Form 2
The Patents Act 1970
(Act 39 of 70)
Complete Specifications
Section 10
A PHARMACEUTICAL COMPOSITION CONTAINING CYCLO OXYGENASE INHIBITOR
SUBSTANCE FOR ORAL ADMINISTRATION
Applicant : Unichem laboratories Ltd, an Indian company, having office at 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 :-

Back ground of invention :
The present invention relates to suspension composition for oral use of a pharmaceutical active substance such as cyclooxygenase (COX) inhibitor and a process for preparing the same.
Various pharmaceutical forms viz. tablets , capsules , sachets etc. are used for oral administration of drugs. Solutions and syrups essentially have the advantage that they can be administered with ease and also is easy to measure out for veterinary use.
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.
For safe administration of meloxicam and other active substances eg. Other NSAIDs , a liquid oral preparation is desirable as an alternative to the solid form (capsule, tablets) particular in paediatrics and in veterinary use.
The veterinary formulation should have smell and flavour which are suitable for numerous types of animals which can be treated with anti-rheumatic drugs, particularly various species of mammals to ensure that the course of treatment is completed and the therapy is guaranteed on the basis of good acceptance.
Several patents and bibliographic references disclose different types of dosage forms eg. Cox- 2 inhibitors such as meloxicam [ US 6284269, US 20020187187, IT 1251650, DE 10161077, EP 1348436, EP 2002256741, EP 125 0921, WO 03086469, WO 03059318, WO

03057136.WO 03035080, WO 02098352, WO 02067894.WO 03070251, US 20030068373, US 6479551, CN 1322523, US 20030175336, US 200209904, CA 2332271, WO 0048583, EA 2497, US 6184220 and EP 0945134 ].
Most of these patents refer to either tablet, capsule, injection, suppository, topical or ophthalmic compositions. Some of the per oral composition published so far can be prepared by process which are tedious and time consuming and present low yields of final product, thereby increasing production costs when produced on commercial scale.
Some of the processes listed in prior art 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.
Yet few other processes use large quantities of cellulose derivatives, silica compounds to stabilize the suspension from sedimentation and caking. Also these processes propose use of vacuum during entire suspension manufacturing thereby increasing electrical energy consumption and posing safety hazard in production area.
Also, some of the process listed in prior art recommend grinding of the active pharmaceutical moiety prior to usage in the suspension product, thereby increasing production cycle times, wastage of actice pharmaceutical substance during.the milling operation and consequently product cost.
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 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 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 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 objective of the present invention is to develop a 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 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. The particle size of the COX- inhibitor substance employed in this composition as disclosed in the present invention should be such that not less than 99 % is below 20 microns and not less than 90% is below 10 microns.
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, sorbitol, citric acid and its salts. The suspension composition of the present invention may not be manufactured using vacuum.
Detailed description of the invention :
The present invention provides a 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 provides relief of pain symptoms when administered to a mammal.
In one embodiment, the COX - inhibitor is available for absorption as an immediate release dosage form.
In another embodiment, the COX inhibitor may be 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 pharmaceuticaly 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.

It will be appreciated by those skilled in the art that the compounds disclosed in the present 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 the present invention encompass any racemic, optically active, polymorphic, tautomeric or stereoisomeric form or mixture thereof of the substance or its derivative or salt or prodrug that possesses the useful properties described therein. It is well known in the art how to prepare optically active forms (for e.g. by resolution of the racemic forms through recrystallization techniques by synthesis from optically active starting materials by chiral 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 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 preferred active component of the pharmaceutical composition of the invention is a COX inhibitor substance such as valdecoxib, meloxicam, rofecoxib, 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.
The cox-2 inhibitor substance or its derivative or salt or prodrug may be added as 0.1- 97 % w/v of the suspension composition.

The composition 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. The composition may comprise of at least one of such bulking agent. Alternatively, the composition may comprise of two or more of such bulking agent.
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 may comprise of at least one of such levigating agent Alternatively, the composition may comprise of two or more of such levigating agent.
The present dosage form can also include one or more commonly known surfactant or 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 composition disclosed in

the present invention. The composition may comprise of at least one of such surfactant or wetting agent. Alternatively, the composition may comprise of two or more of such surfactant or wetting agents.
As used herein, pH adjuster is intended to mean an agent which is used to provide the desired pH to the dosage form essentially to enhance 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 suspension composition disclosed in the present invention. The composition may comprise of at least one of such pH adjuster agent. Alternatively, the composition may comprise of two or more of such pH adjuster agent The amount of pH adjusters used in the formulation 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 preservatives and 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 palmitate, sodium bisulphate may be incorporated in effective concentration into the formulation, but preferably methyl and propyl para hydroxy benzoates and / or sorbic acid may be used in the suspension composition disclosed in the present invention. The composition may comprise of at least two of such preservatives. Alternatively, the composition may comprise of three or more of such preservatives.

As used herein, the term "anti-caking agent" 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 composition disclosed in the present invention. The composition may comprise of at least one of such anti- caking agent. Alternatively, the composition may comprise of two or more of such anti-caking agents.
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 suspension composition disclosed in the present invention. The composition disclosed in the invention can also include one or more anti-foam agents.
As used herein, the term " viscosity enhancer" impart desired viscosity to the suspension in order to prevent sedimentation of solid mass on storage. Quicker and effective re-dispersion on shaking and tossing thereby providing accuracy of dosage during administration. 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 disclosed formulation, but preferably carbopol in effective concentration may be used in the suspension composition disclosed in the present invention. The composition may comprise of at least one of such viscosity enhancing agent. Alternatively, the composition may comprise of two or more of such viscosity enhancing agents.

As used herein, the term " flavorant" 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 include cherry, butterscotch, mango, pineapple, orange, peppermint, mixed fruit, caramel, black-current, vanilla, spearmint and the like may be added to the formulation. The composition may comprise of at least one flavoring agent. Alternatively, the composition may comprise of two or more flavoring agent. 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 disclosed suspension in the present invention but preferably sugar and pineapple flavor or anise or cardamom flavor may be used. The composition may comprise of at least one of such flavor enhancing agent. Alternatively, the composition may comprise of two or more of such flavor enhancing agents.
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 wherever necessary may be incorporated into the formulation. The composition may comprise of at least one of such coloring agent. Alternatively, the composition may comprise of two or more of such coloring agents. The amount of coloring agent used wilt vary as desired.
The suspension composition disclosed in the present invention comprises of:
COX - inhibitor substance or a pharmaceutically acceptable salt or a prodrug 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 %to10 %
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 % by weight
0.1 % - 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 and is prepared as follows :
a. Prepare sugar syrup containing preservatives such as methyl and propyl parabens.
b. Soak carbopol in water so as to form an effectively wetted mass.
c. Screen the active pharmaceutical substance or a pharmaceutically acceptable salt or
derivative or prodrug thereof through 30 # mesh. 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 other pharmaceutical additives such as Avicel RC 591, Simethicone and adjust the pH of the suspension using commonly used pH adjuster such as hydrochloric acid or sodium hydroxide solution to range pH between 3.5 - 6.5; preferably 4.0- 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 or a like levigating agent.
Each 5 ml of the suspension composition of the present invention containing the COX inhibitor may contain COX inhibitor substance such as Meloxicam 7.5 mg or 15 mg. Each 5 ml of the suspension composition of the present invention containing the COX inhibitor may contain COX inhibitor substance such as Valdecoxib 10 mg or 20 mg or 40 mg . The particle size of the COX- inhibitor substance employed in this composition as disclosed in the present invention should be such that not less than 99 % is below 20 microns and not less than 90% is below 10 microns. To get a smooth product, the suspension composition of the present invention may then be optionally further passed through a colloid mill and later screened through a wire mesh of 30 mesh.
The composition of the present invention may optionally further comprise of an analgesic or and or an anti-pyretic.
The suspension composition disclosed in the present invention is recommended for administration to animals and mammals.
The pharmaceutical composition containing COX-2 inhibitor or its derivative or salt or prodrug has been evaluated in-vitro for its uniformity of dispersion, assay, dissolution in surrogate biological fluids, pH, viscosity and photo-sensitivity to natural and UV light.

Composition so prepared for oral use according to the present invention containing Meloxicam exhibited more than 85 % drug release in vitro dissolution study thereby promising bioavailability in vivo when administered to mammals.
The pharmaceutical composition so developed 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 for meloxicam 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 developed 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 meloxicam content showed assay value between 95- 105 % w/v of the label claim; the compendial limits for any 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 containing meloxicam 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 containing meloxicam was also tried out on commercial scale machines and was found to be easy, simple and feasible to implement on industrial scale.
Further, composition so prepared for oral use according to the present invention containing Vaidecoxib exhibited more than 85 % drug release in vitro dissolution study thereby promising bioavailability in vivo when administered to mammals.
The pharmaceutical composition so developed 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 for vaidecoxib 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 developed 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 vaidecoxib content showed assay value between 95- 105 % w/v of the label claim; the compendial limits for any 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 containing valdecoxib could be made using easily available machines and without the use of vacuum.
The process of manufacture of the for preparation of the pharmaceutical composition disclosed in the present invention containing valdecoxib 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, 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 4:
Each 5 ml of the suspension to contain Valdecoxib (20 mg), Avicel (87.5 mg), carbopol (10 mg), cremophore (7.5 mg), methyl paraben(10.0 mg), propyl paraben(1.0 mg), sorbic acid( 5mg) 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 , 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.

We Claim,
1) A pharmaceutical composition containing cyclooxegenase inhibitor
substance 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; 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 and
prepared as follows:
a. Prepare sugar syrup containing 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. Add 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 4.1 - 5.5. Then add pineapple or orange or anise or cardamom flavor and stir to form a homogenous suspension. Make up the volume of the suspension to 100 % using vehicle such as water or a like levigating agent.
2) A composition as claimed in Claim 1 wherein the cyclooxegenase inhibitor substance 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 composition as described in Claims 1- 2 to provide a pharmaceutical suspension comprising of a cyclooxegenase inhibitor substance or its pharmaceutically acceptable salt incorporated with physiologically accepted excipients selected in nature and quantities to formulate a liquid oral as powder for reconstitution.
4) A composition as claimed in Claims 1-3, where in the amount of cyclooxegenase inhibitor substance or a pharmaceutically acceptable salt thereof used in the pharmaceutical suspension, is in the range of about 0.1 % to 97 % by weight of drug or its pharmaceutically acceptable salt.
5) A composition 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 composition as claimed in Claims 1-5, wherein the physiologically 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 composition 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 composition 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 composition 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 composition 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 composition 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 composition as claimed in Claims 1-11, wherein the physiologically
acceptable excipients such as flavoring agent is pineapple or anise or
orange or cardamom used at 0.1 % to 5 % by volume but preferably at 2 %
to 4 % by volume.
13)A composition as claimed in Claims 1-12, wherein the cyclooxegenase inhibitor substance is Valdecoxib or a pharmaceutically acceptable salt thereof.

14)A composition as claimed in Claims 1-12, wherein the cyclooxegenase inhibitor substance is Parecoxib or a pharmaceutically acceptable salt thereof.
15) A composition as claimed in Claims 1-12, wherein the cyclooxegenase inhibitor substance is Etoricoxib or a pharmaceutical ly acceptable salt thereof.
16) A composition as claimed in Claims 1-12, wherein the cyclooxegenase inhibitor substance is Lumirocoxib or a pharmaceutically acceptable salt thereof.
17) A composition as claimed in Claims 1-12, wherein the cyclooxegenase inhibitor substance is Meloxicam or a pharmaceutical ly acceptable salt thereof.
18) A composition as claimed in Claims 1-17, wherein the particle size of the cyclooxegenase inhibitor substance is 99 % not less than 20 microns and 90 % not less than 10 microns.
19)A composition as claimed in Claims 1-18, that does not contain hydroxy propyl methyl cellulose or hydroxy propyl cellulose or hydroxy ethyl cellulose or sorbitol or mannitol or xylitol or buffer salts.
20)A composition as claimed in Claims 1-19, wherein the pH of the pharmaceutical suspension ranges between 4.1- 6.5, but preferably between 4.1-5.5.
21)A composition as claimed in Claims 1-20 further comprising of a flavouring agent, menthol, a sweetner, a preservative or a mixture of such.

22) A composition of a pharmaceutical composition for oral use containing cyclooxygenase inhibitor substance or a pharmaceutically acceptable salt or pro-drug thereof as claimed in Claims 1-21, substantially as described herein before with reference to Examples 1 -4.
Dated this 11th day of August 2004.