 Ion exchange resin 294.00 gm
5. Potassium Hydroxide pH modifier 20.0 gm
6. Methyl paraben sodium Preservative 5.00 gm
7. Propyl paraben sodium Preservative 0,50 gm
8. Disodium EDTA Stabilizer 1.50 gm
9. Xanthan gum Viscosity modifier 10.00 gm
10. Sucralose Sweetener 15.00 gm
11. Colour Colour 0.50 gm
12. Menthol Flavour 0.50 gm
13. Flavour Sweet orange Flavour 3.00 ml
14. Purified water Vehicle 5000 ml.
Method of Preparation
1. Kyron T114 was dispersed in 700 ml of purified water and mixed. Ranitidine hydrochloride was added into resin slurry with mixing and pH was adjusted to 6.5 with 20% potassium hydroxide solution and mixed for 3-4 hours;
2. Glycerin was transferred into the mixing vessel;
3. Propyl paraben Sodium, Methyl paraben sodium, disodium EDTA salt, butylated hydroxy toluene were dissolved in glycerin solution;
4. Xanthan gum was transferred into the mixing vessel and mixed;
5. Drug resin complex was transferred into the mixing vessel and mixed;
6. Sucralose was dissolved in purified water and transferred into the mixing vessel and mixed;
7. Colour was dissolved into the purified water and transferred into the mixing vessel and mixed;

8. Menthol and Flavoring agent were added into the mixing vessel and mixed and;
9. pH of the final solution was adjusted to 7.2 with 20% Potassium hydroxide solution.
Example 7
Table 14: Composition of example 7

S.No Ingredients Category Quantity
1. Ranitidine hydrochloride Active Pharmaceutical Ingredient 84.00 gm
2. Glycerin Co-solvent 2500.0 gm
3. Butylated Hydroxy Toluene Antioxidant 0.10 gm
4. Butylated Hydroxy Anisole Antioxidant 0.10 gm
5. Kyron T114 Ion exchange resin 294.00 gm
6. Potassium Hydroxide pH modifier 20.0 gm
7. Methyl paraben sodium Preservative 5.00 gm
8. Disodium EDTA Stabilizer 1.50 gm
9. Xanthan gum Viscosity modifier 10.00 gm
10. Sucralose Sweetener 15.00 gm
11. Colour Colour 0.50 gm
12. Flavour Toffee Flavour 0.50 gm
13. Flavour Peppermint Flavour 3.00 ml
14. Purified water Vehicle 5000 ml.
Method of Preparation
1. Kyron T114 was dispersed in 700 ml of purified water and mixed. Ranitidine hydrochloride was added into resin slurry with mixing and pH was adjusted to 6.5 with 20% potassium hydroxide solution and mixed for 3-4 hours;
2. Glycerin was transferred into the mixing vessel;
3. Methyl paraben sodium, disodium EDTA salt, butylated hydroxy toluene, butylated hydroxy anisole were dissolved in Glycerin solution;
4. Xanthan gum was transferred into the mixing vessel and mixed;
5. Drug resin complex was transferred into the mixing vessel and mixed;
6. Sucralose was dissolved in purified water and transferred into the mixing vessel and mixed;
7. Colour was dissolved into the purified water and transferred into the mixing vessel and mixed;
8. Flavoring agent were added into the mixing vessel and mixed and;

9. pH of the final solution was adjusted to 7.2 with 20% Potassium hydroxide solution.
The formulations from examples 1 were subjected to stability study at room temperature as shown in table 15.
Table 15: Stability data of composition of example 1 at 25° ± 2°C /60 % ± 5 % RH.

Test Specification Initial 3 months 6 months 9 months 12 months 18 months
Description Pink colored thick flavored suspension Complies Complies Complies Complies Complies Complies
PH Between 6.5 to 8.5 7.15 7.09 6.94 6.87 6.79 6.75
Assay 90.0% to 110.0%.
(135.0 mg to 165.0
mg/10 ml) 102.3% {153.5 mg) 99.1 % (148.7 mg) 99.8 % (149.7 mg) 98.4 % (147.6 mg) 98.8 % (148.2 mg) 98.0 % (147.0 mg)
Water content Not more than 50% 23% — — 18%
The oral liquid compositions as per the invention comprising ranitidine or its pharmaceutically acceptable salt, co-solvent (15 to 35% w/v), resin, antioxidant, water and pH modifier/adjusting agent are found to be stable up to 18 months at 25° ± 2°C /60 % ± 5 % RH.

We Claim:
1. A stable liquid oral pharmaceutical composition comprising ranitidine or its pharmaceutical acceptable salt, co-solvent, resin, antioxidant, water, pH modifier/adjusting agent.
2. The liquid oral pharmaceutical composition as claimed in claim 1 is stable for at least 18 months or more at 25°C.
3. The liquid oral pharmaceutical composition as claimed in claim 1 contains water content not more than 50%.
4. The liquid oral pharmaceutical composition as claimed in claim 1, wherein co-solvent is selected from glycerin, maltitol, sorbitol and propylene glycol, preferably glycerin.
5. The liquid oral pharmaceutical composition as claimed in claim 4, wherein glycerin is used in range of 15 to 50% w/v, preferably 20 to 40% w/v, most preferably 25 to 35% w/v.
6. The liquid oral pharmaceutical composition as claimed in claim 1 wherein the resin is selected from the group of AMBERLITE IRP-88, AMBERLITE IRP-64 (a porous copolymers of methacrylic acid crosslinked with divinylbenzene), KYRON T114 (Methacrylic acid copolymer crosslinked with divenyl benzene), TULSION 335, INDION 234, INDION 264 (cross-linked acrylic polymer).
7. The liquid oral pharmaceutical composition as claimed in claim 1, wherein the antioxidant is selected from the group of butylated hydroxy anisole, butylated hydroxy toluene, sodium metabisulfite, propyl gallate, l-cysteine hydrochloride, vitamin E acetate, ascorbic acids and their salts, monothio glycerol.
8. The liquid oral pharmaceutical composition as claimed in claim 1, wherein pH modifier/adjusting agent is selected from the group of sodium hydroxide, potassium hydroxide, hydrochloric acid carbonic acid, phosphoric acid, succinic acid, tartaric acid, lactic acid, and their sodium, potassium , calcium, ammonium salts.
9. The liquid oral pharmaceutical composition as claimed in claim 1 further comprising one or more pharmaceutical excipients selected from viscosity modifiers, preservatives, sweetening agents, stabilizers, anti-caking agents, pharmaceutical-grade dyes/pigments and flavoring agent.
10. The liquid oral pharmaceutical composition as claimed in claim 1 does not contain ethanol, buffer salt, non ionic water soluble polymer derived from cellulose (Hydroxyethyl cellulose), LCMT sucrose and polyethylene glycol.

11. The liquid oral pharmaceutical composition as claimed in claim 9, wherein the viscosity modifier is selected from the group of methylcellulose, sodium carboxy methylcellulose, hydroxy propyl methylcellulose, hydroxy propyl cellulose, sodium alginate, carbomer, povidone, Acacia, Guar gum, xanthan gum, tragacanth, crosscaremellose sodium, microcrystalline cellulose, ethyl cellulose and magnesium aluminum silicate.
12. The. liquid oral pharmaceutical composition as claimed in claim 9, wherein the preservative is selected from the group of phenol, sorbic acid, benzoic acid, potassium sorbate, sodium benzoate, benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, sodium salts of methyl paraben, propyl paraben and butyl paraben.
13. The liquid oral pharmaceutical composition as claimed in claim 9, wherein the sweetener is selected from the group of invert syrup, glucose, saccharin, sodium saccharin, sorbitol, malt extract, mannitol, xylitol and aspartame,
14. The liquid oral pharmaceutical composition as claimed in claim 9, wherein the stabilizer is selected from the group of EDTA disodium salt.
15. The liquid oral pharmaceutical composition as claimed in claim 1-14 is in the form of syrup, suspension, liquid solution and like.