Form 2
The Patents Act 1970
(39 of 1970)
Complete Specifications
Section 10, rule 13
A PROCESS FOR THE PREPARATION OF A PHARMACEUTICAL COMPOSITION CONTAINING CYCLO OXYGENASE INHIBITOR SUBSTANCE FOR ORAL
ADMINISTARTION
Applicant : Unichem laboratories Ltd, an Indian company, having office Mahalaxmi Chambers , 2nd Floor,22,Bhulabhai Desai Road, Mumbai 400026, India
The following specification particularly describes the nature of this invention and the manner in which it is to be performed :-


16 AUG 2OO4

Back ground of invention :
The present invention relates to the process of preparation of suspension composition for oral use of a pharmaceutical active substance such as cyclooxygenase (COX) inhibitor and a process for preparing the same. The ability of COX inhibitors to selectively block formation of pro-inflammatory prostaglandins while sparing those that guard the gastro- intestinal tract makes them an attractive choice for long term use and therefore various pharmaceutical forms viz. tablets, capsules, sacnets, injections etc. are available for administration ot COX-2 inhibitors such as meloxicam. Several patents and bibliographic references disclose different types of dosage forms containing Cox- 2 inhibitors such as meloxicam. US 6264269, US 20020187187, EP 2002256741, EP1250921, WO 03057136, WO 02098352, WO 02067894, US 20030068373, US 6479551, CN 1322523 disclose fast disintegrating tablet compositions of meloxicam. Also, WO0048583, WO03070251 and US200209904 disclose tablet compositions containing meloxicam in combination with 5- HT agonist, codeine and oxycodone respectively. IT 1251650 discloses tablet composition of meloxicam complexed with betacyclodextrin. DE 10161077, WO 03086469 and EA 2497 disclose injectable compositions of meloxtcam. CA 2332271 discloses aqueous composition of meloxicam for ophthalmic use. EP 1348436, WO 03059318 and WO 03035080 disclose suppository, tampon and topical formulations of meloxicam. The systemic formulations viz. tablets have to be administered to animals using a feeding gun, the process being extremely cumbersome. In case of fast disintegrating tablets viz. mouth dissolve tablets [WO 02067894] or chewable tablets [US 20030175336] these products are unsuitable for veterinary use.
The injectable formulations need specialized medical personnel for administration and also poses discomfort to the animals during administration. Hence, the best possible formulation which could be administered to both animals as well as mankind is a liquid oral composition, that is of stable quality, simple to manufacture and easy to administer.

Solutions and syrups essentially have the advantage that they can be accurately measure out and easy to administer for veterinary use as well as human use. For safe administration of meloxicam and other active substances e.g. other NSAIDs , a liquid oral preparation is desirable as an alternative to the solid form (capsule, tablets) particular in paediatrics and in veterinary use. Patents US 6184220 and EP 0945134 disclose liquid oral composition of meloxicam. These suspensions of meloxicam are stabilized using finely divided silica powder viz. Aerosil in a hydrophilic polymer matrix medium and is manufactured under high shear stirring to result in a 3 dimensional silioid structure. The stability of the composition is based on the delicate 3- dimensional silioid structure and any slight change in this structure results in heavy sedimentation of the drug leading to variations in amount of drug administered. Moreover, handling finely divided silica powder itself is extremely hazardous, the situation becomes more complex since the manufacturing of the composition is done under high shear as disclosed in the patent. Also the process proposed in the patent advises use of vacuum during entire suspension manufacturing thereby increasing energy consumption and posing safety hazard in production area. Also, the process listed in prior art e.g. US 6184220 recommends grinding of the active pharmaceutical moiety prior to usage in the suspension product, thereby increasing production cycle times and product cost.
Some of the processes listed in prior art e.g. WO 02098352 employ use of large quantities of buffering agents there by increasing ion- content of the product, thereby increasing ion content when administered to the mammal. There is therefore need to formulate pharmaceutical composition of the COX- inhibitor that would be easy to produce on the industrial scale for commercialization and give a product with desired stability , quality and accuracy of dosing.

There is also a need to develop a safe product i.e. without undue dosing of ionic salts inside the product.
Scope of the invention:-
The objective of the present invention is to develop a process to obtain pharmaceutical suspension composition for oral use containing a COX-inhibitor or a pharmaceutically acceptable salt or derivative or prodrug thereof.
The further objective of the present invention is to develop a process to obtain pharmaceutical suspension composition of COX-inhibitor or a pharmaceutically acceptable salt or derivative or prodrug thereof., which is safe and efficacious.
The further objective of the present invention is to develop a process to obtain pharmaceutical composition of a COX-inhibitor or a pharmaceutically acceptable salt or derivative or prodrug thereof as a drug delivery system that is accurate in dosing .
The further objection of the present invention is to develop a process to obtain pharmaceutical composition containing COX-inhibitor or a pharmaceutically acceptable salt or derivative or prodrug thereof which is stable and of acceptable quality.
The further objective of the present invention is to develop a process to obtain pharmaceutical composition containing COX-inhibitor or a pharmaceutically acceptable salt or derivative or prodrug thereof by employing a process that can be easy to manufacture at an industrial scale, employing standard machines.

The following pharmacologically active substances are mentioned as examples of COX -inhibitors valdecoxib, meloxicam, rofecoxib, etoricoxib,parecoxib, lumiricoxib although this list should not be regarded as limiting this category of active substances.
Most preferably the suspension composition of the present invention is free of hydroxy ethyl or propyl cellulose, hydroxy propyl methyl cellulose, buffer salts, aerosil, glycerine, xylitol, sodium borate, citric acid and its salts, sorbitol and may not be manufactured using vacuum.
Detailed description of the invention :
The present invention provides a process to obtain pharmaceutical composition useful for and a method for treating pain related disorders, in particular muscular or skeletal pain disorders such as muscle pain , arthritis, osteoarthritis, inflammation, acute and chronic pain, chemo prevention, dental pain, gout, rheumatoid arthritis and the like disorders. The pharmaceutical composition produced by the present processprovides relief of pain symptoms when administered to a mammal.
In one embodiment, the COX - inhibitor formulation produced by the present process is available for absorption as an immediate release dosage form.
In another embodiment, the COX inhibitor formulation produced by the present process is released sequentially over time from 1- 24 hours as timed or pulsed or sustained or delayed release.
Cox- inhibitor compounds disclosed in the present invention may be used in their native forms or as salts. In cases, where forming a stable non-toxic acid or base salt is desired,

administration of the compound as a pharmaceutically acceptable salt may be appropriate. The phrase " pharmaceutically acceptable " is employed herein to refer to those compounds, materials, compositions and / or dosage form which are within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings or animals without excessive toxicity, irritation, allergic response or other problem or complication, commensurate with a reasonable benefit/ risk ratio.
Examples of pharmaceutically acceptable salts are organic acid addition salts formed with acid that form a physiological acceptable anion for example tosylate, methane, sulfonate, acetate citrate, malonate, tartarate, succinate, benezene sulfonate, benzoates, ascorbate, etoglutarate and glycerophosphate. Suitable in organic salts including hydrochloride, hydro bromide, sulfate, nitrate, bicarbonate and carbonate may also be formed insitu.
Pharmaceutically acceptable salts may be obtained using standard procedures well known in the art for example reacting a sufficiently basic compound such as an amine with a suitable acid affording a physiologically acceptable anion. Alkali metal (for example, sodium, potassium or lithium) or alkaline earth metal (for example calcium) salts of carboxylic acids can also be made.
The process disclosed in the present invention involves use of the COX - inhibitor substance or its derivative or salt or prodrug with preservatives, wetting agents, levigating agents, sweetners, flavors and other additives. The composition may or may not contain at least one further active ingredient.
The term 'prodrug' refers to a chemical compound that can be converted into a therapeutic compound by metabolic or simple chemical process within the body of the subject.

1
It will be appreciated by those skilled in the art that the compounds disclosed in the presen application may have a chiral center and be isolated in optically active and racemic forms Some compounds may exhibit polymorphism.
Cox-inhibitor drug substances present in the pharmaceutical composition disclosed in th< present invention encompass any racemic, optically active, polymorphic, tautomeric o stereoisomeric form or mixture thereof of the substance or its derivative or salt or prodruj that possesses the useful properties described therein. It is well known in the art how t< prepare optically active forms (for e.g. by resolution of the racemic forms througl recrystallization techniques by synthesis from optically active starting materials by chira synthesis or by chromatographic separation using a chiral stationery phase) and how to determine anti-inflammatory activity using standard tests or other tests that are well-known in the art.
The suspension composition prepared by the process of the present invention can be administered by oral route either as a ready liquid or a frozen candy, but preferably as a liquid dosage form.
The process of preparation of suspension disclosed in the present invention comprises of:
a. Preparation of sugar syrup containing preservatives such as methyl and prop)
parabens.
b. Soaking carbopol in water so as to form an effectively wetted mass.
c. Screening the active pharmaceutical substance or a pharmaceutically acceptable sa
or derivative or prodrug thereof through 30 # mesh. Add surfactant or wetting agei
such as Cremophore RH 40 and mix to produce a homogenous mass.

d. Adding the drug mass of step © to the syrup solution of step (a), followed by addition
of wetted carbopol mass from step (b) under constant stirring at optimum speed.
e. Add other pharmaceutical additives such as bulking agents, wetting agents, anti- foam
agents, surfactants, pH adjusters, flavors and stir to form a homogenous suspension.
COX - inhibitor substance or a pharmaceutically acceptable salt or a prodrug there of in pharmacologically effective concentration is added in a suspension base comprising of: 0 % to 60 % by weight of Microcrystalline cellulose (Avicel RC 591) preferably; 0 % to 10 % 0.1 % - 10 % by weight of Carbopol (Carbopol 971P); preferably 0.5 - 1.0 % by weight 0.1 % - 0.3 % by weight of Methyl paraben ; preferably 0.15-0.25 % by weight 0.01 % to 0.03 % by weight of Propyl paraben; preferably 0.015 - 0.025 % by weight 5 % to 67 % by weight of Sucrose; preferably 5-30 % by weight 0 % - 3 % by weight of Sorbic acid; preferably 0.1 - 2.0 % by weight 0 % to 5 % by weight of Simethicone; preferably0.5 % by weight
0 % - 5 % by volume of Flavoring agent such as pineapple, orange, anise, cardamom and the like followed by addition of levigating agent or vehicle; preferably water quantity sufficient to make 100 % by volume.
To get a smooth composition, the suspension composition of the present invention may then be preferably further passed through a colloid mill and later screened through a wire mesh of 30 # using well-known processes to those skilled in the art.
The preferred active component of the pharmaceutical composition of the invention is a COX inhibitor substance such as valdecoxib, meloxicam, etoricoxib, parecoxib, lumiricoxib or a pharmaceutically acceptable salt or a derivative or prodrug thereof although this list should not be regarded as limiting this category of active substances.

i ne cox-2 inhibiitor substance or its derivative or salt or prodrug may be added as 0.1- 97 % w/v of the suspension composition.
The composition prepared by the process of the present invention may also contain formulation additives viz. pH adjusters (acidifying agent / alkalinizing agents), anti-oxidants, colorants, flavorant, sweetening agents, flavor enhancers, preservatives, thickeners or viscosity enhancers and combinations thereof in levigating agents or vehicle.
As used herein, the term "Bulking agent" is intended to mean an inert substance used as a filler to create the desired bulk characteristics to the formulation. By way of example and without limitation microcrystalline cellulose, poly-saccharides, phosphates, dextrins, substituted and un-substituted cyclodextrins may be used in the composition disclosed in the present invention , but preferably microcrystalline cellulose may be used.
Examples of levigating agent or vehicle and without limitation include water, pharmaceutical grade edible oils such as corn oil, cotton seed oil, peanut oil, arachis oil and the like, triglycerides, isopropyl myristate, mineral oil, water-isopropanol mixture, water-ethyl alcohol mixture may be used, but preferably water may be used as vehicle base in the composition of the present invention.
The composition prepared by the process of the present invention can also include one or more commonly known surfactant and wetting agents that improve wetting and dispersion of the drug into the suspension. As used herein, the surfactant such as sodium lauryl sulfate, polysorbate 80, hydrogenated polyoxyl castor oil (Cremophore), poloxamer, hydrogenated castor waxes, sorbitan esters, glyceryl monoleate, docussate sodium and the like , without

limitation, may be incorporated into the formulation, but preferably Cremophore RH 40 may be used in the process of making the composition disclosed in the present invention.
As used herein, pH adjusters is intended to mean an agent which is used to provide the desired pH to the dosage form for product stability. Such compounds include, by way of examples and without limitation, hydrochloric acid, lactic acid, phosphoric acid, sulfuric acid, malic acid, tartaric acid, alginic acid and alginic acid salts, ammonia solution, sodium hydroxide solution, triethanol amine, triethyl amine may be used, but preferably hydrochloric acid or sodium hydroxide may be used in the process of making the suspension composition disclosed in the present invention. The amount of pH adjusters used the process of making the composition will be as desired to get the desired pH of the formulation.
As used herein, a preservative is an agent or combination of agents that inhibits or reduces or eliminates chemical degradation and / or microbial growth in a pharmaceutical dosage form. Examples of preservative.without limitation include parahydroxy benzoates and soluble salts thereof, butylated hydroxy anisole, butylated hydroxy toluene, ascorbic acid, tocopherol, edetic acid and its sodium, potassium and calcium salts, bronopol, sodium chloride, propyl gallate, sodium ascorbate, sorbic acid, sodium and potassium metabisulphite, ascorbyl pamlmitate, sodium bisulphate in effective concentration may be incorporated into the formulation, but preferably methyl and propyl para hydroxy benzoates and / or sorbic acid may be used in the process of making the suspension composition disclosed in the present invention.
As used herein, the term "anti-caking agents" is intended to mean an agent that promotes re-dispersion of the solid content in the suspension on shaking or tossing. Examples of such anti-caking agents and without limitation include talc, carbopol , microcrystalline cellulose

and the like may be added to the formulation, but preferably microcrystalline cellulose may be used in the process of making the suspension composition disclosed in the present invention. Anti- foaming agents such as dimethicone, simethicone, polypropylene glycol and the like may be used, but preferably simethicone may be used in effective concentration in the process of making the suspension composition disclosed in the present invention.
The composition prepared as per the process disclosed in the invention can also include one or more viscosity enhancers. As used herein, the term " viscosity enhancer" impart desired viscosity to the suspension in order to provide accuracy of dosage during administration and also to prevent sedimentation of solid mass on storage. Examples of viscosity enhancer and without limitation include carboxy methyl sodium / potassium, carragenan, chitosan, dextrins, substituted and un- substituted cyclo dextrins, gelatin, microcrystalline cellulose, povidone, poly vinyl alcohol, sodium alginate, xanthan gum, tragacanth, acacia, guar gum, starch, zinc stearate may be used in the process to prepare the formulation, but preferably carbopol in effective concentration may be used in the process of making the suspension composition disclosed in the present invention.
As used herein, the term " flavoranf is intended to mean a compound used to impart pleasant flavour and often to a pharmaceutical preparation. Exemplary flavoring agents or flavorant include synthetic flavor oils and flavoring aromatics and/ or natural oils, extracts from plants, leaves, flowers, fruits and so forth and combinations thereof. These may also include cinnamon oil, oil of winter green, peppermint oils, clove oils, bay oils, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg, bitter almonds and the like. Other useful flavors and without limitation cherry, butterscotch, mango, pineapple, orange, peppermint, mixed fruit, caramel, black-current, vanilla, spearmint etc., shall be added to the formulation. The amount of flavoring may depend on a number of factors including the

organoleptic effect desired. Flavors will be present in any amount as desired by those of ordinary skill in the art.
As used herein, the term "flavor enhancers" is intended to mean a compound added into a formulation in order to enhance the organoleptic property of the formulation in synergy with the effect of the flavorant. Examples of flavor enhancers and without limitation include aspartame, acesulfame potassium, mono sodium glutamate, tartaric acid, menthol, camphor, polacrin and polacrin potassium, sodium chloride, sucrose, invert sugar and the like may be added to the process of making the suspension composition, disclosed in the present invention but preferably sugar and pineapple flavor may be used.
As used herein, the term "colorant" is intended to mean a compound used to impart color to the pharmaceutical preparation. Such compounds include , by way of example and without limitation, soluble or lake colours of sunset yellow, caramel, quionoline yellow, tartrazine yellow, ponceau red, erythrosine pink, iron oxides etc., wherever necessary may be incorporated into the formulation. The amount of coloring agent used will vary as desired. The pharmaceutical composition containing COX-2 inhibitor or its derivative or salt or prodrug formed as a result of the presented process, has been evaluated in-vitro for its uniformity of dispersion, assay, dissolution in surrogate biological fluids, pH, viscosity and photo-sensivity to natural and UV light.
Studies for drug availability for absorption with respect to time using in the-vitro dissolution rate test, the suspension composition disclosed in the present invention showed superior drug solubility measured as amount of meloxicam dissolved in simulated gastric or simulated intestinal fluid versus time in comparison with commercially available suspension formulation as reference products.

Oral formulation embodiment according to the present invention containing Meloxicam especially exhibited increased drug availability than that observed with reference products. Also, the impurity profile of the present embodiment complies acceptance criteria when compared with plain drug .
The pharmaceutical composition so produced as disclosed in the present invention has been evaluated for stability at several combinations of temperature and relative as per standard stability test guidelines prescribed by ICH (International conference on harmonization) for a period between 1-36 months. The stability samples were analyzed by chromatographic techniques viz. HPLC for assay as well as impurities and were been found to be stable and the quantity of the medicament as well as impurities / related substances well within specified limits. The pharmaceutical composition so disclosed in the present invention is therefore stable, of acceptable quality, efficacious and safe for administration to mammals.
The pharmaceutical composition so produced as disclosed in the present invention can be re-dispersed easily on shaking or tossing. Moreover, each 5 ml of the re-dispersed suspension of the present invention when analyzed for drug content showed assay value between 95-105 % w/v of the label claim; the standard limits for the suspension being 80 -120 % w/v. The suspension composition as disclosed in the present invention is therefore accurate in dosing.
The process of manufacture of the pharmaceutical composition disclosed in the present invention could be made using standard machines and without the use of vacuum, Moreover, the active substance was screened only through 30 mesh as per routine GMP (good

manufacturing practices) screening instead of using jet/ hammer mills which use high electrical energy and time.
The process of manufacture of the for preparation of the pharmaceutical composition disclosed in the present invention was also tried out on commercial scale machines and was found to be easy, simple and feasible to implement on industrial scale.
The above specified specification can be better understood with the help of examples However, these examples do not in any way restrict the broad scope of the invention.
Example 1:
Each 5 ml of the suspension to contain Meloxicam (7.5 mg), Avicel (87.5 mg), carbopol (10 mg), cremophore (7.5 mg), methyl paraben(10.0 mg), propyl paraben(1.0 mg), sugar (1 g), pineapple flavor, concentrated hydrochloric acid (to adjust pH 3.5 - 5.5) and water (quantity sufficient to 5 ml).
The suspension is made as follows: methyl and propyl parabens are dissolved in hot water ( up to 100°C). Sugar syrup is prepared . The preservative solution is then added to the syrup (base A). Carbopol is soaked in sufficient water to form an effectively wetted mass. Meloxicam is screened through mesh 40 # and added under stirring to the syrup base (A). Then add cremophore and stir. The carbopol swelled mass is then added to this drug slurry under constant stirring, Add concentrated hydrochloric acid to adjust pH between 3.5 -5.5. Once the temperature of the suspension has reached to ambient room temperature, the flavor is added.

Example 2:
Each 5 ml of the suspension to contain Meloxicam (7.5 mg), Avicel (87.5 mg), carbopol (10 mg), cremophore (7.5 mg), methyl paraben(10.0 mg), propyl paraben(1.0 mg), sugar (1 g), sorbic acid (5mg), flavor, concentrated hydrochloric acid (to adjust pH 3.5 - 5.5) and water (quantity sufficient to 5 ml).
The suspension is made as follows : methyl and propyl parabens , sorbic acid are dissolved in hot water (up to 100°C). Sugar syrup is prepared . The preservative solution is then added to the syrup (base A). Carbopol is soaked in sufficient water to form an effectively wetted mass. Meloxicam is screened through mesh 40 # and added under stirring to the syrup base (A). Then add cremophore and stir. The carbopol swelled mass is then added to this drug slurry under constant stirring, Add concentrated hydrochloric acid to adjust pH between 3.5 -5.5. Once the temperature of the suspension has reached to ambient room temperature, the flavor is added.
Example 3 :
Each 5 ml of the suspension to contain Valdecoxib (10 mg ), Avicel (87.5 mg), carbopol (10 mg), cremophore (7.5 mg), methyl paraben(10.0 mg), propyl paraben(1.0 mg), sugar (1 g), pineapple flavor, simethicone(0.1 mg), concentrated hydrochloric acid (to adjust pH 3.5 -5.5) and water (quantity sufficient to 5 ml).
The suspension is made as follows : methyl and propyl parabens are dissolved in hot water ( up to 100°C). Sugar syrup is prepared . The preservative solution is then added to the syrup (base A). Carbopol is soaked in sufficient water to form an effectively wetted mass. Meloxicam is screened through mesh 40 # and added under stirring to the syrup base (A). Then add cremophore and simethicone and stir. The carbopol swelled mass is then added to


this drug slurry under constant Stirring, Add concentrated hydrochloric add to adjust pH between 3.5 -5.5. Once the temperature of the suspension has reached to ambient room temperature, the flavor is added.
Example 4:
Each 5 ml of the suspension to contain VaJdecoxib (20 mg), Avicel (87.5 mg), carbopol (10 mg), cremophore (7.5 mg), methyl paraben(10.0 mg), propyl paraben(1.0 mg), sorbic add (5mg) sugar (1 g), pineapple flavor, simethicone(0.1mg),concentrated hydrochloric add (to adjust pH 3.5 - 5.5) and water (quantity sufficient to 5 ml).
The suspension is made as follows : methyl and propyl parabens , sorbic add are dissolved in hot water (up to 100°C). Sugar syrup is prepared . The preservative solution is then added to the syrup (base A). Carbopol is soaked in sufficient water to form an effectively wetted mass. Meloxicam is screened through mesh 40 # and added under stirring to the syrup base (A). Then add cremophore and Simethicone and stir. The carbopol swelled mass is then added to this drug slurry under constant stirring, Add concentrated hydrochloric add to adjust pH between 3.5 -5.5. Once the temperature of the suspension has reached to ambient room temperature, the flavor is added.

We Claim,
1) A process for manufacture of a pharmaceutical composition containing Cox-2 inhibitor non - steroidal anti-inflammatory agent or a pharmacologically acceptable salt or pro-drug there of in pharmacologically effective concentration in a suspension base comprising of:
0.1 % to 60 % by weight of Microcrystalline cellulose (Avicel RC 591)
preferably ; 0.1 % to 10 %
0.1% - 10 % by weight of Carbopol (Carbopol 971P); preferably 0.5 -
1.0 % by weight
0.1% - 0.3 % by weight of Methyl paraben ; preferably 0.15 - 0.25 % by
weight
0.01 % to 0.03 % by weight of Propyl paraben; preferably 0.015 - 0.025
% by weight
5 % to 67 % by weight of Sucrose; preferably 5 - 30 % by weight
0.1 % - 3 % by weight of Sorbic acid; preferably 0.1 - 2.0 % by weight
0.1 % to 5 % by weight of Simethicone; preferably 0.5 to 1.0 % by weight
0.1 % - 5 % by volume of Flavoring agent such as pineapple, orange,
anise, cardamom followed by addition of levigating agent or vehicle;
preferably water quantity sufficient to make 100 % by volume, prepared
as follows:
a. Prepare sugar syrup and add preservatives such as methyl and propyl
parabens.
b. Soak carbopol in water.

c. Screen the active pharmaceutical substance or a pharmaceutically
acceptable salt or derivative or prodrug thereof through a sieve. Add
surfactant or wetting agent such as Cremophore RH 40 and mix to
produce a homogenous mass.
d. Adding the drug mass of step c, to the syrup solution of step (a), followed
by addition of wetted carbopol mass from step (b) under constant stirring
at optimum speed.
e. Add Avicel RC 591, Simethicone and adjust the pH of the suspension
using hydrochloric acid or sodium hydroxide solution to range pH between
3.5 - 6.5; preferably 4.5- 5.5. Then add pine apple or orange or anise or
cardamoom flavor and stir to form a homogenous suspension. Make up
the volume of the suspension to 100 % using vehicle such as water.
2) A process as claimed in Claim 1 to make a stable pharmaceutical composition wherein the non-steroidal anti-inflammatory agent or a pharmaceutically acceptable salt thereof is for example meloxicam or valdecoxib, or parecoxib or etoricoxib or lumirocoxib alone or in combinations thereof.
3) A process as described) in Claims 1- 2 to provide a pharmaceutical composition comprising of a non-steroidal anti-inflammatory agent or its pharmaceutically acceptable salt incorporated with physiologically

accepted excipients selected in nature and quantities to prepare a liquid oral composition or powder for reconstitution .
4) A process as claimed in Claims 1-3, where in the amount of non-steroidal anti-inflammatory agent or a pharmaceutically acceptable salt thereof in the pharmaceutical compositions is in the range of about 0.1 % to 95% by weight of drug or its pharmaceutical^ acceptable salt.
5) A process as claimed in Claims 1-4, wherein the physiologically acceptable excipients such as microcrystalline cellulose used is at 0.1 % to 60 % by weight but preferably at 0.1 to 10 % by weight.
6) A process as claimed in Claims 1-5, wherein the physiological acceptable excipients such as carbopol used is at 0.1% to 10 % by weight but preferably at 0.5 to 1. 0 % by weight.
7) A process as claimed in Claims 1-6, wherein the physiologically acceptable excipients such as methyl paraben used is at 0.1 % to 0.3 % by weight but preferably at 0.15 % to 0.25 % by weight.
8) A process as claimed in Claims 1-7, wherein the physiologically acceptable excipients such as propyl paraben used is at 0.01 % to 0.03 % by weight but preferably at 0.015 % to 0.025 % by weight.

9) A process as claimed in Claims 1-8, wherein the physiologically
acceptable excipients such as sucrose used is at 5 % to 67.0 % by weight
but preferably at 5 % to 30 % by weight.
10) A process as claimed in Claims 1-9, wherein the physiologically acceptable excipients such as sorbic acid used is at 0.1 % to 3.0 % by weight but preferably at 0.1 % to 2.0 % by weight.
11) A process as claimed in Claims 1-10, wherein the physiologically acceptable excipients such as simethicone used is at 0.1 % to 5.0 % by weight but preferably at 0.5 % to 1.0 % by weight.
12) A process as claimed in Claims 1-11, wherein the physiologically
acceptable excipients such as flavoring agent used is pineapple or anise
or orange or cardamom.
13)A process as claimed in Claims 1-12, wherein the non-steroid anti¬inflammatory agent is Valdecoxib or a pharmaceutically acceptable salt thereof.
14)A process as claimed in Claims 1-13, wherein the non-steroidal anti¬inflammatory agent is Parecoxib or a pharmaceutically acceptable salt thereof.

15) A process as claimed in Claims 1-14, wherein the non-steroid anti-inflammatory agent is Etoricoxib or a pharmaceutically acceptable salt thereof.
16) A process as claimed in Claims 1-15, wherein the non-steroid anti¬inflammatory agent is Lumirocoxib or a pharmaceutical ly acceptable salt thereof
17)A process as claimed In Claims 1-16, wherein the non-steroid anti¬inflammatory agent is Meloxicam or a pharmaceutically acceptable salt thereof.
18) A process for preparation of a pharmaceutical composition for oral use containing a non-steroidal anti-inflammatory agent or a pharmaceutically acceptable salt thereof or prodrug thereof as claimed in Claims 1-17, substantially as described herein before with reference to Examples 1 -4.


Dated this 9th day of March 2004