Title of Invention

PROCESS FOR THE MANUFACTURE OF MEDICATED STICK FOR TOPICAL APPLICATION

Abstract

A method/process for the manufacture of a pharmaceutical composition for topical administration in the form of a medicated stick which comprises an active ingredient; 10 to 90% by weight of solvent comprising one or more polyhydric alcohols; 0.5 to 5% by weight of dibenzylidene sorbitol; 0.5 to 1% by weight of a thickenging agent comprising one or more chemically modified celluloses, polyacrylic acid copolymers; 0 to 60% by weight of a monohydric C1-6 alcohol; and 0 to 20% by weight of water provided that the total amount of solvent and water togther comprise at least 85% by weight of the composition.

Full Text

FORM 2 THE PATENTS ACT, 1970 (39 of 1970) COMPLETE SPECIFICATION (See Section 10) PROCESS FOR THE MANUFACTURE OF MEDICATED STICK FOR TOPICAL APPLICATION M/S. CIPLA LIMITED, MUMBAI CENTRAL, MUMBAI-400 008, MAHARASHTRA, India, an Indian Company incorporated under the Companies Act, 1956. The following specification particularly describes and ascertains the nature of this invention, and the manner in which it is to be performed. GRANTED 26-7-2007 The present invention relates to the method/process for the manufacture of medicated sticks for topical application to human skin. The composition can contain either of the following bulk drugs as the active ingredient:- Didofenac or a salt thereof (particularly sodium) / Acyclovir or a salt thereof (particularly sodium), Mometasone or a salt thereof, Beclomethasoneora salt of thereof (particularly dipropionate) /Fluticasone or a salt thereof (particularly propionate), Betamethasone or a salt thereof (particularly dipropionate), menthol methyl salicytate and/or cyclosporin. In the manufacture of medicated sticks , problems have arisen when it has been necessary to store these sticks prior to sale or use. In particular, shrinkage due to loss of volatile ingredients often occurred resulting in the sticks becoming mishappened and brittle as they dry out. In the case where medicated sticks were prepared as transparent sticks, a further problem was that these sticks often became opaque with storage and consequently tansparent sticks have generally been commercially unavailable. It has been proposed in US Patent, inventor Ronald Smith, to use alkoxylated compounds in sodium stearate stick compositions which were alkaline in nature having a pH from 7.5 to 9.5. These stick compositions did not tend to exhibit desirable transparency and often became cloudy or hazy on storage. Furthermore, the compositions were generally unstable and became mishappened and showed browning on storage. It has also been proposed in Japanese Patent Kokai No.49/85250 of Tombo Pencil Co., to provide solid perfumery products in the form of a stick containing a sorbitol/benzaldehyde condensation product, ethanol water and propylene glycol, in addition to a substantial amount of perfume. This Japanese patent also described replacement of propylene glycol with glycerol together with hydroxypropylcellulose which is incorporated as a hardener. These products proposed by the Tombo Pencil Co., were however unsatisfactory, in that they showed a tendency to shrink and deform due to evaporative loss of ethanol. Furthermore, the presence of an excessively high level of ethanol could also provoke a stinging sensation when the stick was applied topically to human skin, and could lead to defatting and dehydration of the skin. These properties render the product unsatisfactory and unacceptable for normal use. US patent 4 518 582 (American Cyanamid Co) describes antiperspirant stick compositions containing dibenzylidene monosorbitol acetal in the presence of an acidic antiperspirant active salt, such as aluminium, chlorohydrex, together with 1,3-butytene glycol, anhydrous ethanol, hydroxypropyl cellulose and other! ingredients. Sticks such as these, however, lost their stability if water was present, because of hydrolysis of the dibenzylidene monosorbitol acetal in the presence of the acid antiperspirant salt. Such sticks containing antiperspirant actives can also be cosmetically unacceptable inthat they can become sticky following topical application, and they can be rejected by the consumer interfering with the body"s natural function of sweating in response to excessive heat or exercise. European Patent 0044, 543 describes the cutaneous route of administration of a number of acyclovir formulations suitable for skin ^ppJication as aqueous cream are in particular oil/water emulsions. However, these and other formulations such as for instance those described in WO 95/16434 and WO 94/05258 are inconvenient for application since dosage for treating herpes and in particular" herpes labialis with acyclovir includes several and frequent applications of the topical formulation, especially in the early stages of development of herpes. This causes patients to have the formulation constantly at hand throughout the day, atleast during the first few weeks of treatment. We have now found that the hitherto expereinced problems can be .alleviated by the use of specific amounts of ingredients suitable for use in compositions for topical administration and in particular medicated sticks. There is provided by the present invention method of preparing pharmaceutical composition of a medicated stick which comprises of an active ingredient; 10 to 90 % by weight of a solvent comprising one or more polyhydric alcohols; 0.5 to 5% by weight of dibenzylidene sorbitol; 0.5 to 1 % by weight of a thickening agent comprising one or more chemically modified cellulose"s, polyacrylic acids and polyacrylic acid copolymers ; 0 to60% by weight of a monohydrie alkanol, if used chosen from C1 to C6 monohydrie alkanols; and 0 to 20% by weight of water; provided that the total amount of solvent and water, if used comprise atleast 85% by weight of the composition. The active Ingredient typically comprises one or more of Diclofenac or a salt thereof (particularly sodium) / Acyclovir or a salt thereof (particularly sodium), Mometasone or a salt thereof, Beclomethasone or a salt thereof (partiGuJarly dipropionate) / Fluticasone or a salt thereof (particularly propionate), Betamethasone or a salt thereof (particularly dipropionate), menthol methyl salicytate and/or cyclosporin. More particularly, the active ingredient is typically selected from the group consisting of 0.5 to 3% by weight (particularly about 1 %) Diclofenac or a salt thereof (particularly sodium), 1 to 10 % by weight (particularly 5%) of Acycloviror a salt thereof (particularly sodium), 0.025 to 1% by weight (particularly 0.1%) Mometasone, or a salt thereof, 0.025 to 1% by weight (particularly about 0.025% ) Beclomethasone or a salt thereof (particularly dipropionate), 0.025 to 1 % by weight (particularly about 0.05%) Fluticasone (particularly propionate), or a salt thereof, 0.025 to 1 % by weight (particularly about 0.5% ) Betamethasone or a salt thereof (particularly dipropionate), 2 to 10 % by weight (particularly 5.91 %) menthol, 2 to 25 % by weight (particularly about 12.8 %) methyl salicytate and 0.25 to 3 % by weight cyclosporin. A composition according to the present invention is in the form of a medicated stick that can be applied to the affected area directly. Such a composition has good local action and on application gives a thin layer on the skin that is non -greasy. Compositions according to the invention in medicated stick form are extremely practical to use and are also very effective particularly when compared to conventional creams or fatty ointments. The ease of use of compositions according to the invention leads to a more frequent and correct application of the active ingredient to the area involved and, as a result, to a more effective treatment of the disease. Polyhydric alcohols are generally employed in compositions according to the present invention as a solvent for dibenzylidene sorbitol. The polyhydric alcohols can also enhance the stability of the compoisitions by avoiding as far as possible the problems of shrinkage, deformity and brittleness that can occur due to evaporative loss of volatile materials, such as monohydric alcohol, present in the compositions. Examples of suitable polyhydric alcohols include ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol (PEG) with medium molecular weight typically lower than 1000 (e.g. between PEG 200 and 600), propylene glycol, dipropylene glycol, butylene glycol, octyl dodecanol, and dipropyleneglycolmonomethyl ether. Preferred polyhydric alcohols include dipropylene glycol and polyethylene glycol, i.e., PEG 200 and mixtures thereof. The amount of polyhydric alcohol present in the compositions according to the invention is preferably in-the range of 30 to 90% by weight of the composition. A metod of preparing a composition according to the invention suitably comprises water in an amount, of 5 to 20% by weight of the composition. The inclusion of water in compositions according to the present invention is advantageous in increasing the hardness and improving the dissolution of thickening agents like hydroxypropyl cellulose also present in the compositions. Dibenzylidene Sorbitol present in compositions according to the invention can advantageously provide structural rigidity without impairing transparency of the medicated sticks. The amount of dibenzylidene sorbitol present in the medicated sticks according to the invention is preferably from about 1 to 2.5% by weight of the composition. Examples of chemically modified cellulose"s suitable for use as a thickening agent in compositions according to the invention include hydroxypropyl cellulose, hydroxyethylcellulose and methylcellulose. The preferred thickening agent is hydropropylcellulose (HPC-M). Monohydric alkanols present in the compositions according to the invention can further assist in dissolving dibenzylidene sorbitol present in the compositions. Examples of C1 to C6 monohydric alkanols are methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, 1-butanol, n-pentanol, isopentanol, t-pentanol, n-hexanol. The preferred monohydric alkanol is ethanol which is commonly available as Industrial Methylated Spirits. The amount of the monohydric alkanol when present in the medicated stick according to the invention is preferably from 10to 30% by weight of the stick. A method of preparing a composition according to the invention can also further comprise dissolution aids such as butyrolactone, propylene carbonate or pyrrolidone to aid the dissolution of the dibenzylidene sorbitol in the solvent, particularly when monohydric alkanols are absent or only a very low level of monohydric alkanols are present or when low level or when volatile monohydric alkanols (such as methanol or acetone-*) are employed. A method of preparing a composition according to the invention can also further comprise one or more emollient oils to enhance the appeal of the composition. Examples of suitable emollient oils include isopropyl myristate, n-butyl phthalate, polyethyleneglycol 400, oleyl alcohol, as well as synthetic oils such as PPG-14 butyl ether (such as Fluid AP), Neobic A-20, PPG-5-Ceteth-20 (such as Procetyl AWS), PPG-3 Myristyl ether (such as Witconol APM) as well as lanolin, its alcohol"s and its esters. A method of preparing a composition according to the invention can further comprise a humectant such as sorbitol or the like. A method of preparing a composition according to the invention can also further comprise a cooling agent, such as menthol, or derivatives thereof or the like. A method of preparing a composition according to the invention can also further comprise one or more permeation enhancers like diethylene glycol monoethylether (transcutol), oleic acid, sodium oleate, oleoyl macrogol-6 glycerides or PEG-8 glyceryl linoleate or the like. A method of preparing a composition according to the invention can also further comprise one or more preservatives like methyl paraben, propyl paraben or the like. A method of preparing a composition according to the invention can alsofurther comprise one or more antioxidants like sodium metabisulfite or the like, to assist the stability of an active ingredient present in the composition. The choice of optional ingredients and the quantities employed should be such that the transparency, if required, of thisstick is not impaired. According to the present invention, there is provided a process / method for preparing the medicated stick for topical application which process comprises of the following steps:- forming a solution of dibenzylidene sorbitol in a solvent comprising one or more polyhydric alcohols; forming a mixture by adding to the solution formed in step (a) an active ingredient, a thickening agent comprising one or more chemically modified celluloses, polyacrylic acids and polyacrylic acid copolymers, a monohydric C1-6 alcohol and water; wherein the resulting composition comprises 10 to 90% by weight of the solvent, 0.5 to 5% by weight of dibenzylidene sorbitol, 0.5 to 1 % by weight of the thickening agent, 0-to 60% by weight of the monohydric C1-6 alcohol and 0 to 20% by weight of water; provided that the total amount of solvent and water together comprise at least 85% by weight of the composition. Suitably the solution obtained by step (a) is formed at a temperature of 85 to 90°C with stirring and preferably the active ingredient is then added thereto a temperature in the range of 70 to 80°C, such as about 75°C. According to a particular aspect of the invention a solution of the active ingredient is formed prior to addition thereof to the solution formed in step (a). According to an alternative aspect of the invention,-however., the active ingredient can be directly added to the solution formed in step (a) without any prior solution of the active ingredient. According to the present invention, the mixture formed in step (b) is formed into a medicated stick, for example by cooling it and casting it into a mould. Suitably a process according to the present invention can further comprise adding to the solution formed in step (a) one or more of an emollient oil, a humectant, a cooling agent, a permeation enhancer, a preservative and an antioxidant substantially as herein before described. A medicated stick obtained according to the present invention can be packed in a suitable holder with a removable cap to protect the stick and prevent the loss of any volatile ingredient therefrom. The present invention will now be further illustrated by the following Examples, which do not limit the scope of the invention in any way. Examples : Example 1 This example describes the process for manufacture of a transparent medicated stick according to the invention containing diclofenac sodium as active ingredient. Dipropylene glycol, PEG 200, propylene glycol and propylene carbonate are mixed together. The liquid-is slimed sufficiently rapidly to guarantee the immediate and even distribution of dibenzylidene sorbitol as the latter is added. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Once a clear solution is obtained, temperature is lowered to 75°C, Diclofenac sodium is added and solution stirred until diclofenac sodium was dissolved. Hydropropyl cellulose-M is added and mixed to get uniform solution. Sodium metabisulfite is dissolved in water and added to the above. The mixture is finally poured into a mould and allowed to cool under ambient condition. The Diclofenac sodium stick so prepared has following composition: Formula % w/w Diclofenac sodium 1% Dibenzylidene sorbitol 2% Dipropylene glycol 45% PEG 200 26.4% Propylene glycol 10% Propylene carbonate 5% Hydroxy propyl cellulose (HPC-M) 0.5% Water 10% Sodium metabisulfite 0.1 % This composition and process for manufacture can also be used for other salts of Diclofenac sodium. Example 2 This example describes the process for manufacture of a medicated stick according to the invention containing acyclovir as active ingredient. Dipropylene glycol, PEG 200, propylene glycol, propylene carbonate are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate and even distribution of dibenzylidene sorbitol as it is added. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Once a clear dibenzylidene sorbitol solution is obtained, temperature is lowered to 75°C. Acyclovir is added under continuous stirring to get uniform dispersion and sodium oleate and HPC-M is ad,ded and mixed. Water is added and mixed. The mixture is finally poured into a mould and allowed to cool under ambient condition. The Acyclovir stick so prepared has following composition: Formula % w/w Acyclovir 5% Dipropylene glycol 44% Propylene carbonate 5% PEG 200 15% Dibenzylidene sorbitol (DBS) 2% Propylene glycol 10% HPC-M 2% Water 16% Sodium oleate 1% This composition and process for manufacture of a medicated stick can also be used for Acyclovir sodium or other salts of Acyclovir. Example 3 This example describes the process for manufacture of a medicated stick according to the invention containing Betamethasone dipropionate. Dipropylene glycol, PEG 300 are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate even .distribution of dibenzylidene sorbitol as it is added. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Propylene glycol in a separate vessel is heated to 75°C and then Betamethasone dipropionate dissolved in it. Once a clear dibenzylidene sorbitol solution is obtained, temperature is lowered to 75°C. Then Betamethasone dipropionate solution is added under continuous stirring. Then HPC-M is added and mixed. The mixture is finally poured into a mould and allowed to cool under ambient condition. This Betamethasone dipropionate stick so prepared has the following composition:- Formula % w/w Dibenzylidene sorbitol 2% HPC-M 1% Dipropylene glycol 48.5% PEG 300 20% Propylene glycol 28% Betamethasone dipropionate 0.5% This composition and process for manufacture of a medicated stick can also be used for other salts pf Betamethasone propionate. Example 4 This example describes the process for manufacture of a medicated stick according to the invention containing Fluticasone propionate as active ingredient. Dipropylene glycol, PEG 300 are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate even distribution of dibenzylidene sorbitol as it is added. The vessel is heated to 85°G to 90°G to dissolve dibenzylidene sorbitol. Propylene glycol in a separate vessel is heated to 75°C and Fluticasone propionate dissolved in it, Once a clear dibenzylidene sorbitol solution is obtained, temperature is lowered to 75°C. Fluticasone propionate solution is added under continuous stirring. Then HPC-M is added and mixed. The mixture is finally poured into a mould and allowed to cool under ambient condition. The Fluticasone propionate stick so prepared-has the following composition:- Formula % w/w Dibenzylidene sorbitol 2% HPC-M 1% Dipropylene glycol 48.95% PEG 300 20% Propylene glycol 28% Fluticasone propionate 0.05% This composition and process for manufacture can also be used for other salts of Fluticasone propionate. Example 5 This example describes the process for manufacture of a medicated stick according to the invention Mometasone as active ingredient. Dipropylene glycol, PEG 300 are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate even distribution of dibenzylidene sorbitol as it is added. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Propylene glycol in a separate vessel is heated to 75°C and Mometasone is dissolved in it. Once a clear dibenzylidene sorbitol solution is obtained, temperature is lowered to 75°C. Mometasone solution is added under continuous stirring. Then HPC-M is added and mixed. The mixture is finally poured into a mould and allowed to cool under ambient condition. The Mometasone stick so prepared-has the following composition:- Formula % w/w Dibenzylidene sorbitol 2% HPC-M 1% Dipropylene glycol 48.9% PEG 300 20% Propylene glycol 28% Mometasone 0.1 % Example 6 This example describes the process for manufacture of a medicated stick according to the invention Beclomethasone dipropionate as active ingredient. Dipropylene glycol, PEG 300 are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate even distribution of dibenzylidene sorbitol as it is added. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Propylene glycol in a separate vessel is heated to 75°C and Beclomethasone dipropionate-dissolved in it. Once a clear dibenzylidene sorbitol solution is obtained, temperature is lowered to 75°C. -Beclomethasone dipropionate solution is added under continuous stirring. Then HPC-M is added and mixed. The mixture is finally poured into a mould and allowed to cool under ambient condition. The Beclomethasone dipropionate stick so prepared has the following composition:- Formula % w/w Dibenzylidene sorbitol 2% HPC-M 1% Dipropylene glycol 48.975% PEG 300 20% Propylene glycol 28% Beclomethasone dipropionate 0.025% This composition and the process for manufacture can also be used for the other salts of Beclomethasone propionate. Example 7 This example describes the process for manufacture of a medicated stick according to the invention Diclofenac sodium as active ingredient. Ethanol was also included in the stick. .Dipropylene glycol and PEG 300 are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate and even distribution of dibenzylidene sorbitol as it is added. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Once a clear solution is obtained, temperature is lowered to 75°C, Diclofenac sodium is added and solution stirred until drug goes into solution. Then HPC-M is added and mixed to get a uniform solution. Sodium metabisulfite is dissolved in water and added to the transparent liquid mixture and mixed. Ethanol is then addedand mixed. The mixture is finally poured into a mould and allowed to cool under ambient condition. The Diclofenac sodium stick so prepared has following composition: Formula % w/w Dibenzylidene sorbitol 2.5% HPC-M 0.8% Dipropylene glycol 60.6% PEG 300 15% Ethanol 10% Diclofenac sodium 1% Sodium metabisulfite 0.1% Water 10% This composition and process for manufacture can also be used for the other salts of Diclofenac sodium. Example 8 This example describes the process for manufacture of a medicated stick according to the invention combination of diclofenac sodium and methyl salicylate. Dipropylene glycol, PEG 200, propylene carbonate and propylene glycol are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate and even distribution of dibenzylidene sorbitol as it is added. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Once a clear dibenzylidene sorbitol solution is obtained, temperature is lowered to 75°C, Diclofenac sodium is added and solution stirred until drug goes into the solution. The HPC-M is added and mixed to get a uniform solution. Water is added and mixed. Then at temperature 65°C methyl salicylate is added and mixed to get transparent liquid mixture. The mixture is finally poured in a mould and allowed to cool under ambient condition. The Diclofenac sodium and methyl salicylate stick so prepared has the following composition. Formula % w/w Dibenzylidene sorbitol 2% HPC-M 0.5% Dipropylene glycol 38% PEG 200 23% Propylene carbonate 4% Propylene glycol 8.7% Water 10% Diclofenac sodium 1% Methyl salicylate 12.8% Example 9 This example describes the process for manufacture of a medicated stick according to the invention combination of methyl salicyate and menthol stick. Dipropylene glycol, PEG 200, propylene glycol, propylene carbonate are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate and even distribution of dibenzylidene sorbitol. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Once a clear solution is obtained, temperature lowered to 75°C. Then HPC-M is added and mixed to get a uniform solution and then water is added and mixed. Menthol is dissolved in methyl salicylate in a separate vessel. At 65°C temperature, menthol in methyl salicylate is added to the liquid mixture and mixed. The mixture is finally poured into a mould and allowed to cool under ambient condition. prepared has the following composition: - Formula % w/w Dipropylene glycol 35.33% PEG 200 21.67% Propylene glycol 7.86% Propylene carbonate 3.93% Water 10% HPC-M 0.5% Dibenzylidene sorbitol 2% Menthol 5.91% Methyl .salicylate 12.8% Example 10 This example describes the process for manufacture of menthol stick according to the invention. Dipropylene glycol, PEG 200 and propylene carbonate are mixed together. The liquid is stirred sufficiently rapidly to guarantee the immediate and even distribution of dibenzylidene sorbitol. The vessel is heated to 85°C to 90°C to dissolve dibenzylidene sorbitol. Once a clear solution is obtained, temperature is lowered to 750C. Then HPC-M is added and mixed to get a uniform solution and then water is added and mixed. Menthol is dissolved in propylene glycol in separate essel. At 650C temperature, menthol dissolved in propylene glycol is added to the liquid mixture and mixed. The liquid mixture is finally poured into a mould and allowed to cool under ambient condition. The stick so prepared has the following composition:- Formula %w/w Dibenzylidene sorbitol 2% HPC-M 0.5% Dipropylene glycol 44% Propylene carbonate 5% PEG 200 16.5% Propylene glycol 20% Water 10% Menthol 2% claim: 1. A pharmaceutical composition "for topical administration in the form of a medicated stick comprising, an active ingredient from 10% to 90% by weight, one or more polyhydric alcohols from 0.5 to 5% by weight and a dibenzylidene sorbitol 0.5% to 1% by weight,a thickening agent comprising one or more chemically modified celluloses, polyacrylic acids and polyacrylic acid copolymers 0.001% to 60% by weight, a monohydric CI-6 alcohol and 0.001% to 20% by weight of water provided that the total amount of solvent and water together comprise at least 85% by weight of the composition and-proeess of making thereof, 2. A Pharmaceutical composition as claimed in claim 1, wherein the active ingredient is selected from any of the following - diclofenac or a salt thereof, acyclovir or a salt thereof, mometasone or a salt thereof, betamethasone or a salt thereof, fluticasone or a salt thereof, menthol, methyl salicylate, cyclosporine, 3. A composition as claimed in claim 1, wherein the active ingredient is selected from any of the following - 1% diclofenac or a salt thereof, 1 to 10% acyclovir or a salt thereof, 0.1% mometasone or a salt thereof, 0.025% to 1% betamethasone or a salt thereof, 0.025% to 1% fluticasone or a salt thereof, 2 to 10% menthaol, methyl salicylate, 0.25 to 3% cyclosporine, 4. A composition as claimed in claim 1 and 2, wherein the active ingredient is selected consists essentially of diclofenac sodium and methyl salicylate, 5. A composition as claimed in above claims wherein the active ingredient consists essentially of diclofenac, 6. A composition as claimed in above claims wherein an active ingredient consists of methyl salicylate and menthol, 7. A composition as claimed in claim 1, wherein the solvent selected from the group of dipropylene glycol and / or polyethylene glycol, 8. A composition as claimed in above claims wherein the solvent used is selected in the range of 30% to 90% by weight of the composition,. 9. A composition as claimed in any of the above claims wherein the water is present in the range of 5% to 20% by weight of the composition, 10. A composition as claimed in claims 1 to 10 wherein the dibenzylidene sorbitol is [present in an amount of 1 to 25% by weight of the composition, 11. A composition as claimed in above claims wherein the thickening agent used in hydroypropylcellulose, 12. A composition as claimed in above claims wherein the monohydric alcohol is ethanol, in the range of 10% to 30% by weight of the composition, 13. A composition as claimed in claim 1, further comprising one or more of an emollient oil, a humactant, a cooling agent, a permeation enhancer, preservative and an antioxidant, 14. A process for preparing a pharmaceutical composition as claimed in above claims comprising the following steps, (a) forming a solution of dibenzylidene sorbitol consisting one or more polyhydric alcohols, (b) forming a mixture by adding to the solution formed in step (a) an active ingredient, a thickening agent comprising one or more chemically modified cellulose, polyacrylic acids and polyacrylic acids copolymers, a monohydric C1-6 alcohols and water, wherein the resulting composition comprises 10% to 90% by weight of the solvent,0.5% to 5% by weight of debenzylidene sorbitol, 0.5% to 1% by weight of the thickening agent, 0 to 60% by weight of the total amount of solvent and water together comprise at least 85% by weight of the composition, 15. A process as claimed in claim 14, wherein the solution of step (a) is formed at a temperature of 85% to 90%C, more particularly at 75C, 16. A process as claimed in claims 14 to 15 wherein a solution of the active ingredient is formed prior to addition thereof to the solution formed in step (a), 17. A process as claimed in claims 14 to 16 wherein the mixture formed in step (b) is cooled and cast into a mould to form a medicated stick, 18. A process as claimed in the above claims further adding to the solution formed in step (a) one or more of an emollient oil, a humectants, a cooling agents, permeation enhancer, a preservatives and an antioxidant, 19. A pharmaceutical composition for topical administration in the form of medicated stick such as herein described with reference to foregoing examples, 20. A process of preparing the pharmaceutical composition in the form of medicated stick, such as herein described with reference to an example, Dated this 2nd February, 1999. (V.RAMU) Agent for the Applicant

Documents:

180-bom-1999-cancelled page(26-07-2007).pdf

180-bom-1999-claim(granted)-(26-07-2007).doc

180-bom-1999-claim(granted)-(26-07-2007).pdf

180-bom-1999-correspondence(12-07-2007).pdf

180-bom-1999-correspondence(ipo)-(16-08-2007).pdf

180-bom-1999-form 18(29-12-2005).pdf

180-bom-1999-form 1a(16-03-1999).pdf

180-bom-1999-form 2(granted)-(26-07-2007).doc

180-bom-1999-form 2(granted)-(26-07-2007).pdf

180-bom-1999-other documkent(16-03-1999).pdf

180-bom-1999-power of attorney(16-03-1999).pdf