FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition in the form of suspension and suspension powder for reconstitution of valsartan suitable for oral administration. It also relates to a process for the preparation of said compositions.
BACKGROUND OF THE INVENTION
Valsartan, an angiotensin II receptor antagonist, is widely used in the treatment of hypertension and congestive heart failure. It is commercially available as a tablet and capsule under the brand name Diovan® by Novartis. However, tablet and capsule dosage forms are difficult to swallow by children and geriatric patients. This may lead to non-compliance due to chronic nature of the therapy. Therefore, liquid formulations of valsartan are desirable.
U.S. Publication Nos. 20100267787 and 20130109729 disclose aqueous solutions of valsartan comprising water and valsartan.
U.S. Publication No. 20130102594 discloses a suspension which is extemporaneously prepared from valsartan tablets (Diovan®). To prepare the suspension, Diovan® tablets are added to a dispensing bottle and Ora-Plus™ Suspending Vehicle is added to the bottle and shaken subsequently. The suspension is then allowed to stand for at least 1 hour. After the standing time, the suspension is shaken. After shaking, Ora-Sweet™ SF Syrup Vehicle is added to the bottle. The final extemporaneous suspension is shaken to disperse the ingredients. The disclosed process for the preparation of valsartan suspension is tedious and cumbersome and is prone to errors which may lead to overdosing or under dosing of the active ingredient. Further, stability issues may arise during storage of the suspension.
There exists a need in the art for ready to use suspension and suspension powder for reconstitution of valsartan suitable for oral administration for enhanced patient compliance. The inventors of the present invention provide ready to use suspension

and suspension powder for reconstitution of valsartan which are convenient for administration by pediatric and geriatric patients, easy to manufacture, functionally reproducible, and provide ease of strength adjustment. Further, the suspension exhibits desirable technical attributes like pourability, viscosity, release profile, and re-suspendability.
SUMMARY OF THE INVENTION
The present invention relates to a pharmaceutical composition in the form of suspension and suspension powder for reconstitution of valsartan suitable for oral administration. It also relates to a process for the preparation of said compositions. Said suspension provides high level of patient compliance, and allow for dosing flexibility based on age and body weight of the patients.
One embodiment of the present invention relates to an oral suspension dosage form of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph and one or more pharmaceutically acceptable excipients and/or a carrier.
Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph and one or more pharmaceutically acceptable excipients. The suspension powder for reconstitution can be reconstituted into a suspension with a carrier.
In yet another embodiment of the present invention, the pharmaceutically acceptable excipients and/or carrier are selected from the group comprising one or more of suspending agent, anticaking agent, antifoaming agent, pH adjusting agent, coloring agent, sweetening agent, flavoring agent, surfactant or wetting agent, buffer, diluent, preservative, and antioxidant.
According to another embodiment of the present invention, the suspension has a pH in a range of 3-7, particularly in the range of 3-6.

According to another embodiment of the present invention, the suspension powder for reconstitution after reconstitution with a carrier into a suspension has a pH in a range of 3-7, particularly in the range of 3-6.
According to another embodiment of the present invention, the amount of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph in the suspension ranges from about 0.1 mg/ml to about 100 mg/ml.
Another embodiment of the present invention relates to an oral suspension dosage form of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph from about 0.1 mg/mL to about 100 mg/mL and one or more pharmaceutically acceptable excipients and/or a carrier, wherein the pH of the suspension is from 3-6 and the sedimentation ratio of more than about 0.8 for at least 12 hours after the suspension powder for reconstitution is reconstituted into a suspension.
According to another embodiment of the present invention, the suspension and the suspension powder for reconstitution after reconstitution with a carrier into a suspension has a viscosity in the range of 100 to 3000 cP at 25°C. More particularly, the viscosity is in the range of 200 to 1400 cP at 25°C, much more particularly, the viscosity is in the range of 200 to 1100 cP at 25°C.
Another embodiment of the present invention relates to a suspension and/or suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph comprising:
a) a suspending agent;
b) a diluent and/or sweetening agent;
c) a preservative;
d) optionally an antioxidant;
e) pH adjusting agent to maintain the pH of the composition in the range of about 3 to about 6; and / or a carrier

Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph from about 0.01% to about. 10% by weight on the basis of the total weight of the composition which exhibits in-vitro dissolution rate not less than 80% of drug release within 30 minutes when placed in a dissolution vessel filled with 1000 ml of phosphate buffer (pH 6.8) maintained at 37±0.5°C and stirred at a paddle speed of 50 rpm using a USP Type II (paddle) apparatus.
Another embodiment of the present invention relates to a suspension of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared by a process comprising the following steps:
i. dissolving/dispersing one or more pharmaceutically acceptable
excipients in a portion of water; ii. dispersing valsartan in the solution of step (i) to form a dispersion iii. mixing viscosity agent in another portion of water; iv. adding the mixture of step (iii) to the dispersion of step (ii); v. optionally adding one or more pharmaceutically acceptable
excipients to the dispersion of step (iv); and vi. optionally homogenizing the mixture of step (iv) to form a
suspension.
Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared using dry granulation, wet granulation and blending processes.
Another embodiment of the present invention relates to a method of treating cardiovascular disease by administering a suspension or suspension powder for reconstitution of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph and one or more pharmaceutically acceptable excipient and/or a carrier.

According to one embodiment of the above aspect, the cardiovascular disease is selected from the group comprising hypertension, congestive heart failure, angina, myocardial infarction, arteriosclerosis, peripheral vascular disease, stroke, left ventricular hypertrophy, cognitive dysfunction, diabetic nephropathy, diabetic cardiac myopathy, renal insufficiency, headache, and or chronic heart failure.
According to another embodiment of the above aspect, the composition further comprises one or more cardiovascular drugs selected from the group comprising antihypertensives, diuretics, and combinations thereof
DETAILED DESCRIPTION OF THE INVENTION
The pharmaceutical composition of the present invention is directed to ready to use oral liquid suspension and suspension powder for reconstitution suitable for use as a liquid suspension.
As used herein, the term "composition or "formulation" or "dosage form", as in pharmaceutical composition, is intended to encompass a drug product comprising antihypertensive drug, preferably valsartan or its pharmaceutically acceptable salts, esters, solvates, polymorphs, enantiomers or mixtures thereof, and other inert ingredient(s) (pharmaceutically acceptable excipients). Such pharmaceutical compositions are synonymous with "formulation" and "dosage form". Pharmaceutical composition of the invention include, but is not limited to, solution, powder for suspension, oral suspension and the like. Preferably, the pharmaceutical composition refers to suspension. More preferably, the pharmaceutical composition refers to ready to use suspension or suspension powder for reconstitution. Suspension powder for reconstitution comprises granules, pellets, beads, spheroids, flakes or blend of valsartan with one or more pharmaceutically acceptable excipients. Suspension powder for reconstitution is dry and flowable.
The term "valsartan," as used herein includes valsartan and its salts, polymorphs, hydrates, solvates, prodrugs, chelates, esters, derivatives, analogs, enantiomers, and

complexes. The pharmaceutical suspension of the present invention comprises valsartan in an amount from about 0.01% w/w to about 95% w/w of the total composition, particularly in an amount from about 0.01% to about 50% w/w of the total composition, particularly in an amount from about 0.01% to about 10% w/w of the total composition, particularly in an amount from about 0.01% to about 5% w/w of the total composition.
As used herein, the term "ready to use suspension or suspension" means a preconstituted suspension which can be administered as such. The "suspension powder for reconstitution", "powder for suspension" or "dry suspension" needs to be reconstituted with a liquid carrier to form a suspension.
As used herein, the term "sedimentation volume ratio" is the ratio of the ultimate volume of sediment to the original volume of sediment before settling.
The term "about," as used herein, refers to ± 20% of the indicated value.
One embodiment of the present invention relates to an oral suspension dosage form of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph and one or more pharmaceutically acceptable excipients and/or a carrier.
Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph and one or more pharmaceutically acceptable excipients. The suspension powder for reconstitution can be reconstituted into a suspension with a carrier.
In yet another embodiment of the present invention, the pharmaceutically acceptable excipient and/or carrier are selected from the group comprising one or more of suspending agent, anticaking agent, antifoaming agent, pH adjusting agent,

coloring agent, sweetening agent, flavoring agent, surfactant or wetting agent, buffer, diluent, preservative, and antioxidant.
According to another embodiment of the present invention, the suspension has a pH in a range of 3-7, particularly in the range of 3-6.
According to another embodiment of the present invention, the suspension powder for reconstitution after reconstitution with a carrier into a suspension has a pH in a range of 3-7, particularly in the range of 3-6.
According to another embodiment of the present invention, the amount of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph in the suspension ranges from about 0.1 mg/ml to about 100 mg/ml, particularly from 1 mg/ml to about 100 mg/ml, particularly from 1 mg/ml to about 75 mg/ml, particularly from 1 mg/ml to about 50 mg/ml and particularly from 1 mg/ml to about 25 mg/ml.
Another embodiment of the present invention relates to an oral suspension dosage form of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph from about 0.1 mg/mL to about 100 mg/mL and one or more pharmaceutically acceptable excipients and/or a carrier, wherein the pH of the suspension is from 3-6 and the sedimentation ratio of more than about 0.8 for at least 12 hours after the suspension powder for reconstitution is reconstituted into a suspension.
According to another embodiment of the present invention, the suspension and the suspension powder for reconstitution after reconstitution with a carrier into a suspension has a viscosity in the range of 100 to 3000 cP at 25°C. More particularly, the viscosity is in the range of 200 to 1400 cP at 25°C, much more particularly, the viscosity is in the range of 200 to 1100 cP at 25°C.
Another embodiment of the present invention relates to an oral suspension dosage form of valsartan comprising valsartan or its pharmaceutically acceptable salt,

hydrate or polymorph from about 0.1 mg/mL to about 100 mg/mL and one or more pharmaceutically acceptable excipients and/or a carrier wherein the pH of the suspension is from 3-6 and viscosity from 200-1400 cP.
According to another embodiment of the present invention, the suspension powder for reconstitution comprises from about 0.1 mg/mL to about 100 mg/mL valsartan or its pharmaceutically acceptable salt, hydrate or polymorph; from about 0.1 to 10.0% a suspending agent; from about 40 to 98% sucrose; an effective amount of pH adjusting agent, sweetening agent and/or preservative.
According to another embodiment of the present invention, the suspension powder for reconstitution of valsartan comprise from about 0.1 mg/mL to about 100 mg/mL valsartan or its pharmaceutically acceptable salt, hydrate or polymorph; from about 0.1 to 10.0% a suspending agent; from about 40 to 98% sucrose; and a pH adjusting agent.
Another embodiment of the present invention relates' to a suspension and/or suspension powder for reconstitution of valsartan comprising:
a) valsartan or its pharmaceutically acceptable salt, hydrate or polymorph;
b) a suspending agent;
c) a diluent and/or sweetening agent;
d) a preservative;
e) optionally an antioxidant;
f) pH adjusting agent to maintain the pH of the composition in the range of about 3 to about 6; and / or a carrier
Another embodiment of the present invention relates to a suspension and/or suspension powder for reconstitution of valsartan comprising:
a) valsartan or its pharmaceutically acceptable salt, hydrate or polymorph;

b) a suspending agent selected from gums and/or celluloses and their derivatives;
c) a diluent and/or sweetening agent selected from sugars and sugar alcohols;
d) a preservative;
e) optionally an antioxidant;
f) pH adjusting agent to maintain the pH of the composition in the range of about 3 to about 6; and / or a carrier
Another embodiment of the present invention relates to a suspension and/or suspension powder for reconstitution of valsartan comprising:
a) valsartan or its pharmaceutically acceptable salt, hydrate or polymorph;
b) a suspending agent from about 0.05% w/w to about 20% w/w;
c) a diluent from about 5% w/w to about 98% w/w;
d) a preservative;
e) optionally an antioxidant;
f) pH adjusting agent to maintain the pH of the composition in the range of about 3 to about 6; and / or a carrier.
Another embodiment of the present invention relates to a suspension and/or suspension powder for reconstitution of valsartan comprising:
a) valsartan or its pharmaceutically acceptable salt, hydrate or polymorph
b) a suspending agent from about 0.05% w/w to about 20% w/w;
c) a diluent from about 5% w/w to about 98% w/w;
d) pH adjusting agent to maintain the pH of the composition in the range of about 3 to about 6; and / or a carrier.
In yet another embodiment, the suspension and/or suspension powder for reconstitution of valsartan further comprises a preservative and optionally an antioxidant.

Another embodiment of the present invention relates to a suspension and/ suspension powder for reconstitution comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph, wherein the suspending agent is selected from the group comprising cellulose derivatives such as co-processed spray dried forms of microcrystalline cellulose and carboxymethyl cellulose sodium, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methylcellulose, carboxymethyl cellulose and its salts/derivatives, and microcrystalline cellulose; gums and their derivatives such as alginic acid, propylene glycol alginate, locust bean gum, xanthan gum, tragacanth gum, arabinogalactan gum, agar gum, gellan gum, guar gum, apricot gum, karaya gum, sterculia gum, acacia gum, gum arabic, and carrageenan; carbomers;pectin; 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 co-processed spray dried forms of microcrystalline cellulose and carboxymethyl cellulose sodium have been marketed under the trade names Avicel® RC-501, Avicel® RC-581, Avicel® RC-591, and Avicel®CL-611.
Another embodiment of the present invention relates to a suspension and/ suspension powder for reconstitution comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph, wherein the suspending agent is selected from xanthan gum, carboxymethyl cellulose sodium, propylene glycol alginate and combinations thereof.
Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph from about 0.01% to about 10% by weight on the basis of the total weight of the composition which exhibits in-vitro dissolution rate not less than 80% of drug release within 30 minutes when placed in a dissolution vessel

filled with 1000 ml of phosphate buffer (pH 6.8) maintained at 37±0.5°C and stirred r
at a paddle speed of 50 rpm using a USP Type II (paddle) apparatus.
Another embodiment of the present invention relates to a suspension of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared by a process comprising the following steps:
i) dissolving/dispersing one or more pharmaceutically acceptable excipients
in a portion of water; ii) dispersing valsartan in the solution of step (i) to form a dispersion iii) mixing viscosity agent in another portion of water; iv) adding the mixture of step (iii) to the dispersion of step (ii); v) optionally adding one or more pharmaceutically acceptable excipients to the
dispersion of step (iv); and vi) optionally homogenizing the mixture of step (iv) to form a suspension.
Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared by a process comprising the following steps:
i) mixing valsartan with one or more pharmaceutically acceptable excipients;
ii) granulating the mixture of step (i) using a solvent;
iii) drying the granulated mixture of step (ii);
iv) milling the mixture of step (iii) to form granules; and
v) mixing the granules of step (iv) optionally with one or pharmaceutically acceptable excipients to form the suspension powder for reconstitution Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared by a process comprising the following steps:
i) mixing valsartan with one or more pharmaceutically acceptable excipients; ii) compacting the mixture of step (i) to form slugs; iii) milling the slugs of step (ii) to form granules; and

iv) mixing the granules of step (iii) optionally with one or pharmaceutically acceptable excipients to form the suspension powder for reconstitution.
Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared by a process comprising the following steps:
i) mixing valsartan with one or more pharmaceutically acceptable excipients;
and ii) optionally lubricating the mixture of step (i) to form the suspension powder for reconstitution. Another embodiment of the present invention relates to a suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared using dry granulation by slugging or roller compaction, wet granulation and blending processes.
Another embodiment of the present invention relates to a method of treating cardiovascular disease by administering a suspension or suspension powder for reconstitution of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph and one or more pharmaceutically acceptable excipient and/or a carrier.
According to one embodiment of the above aspect, the cardiovascular disease is selected from the group comprising hypertension, congestive heart failure, angina, myocardial infarction, arteriosclerosis, peripheral vascular disease, stroke, left ventricular hypertrophy, cognitive dysfunction, diabetic nephropathy, diabetic cardiac myopathy, renal insufficiency, headache, and or chronic heart failure.

According to another embodiment of the above aspect, the composition further comprises one or more cardiovascular drugs selected from the group comprising antihypertensives, diuretics, and combinations thereof.
The term "pharmaceutically acceptable excipient," as used herein, refers to a pharmacologically inactive component that is useful in preparing a pharmaceutical composition. The pharmaceutically acceptable excipient may comprise a suspending agent, anticaking agent, antifoaming agent, pH adjusting agent, coloring agent, sweetening agent, flavoring agent, surfactant/wetting agent, buffer, diluent, preservative, antioxidant, stabilizer, and combinations thereof The excipients that are useful in preparing a pharmaceutical composition are generally safe, non-toxic and are acceptable for veterinary as well as human pharmaceutical use. Further, the excipient may be in the form of powder, solution, or in the form of dispersion.
Suitable suspending agents are selected from the group comprising cellulose derivatives such as co-processed spray dried forms of microcrystalline cellulose and carboxymethyl cellulose sodium, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methylcellulose, carboxymethyl cellulose and its salts/derivatives, and microcrystalline cellulose; gums and their derivatives such as alginic acid, propylene glycol alginate, locust bean gum, xanthan gum, tragacanth gum, arabinogalactan gum, agar gum, gellan gum, guar gum, apricot gum, karaya gum, sterculia gum, acacia gum, gum arabic, and carrageenan; carbomers;pectin; 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 co-processed spray dried forms of microcrystalline cellulose and carboxymethyl cellulose sodium have been marketed under the trade names Avicel® RC-501, Avicel® RC-581, Avicel® RC-591, and Avicel®CL-611. Particularly, the suspending agent are selected from gums and/or celluloses and their derivatives. The suspending agents are present in an amount of about 0.05% to about 20% w/w of the composition. Particularly, the suspending agents are present in an amount of

about 0.1% to about 10% w/w of the composition. More particularly, the suspending agents are present in an amount of about 0.1% to about 5% w/w of the composition. Much more particularly, the suspending agents are present in an amount of about 0.1% to about 3% w/w of the composition.
Diluents or fillers are substances which usually provide bulk to the composition. Various useful fillers or diluents include, but are not limited to sugar and sugar alcohols such as sucrose, sorbitol, xylitol, erythritol, mannitol, dextrose, sucralose, fructose; 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; mannitol; microcrystalline cellulose; polydextrose; sodium alginate; and mixtures thereof. Particularly, diluent used is sucrose. The diluent is present in an amount of 5 to 98 % w/w of the total composition.
Sucrose has a particle size such that not less than 90% particles are below 200 (am. In particular, sucrose has a particle size such that not less than 90% particles are below 100 |im. This helps in achieving improved uniformity of the drug in the mixture.
Carrier/vehicle/solvent used in the suspension of the present invention include aqueous and non-aqueous carrier but are not limited to water, alcohol, polyethylene glycol, propylene glycol or glycerin buffers, oil, or combinations thereof. Oils include peanut oil, soy bean oil, corn oil, sesame oil, cottonseed oil, acetylated glycerides, ethyl oleate, mineral oil, fatty acid esters, mono- or di- fatty acid esters of polyethylene glycols, or glyceryl mono-oleate. 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-
r
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 carrier is present in an amount from about 30 w/w% to about 95 w/w%, particularly from about 50 w/w% to about 95 w/w%.
Anti-caking agents help to re suspend the ingredients suspended in the formulation. Suitable anti-caking agents are selected from the group comprising colloidal silicon dioxide, tribasic calcium phosphate, powdered cellulose, magnesium trisilicate, starch, or mixtures thereof.
Suitable antifoaming agents are selected from the group comprising simethicone.
The suspension of the present invention has a pH in a range of 3-7. Particulary, the pH of the suspension has a pH of about 3-6. In order to maintain the desired pH range pH adjusting agents/buffering agents are added. Suitable pH adjusting agents/buffering agents are selected from the group comprising citric acid, sodium citrate, sodium phosphate, potassium citrate, gluconic acid, lactic acid, acetic acid, sodium gluconate, sodium lactate, acetate buffer, sodium acetate, potassium citrate, sodium bicarbonate, potassium bicarbonate, sodium dihydrogen phosphate and potassium dihydrogen phosphate, and combinations thereof.
Suitable coloring agent are selected from the group comprising FD&C (Federal Food, Drug and Cosmetic Act) approved coloring agents; natural coloring agents; natural juice concentrates; pigments such as iron oxide, titanium dioxide, and zinc oxide; and combinations thereof.
Suitable sweetening agent are selected from the group comprising saccharine or its salts such as sodium, potassium, or calcium, cyclamate or its salt, aspartame, alitame, acesulfame or its salt, and stevioside.

Suitable flavoring agents are selected from the group comprising peppermint, grapefruit, orange, lime, lemon, mandarin, pineapple, strawberry, raspberry, mango, passion fruit, kiwi, apple, pear, peach, apricot, cherry, grape, banana, cranberry, blueberry, black currant, red currant, gooseberry, lingon berries, cumin, thyme, basil, camille, valerian, fennel, parsley, chamomile, tarragon, lavender, dill, bargamot, salvia, aloe vera balsam, spearmint, eucalyptus, and combinations thereof.
Suitable surfactant or wetting agents are selected from the group comprising anionic, cationic, nonionic, or zwitterionic surfactants, or combinations thereof. Suitable examples of wetting agents are sodium lauryl sulphate; cetrimide; polyethylene glycols; polyoxyethylene-polyoxypropylene block copolymers such as poloxamers; polyglycerin fatty acid esters such as decaglyceryl monolaurate and decaglyceryl monomyristate; sorbitan fatty acid esters such as sorbitan monostearate; polyoxyethylene sorbitan fatty acid ester such as polyoxyethylene sorbitan monooleate; polyethylene glycol fatty acid ester such as polyoxyethylene monostearate; polyoxyethylene alkyl ether such as polyoxyethylene lauryl ether; polyoxyethylene castor oil; and combinations thereof.
Suitable preservatives are selected from the group comprising parabens such as methyl paraben and propyl paraben; sodium benzoate; sorbates; and combinations thereof.
Suitable antioxidant are selected from the group comprising butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium metabisulfite, ascorbic acid, propyl gallate, thiourea, tocopherols, beta-carotene, and combinations thereof.
In the pharmaceutical suspension of the present invention valsartan has a particle size distribution D90 less than about 300 |im, particularly less than 200 |im, more

particularly less than 150 jim, and much more particularly less than 100 (im. The particle size of valsartan can be measured by suitable techniques such as laser light scattering (e.g. Malvern Light Scattering), coulter counter, microscopy, fraunhofer diffraction, and any other technique known in the art.
> The suspension can be prepared by combining various components using
conventional equipment such as an overhead stirrer, ultrasonifiers, mills,
homogenizers, manufacturing and heating tank with or without vacuum application
assembly known in the art or industry practice. This is followed by addition of liquid
carrier (aqueous and/or non-aqueous), suspending agent, anticaking agent,
antifoaming agent, sweetening agent, taste masking agent, antioxidant in any order
found suitable and the like. pH of the suspension is adjusted to desired value using
buffering agents. In general, the suspension of valsartan is prepared by uniformly
and intimately mixing the components in the liquid medium.
The suspension can be packaged in a suitable pack such as bottle e.g., amber colored polyethylene terephthalate (PET) bottle, glass bottle, high.density polyethylene (HDPE) bottle, low density polyethylene (LDPE) bottle, polypropylene (PP) bottle; packet; pouch; and sachet.
The suspensions of the present invention are homogenous and deliver the desired dose of valsartan in every use without any risk of overdosing or underdosing.
The invention may be further illustrated by the following examples, which are for illustrative purposes only and should not be construed as limiting the scope of the invention in any way.

EXAMPLES Example 1: Ready to use Valsartan Suspension
Procedure:
1. Sucrose, sorbitol and glycerine were added to purified water under continuous stirring.
2. Valsartan was dispersed in the mixture of step 1.
3. Xanthan gum, Carrageenan and Avicel RC 591 were added under continuous stirring in a portion of water.
4. Sodium saccharin, citric acid, mono sodium dibasic phosphate and sodium citrate were added under continuous stirring in another portion of water.
5. The mixture of step 3 and step 4 were added to the dispersion of step 2.
6. Methyl paraben and propyl paraben were dissolved in propylene glycol.
7. The mixture of step 6 was added to the dispersion of step 5 and homogenized and the volume was made up with water to form a suspension.
8. The suspension of step 7 was filled into a glass bottle.
The pH of the suspension was determined to be 3.63

Examples 2-4- Suspension Powder for Reconstitution
Procedure:
1. Valsartan and sucrose were sifted through #60 mesh and mixed.
2. Sodium saccharin, sodium benzoate, monobasic sodium phosphate, citric acid, and sodium citrate were co-sifted through #60 mesh and mixed.
3. Silicon dioxide, xanthan gum/ sodium carboxymethyl cellulose/propylene glycol alginate, banana flavour and cherry flavour were co-sifted through #60 mesh and mixed.
4. The mixture of step 1, 2 and 3 were blended in a blender.
5. The blend of step 4 was filled in a HDPE bottle.
Assay for Valsartan
The suspension powder for reconstitution of Examples 2-4 were reconstitution with water to give a strength of 4 mg/mL and were analysed for drug content by HPLC using Column: C8 (150 x 4.6) mm, 5|im, mobile phase: pH 6.8 buffer and methanol (35: 65), flow rate of 1 mL/minute at detection wavelength of 273 nm. The results are provided in Table 1.

pH data
The suspension powder for reconstitution of Examples 2-4 were reconstitution with water to give a strength of 4 mg/mL. pH values were determined using potentiometry using USP <791> and the results are reported in Table 1.
Viscosity data
The viscosity of the suspension powder for reconstitution of Examples 2-4 after reconstitution with water to give a strength of 4 mg/mL was determined by using Brookfield viscometer Model LV with spindle and rpm 30 at 25°C and the results are reported in Table 1.
Sedimentation volume ratio
The suspension powder for reconstitution of Examples 2-4 was reconstituted with water to give a strength of 4 mg/mL. 100 mL of the reconstituted suspension was kept for 24 hours at room temperature. Initial volume and final volume of sediment were noted after 24 hours (Table 1).
Re-suspendability
It is the ability to re-suspend the settled particles with a minimum amount of shaking after the reconstituted suspension has stood for 24 hours at room temperature. 5 mL of the reconstituted suspension (with water to give a strength of 4 mg/mL) of Examples 2-4 were poured into three tubes and stored for 24 hours at room temperature. At the end of the storage period, each tube was hand shaken to see to note the time for re-suspendability (Table 1).
Table 1- Assay, Viscosity, pH, Sedimentation Ratio and Re-suspendability for Valsartan Suspensions after Reconstitution

Dissolution Studies
The suspension powder for reconstitution of Examples 2-4 were evaluated for in-vitro valsartan release. The m-vitro dissolution was determined using a USP type II apparatus (Paddle) at 50 rpm in 1000 mL of phosphate buffer (pH 6.8) at 37±0.5°C. The results are represented in Table 2.
Table 2- Percentage (%) of the In-Vitro Valsartan Release in USP Type II apparatus at 50 rpm in 1000 mL of Phosphate Buffer (pH 6.8)

We Claim:
1. An oral suspension dosage form of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph from about 0.1 mg/mL to about 100 mg/mL and one or more pharmaceutically acceptable excipients and/or a carrier, wherein the pH of the suspension is from 3-6 and the sedimentation volume ratio of more than about 0.8 for at least 12 hours after the suspension powder for reconstitution is reconstituted into a suspension.
2. An oral suspension dosage form of valsartan suspension comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph from about 0.1 mg/mL to about 100 mg/mL and one or more pharmaceutically acceptable excipients and/or a carrier wherein the pH of the suspension is from 3-6 and viscosity from 200-1400 cP.
3. A suspension and/or suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph comprising:

a) valsartan or its pharmaceutically acceptable salt, hydrate or polymorph;
b) a suspending agent from about 0.05% w/w to about 20% w/w;
c) a diluent from about 5% w/w to about 98% w/w;
d) pH adjusting agent to maintain the pH of the composition in the range of about 3 to about 6; and / or a carrier.

4. The suspension and/or suspension powder for reconstitution of valsartan of claim 3, further comprising a preservative and optionally an antioxidant.
5. A suspension powder for reconstitution of valsartan comprising from about 0.1 mg/mL to about 100 mg/mL valsartan or its pharmaceutically acceptable salt, hydrate or polymorph; from about 0.1 to 10.0% a suspending agent; from about 40 to 98% sucrose; and a pH adjusting agent.

6. A suspension powder for reconstitution of valsartan comprising valsartan or its pharmaceutically acceptable salt, hydrate or polymorph from about 0.01% to about 10% by weight on the basis of the total weight of the composition which exhibits in-vitro dissolution rate not less than 80% of drug release within 30 minutes when placed in a dissolution vessel filled with 1000 ml of phosphate buffer (pH 6.8) maintained at 37±0.5°C and stirred at a paddle speed of 50 rpm using a USP Type II (paddle) apparatus.
7. A suspension of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared by a process comprising the following steps:
(i) dissolving/dispersing one or more pharmaceutically acceptable
excipients in a portion of water; (ii) dispersing valsartan in the solution of step (i) to form a dispersion; (iii) mixing suspending agent in another portion of water; (iv) adding the mixture of step (iii) to the dispersion of step (ii); (v) optionally adding one or more pharmaceutically acceptable excipients
to the dispersion of step (iv); and (vi) optionally homogenizing the mixture of step (iv) to form a suspension.
8. A suspension powder for reconstitution of valsartan or its pharmaceutically acceptable salt, hydrate or polymorph prepared by a process selected from the group comprising dry granulation, wet granulation and blending process.
9. The suspension and/or suspension powder for reconstitution of valsartan of preceding claims, wherein the pharmaceutically acceptable excipients are selected from the group comprising one or more of suspending agent, anticaking agent, antifoaming agent, pH adjusting agent, coloring agent, sweetening agent, flavoring agent, surfactant or wetting agent, buffer, diluent, preservative, and antioxidant.

10. The suspension and/or suspension powder for reconstitution of valsartan of claim 9, wherein the suspending agents are selected from the group comprising cellulose derivatives, gums and their derivatives, carbomers, pectin, dextran, gelatin, polyethylene glycols, polyvinyl compounds, sugar alcohols, colloidal silica, maltodextrin, starch, and mixtures thereof.