Title of Invention	A NOVEL COMPOSITION OF NON-AQUEOUS TOPICAL SOLUTION
Abstract	This invention relates to a novel topical liquid formulation comprising one or more active pharmaceutical ingredients selected from the group consisting of antiinflammatory drugs, anti-coagulants and local anesthetics. More particularly, the present invention relates to topical liquid formulation comprising diclofenac or its pharmaceutically acceptable salts employing effective combination of one or more pharmaceutically acceptable solvents, penetration enhancer and other pharmaceutically acceptable excipients.

Title of Invention

A NOVEL COMPOSITION OF NON-AQUEOUS TOPICAL SOLUTION

Abstract

This invention relates to a novel topical liquid formulation comprising one or more active pharmaceutical ingredients selected from the group consisting of antiinflammatory drugs, anti-coagulants and local anesthetics. More particularly, the present invention relates to topical liquid formulation comprising diclofenac or its pharmaceutically acceptable salts employing effective combination of one or more pharmaceutically acceptable solvents, penetration enhancer and other pharmaceutically acceptable excipients.

Full Text	FORM 2 THE PATENTS ACT 1970 (39 of 1970) & The Patents [Amendment] Rules, 2006 PROVISIONAL SPECIFICATION (See section 10 and rule 13) 1. TITLE OF THE INVENTION Non-Aqueous Topical Liquid Formulation 2. APPLICANT NAME : PATEL, Ketan R. NATIONALITY : IN ADDRESS : Troikaa Pharmaceuticals Ltd. 'Om Towers', Satellite Road, Ahmedabad - 380 015, Gujarat (IN) 3. PREAMBLE TO THE DESCRIPTION PROVISIONAL The following specification describes the invention. NON-AQUEOUS TOPICAL LIQUID FORMULATION Field of the Invention In general, this invention relates to a novel topical liquid formulation comprising one or more active pharmaceutical ingredients selected from the group consisting of antiinflammatory drugs, anti-coagulants and local anesthetics. More particularly, the present invention relates to topical liquid formulation comprising diclofenac or its pharmaceutically acceptable salts employing effective combination of one or more pharmaceutically acceptable solvents, penetration enhancer and other pharmaceutically acceptable excipients. Background of the Invention Diclofenac and its salts are known to have excellent anti-inflammatory analgesic effects and hence is one of the most popular drugs for pain management. Diclofenac salts are presented most commonly in the form of tablets, injectables, gels and recently as clear aqueous solution for topical use. When orally administered diclofenac preparations are known to produce GI side effects. Research and development work henceforth has been conducted on topical dosage forms of diclofenac with a view of providing localized action at site of pain. US Patent No. 4,652,557 describes pharmaceutical solutions containing active pharmaceutical ingredients including diclofenac in a solution comprising DMSO as penetration enhancer along with glycerol, propylene glycol and water. US Patent No. 5,093,133 describes the method for preparing hydro alcoholic gel of Ibuprofen for percutaneous delivery. The gel comprises ibuprofen along with alcohol, non-volatile solvent and gelling agents. US Patent Nos. 5,318,960 and 5,985,860 describes a composition for pain relieving NSAID's like ibuprofen, methotrexate, capsaicin, diphenhydramine, methylnicotinate, indomethacin, ketoprofen, aspirin, diclofenac sodium, etc and combinations thereof 2 produced for transdermal delivery. The compositions are manufactured by add mixing an appropriate amount of surfactant with an appropriate amount of co-solubilizers alcohol to establish a non-aqueous phase. There after an appropriate amount of distilled water is slowly added to form a clear oil continuous solution. US Patent No. 5,654,337 relates to a composition of pharmaceutically active substance including anti-inflammatory agent in a formulation, which is rapidly absorbed through the skin. The formulation comprises a polar lipid like lecithin, surfactant, water and urea with a pH of about 6-8. US Patent No. 6,054,484 describes transparent aqueous solution of diclofenac sodium dissolved in a mixed solvent of a fatty acid dialkylolamide and water. The aqueous solution claims to have higher penetration. US Patent No. 6,193,996 describes a pressure sensitive skin adhesive for transdermal delivery of diclofenac. The formulation incorporates effective amount of diclofenac or its pharmaceutically acceptable salts in the mixture of adhesives with penetration enhancer. W09857624 discloses an invention of pharmaceutical preparation for topical application containing alcohol along with short chain n-alkylpyrolidone and at least one pyrolidone substituted with long chain alkyl radical and water quantity sufficient. Diclofenac or its pharmaceutically acceptable salts and other NSAIDs produce their antiinflammatory analgesic action through inhibition of prostaglandin synthesis. On the other hand, counter irritants like menthol and methyl salicylate produce the sensation of heat at the site of application due to the increased blood circulation in the tissue. This mechanism of action helps alleviate pain and inflammation. Combination of diclofenac or its pharmaceutically acceptable salts with counter irritants have been formulated in the form of creams and gels to take advantage of various mechanisms of action of diclofenac and counter irritants. Combinations of diclofenac salts with counter irritants are available in the form of creams, gels and aerosols. 3 As it is apparent from the prior art that there have been a variety of approaches to enhance the penetration of diclofenac or its pharmaceutical acceptable salts as well as other NSAIDs. However, the preparation in all the prior arts incorporates water as one of the ingredients. One of the reasons for incorporating water in topical formulations such as creams and gels is to provide hydration, which is considered important for penetration of the active ingredients by hydrating the stratum corneum. More importantly water is used for its solubilizing property. Typical creams are prepared by dissolving water-soluble ingredients in the aqueous phase and the oil soluble ingredients in the oily phase. The two phases are mixed along with suitable surfactant to form a cream. Gels on the other hand only have aqueous phase and hence only water-soluble ingredients are incorporated. In case of aqueous solutions, water is used along with other co solvents and surfactants to solubilize the water-soluble ingredients of the formulation and also as a hydrating agent for the skin and in some cases water also helps reduce the viscosity of the solution. Furthermore, pharmaceutically acceptable salts of diclofenac are susceptible to oxidation. Since commonly used antioxidants like sodium metabisulphite, sodium sulphite, etc are water-soluble, water provides a suitable medium to incorporate the antioxidants in the aqueous solution of diclofenac. In case of creams and gels, due to the semisolid nature of the preparations, the amount of diclofenac that comes in contact with air is very much limited once the preparations are packed in suitable containers. However in case of aqueous solutions containing pharmaceutically acceptable salts of diclofenac, the movement of the topical solution within the container causes enough oxygen to dissolve in the solution and cause oxidative degradation of diclofenac salts resulting in yellow coloration. Although, water is an important ingredient for topical formulations of diclofenac salts for the aforementioned reasons, formulations comprising diclofenac and containing water will posses comparatively lesser stability than the non-aqueous diclofenac formulation. Therefore, there exists a need to formulate a stable, low viscous, non-aqueous, non-greasy topical solution comprising diclofenac or its pharmaceutically acceptable salts 4 diclofenac with an enhanced penetration of diclofenac into skin at the site of application of said topical solution. Description of the Invention It is an aspect of the present invention to provide a stable, low viscous, non-aqueous, non-greasy topical solution comprising diclofenac or its pharmaceutically acceptable salts, which exhibits enhanced transdermal absorption resulting in higher blood levels of diclofenac or its salts when compared to the formulations known in the art as creams, lotions, aqueous gels or aqueous solutions. In accordance with another aspect of the present invention, there is a topical solution comprising diclofenac or its pharmaceutically acceptable salts, wherein the solution comprises of diclofenac along with effective combination of propylene glycol, alcohol, penetration enhancers or other pharmaceutically acceptable excipients and optionally one or more humectants. In accordance with one other aspect of the present invention, there is a topical solution comprising diclofenac or its pharmaceutically acceptable salts, wherein said diclofenac is further used in the combination with other pharmaceutically acceptable active ingredients selected from anti-coagulants, anesthetics or counterirritants. Suitable anticoagulants herein used comprises of agatroban, cilostazol, citicoline, clopidogrel, cromafiban, dexanabinol, dicoumarol, dipyridamole, nicoumalone, oprevelkin, ozagrel, perindopril erbumine, phenindione, ramipril, repinotan, ticlopidine, tirofiban, and heparin, including heparin salts formed with organic or inorganic bases, and low molecular weight hssseparin, i.e., heparin fragments generally having a weight average molecular weight in the range of about 1000 to about 10,000 D and exemplified by enoxaparin, dalteparin, danaproid, gammaparin, nadroparin, ardeparin, tinzaparin, certoparin, and reviparin, but not limited to the above mentioned. 5 Suitable anesthetic herein used comprises of bupivacaine, chloroprocaine, oxyprocaine, mepivacaine, piperocaine, tetracaine, procaine, dibucaine, benzocaine, dyclaine and salts thereof, but not limited to the above mentioned. Suitable counterirritants herein used comprises of camphor oil, white, camphor powder synthetic technical, eucalyptol, eucalyptus oil, eucalyptus citriodora, menthol crystals, methyl cedryl ketone, methyl chavicol and methyl salicylate, but not limited to the above mentioned. Suitable pentration enhancers herein used comprises of sulphoxides (such as dimethylsulphoxide, DMSO), Azones (e.g. laurocapram), pyrrolidones (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes; Cyclodextrins, and cyclodextrin derivatives; but not limited to the above mentioned. Suitable humectants herein used comprises of include, but are not limited to the following materials acetamide MEA, aloe vera gel, arginine PCA, chitosan PCA, copper PCA, corn glycerides, dimethyl imidazolidinone, fructose, glucamine, glucose, glucose glutamate, glucuronic acid, glutamic acid, glycereth-7, glycereth-12, glycereth-20, glycereth-26, glycerin, honey, hydrogenated honey, hydrogenated starch hydrolysate, hydrolyzed corn starch, lactamide MEA, lactic Acid, lactose lysine PCA, mannitol, methyl gluceth-10, methyl gluceth-20, PCA, PEG-2 lactamide, PEG-10 propylene glycol, polyamino sugar condensate, potassium PCA, propylene glycol, propylene glycol citrate, saccharide hydrolysate, saccharide isomerate, sodium aspartate, sodium lactate, sodium PCA, sorbitol, TEA-lactate, TEA-PCA, urea, xylitol, and the like, as well as mixtures thereof, but not limited to the above mentioned Suitable solvents herein used comprises of ethers of polyethylene glycols, such as tetrahydrofurfuryl alcohol PEG ether (glycofurol, available commercially from BASF under the trade name Tetraglycol) or methoxy PEG (Union Carbide); amides, such as 2- 6 pyrrolidone, 2-piperidone, s-caprolactam, N-alkylpyrrolidone, N- hydroxyalkylpyrrolidone, N-alkylpiperidone, N-alkylcaprolactam, dimethylacetamide, and polyvinylpyrrolidone; dimethyl acetamide, dimethyl isosorbide (Arlasolve DMI (ICI)), N-methyl pyrrolidones (Pharmasolve (ISP)), monooctanoin, diethylene glycol monoethyl ether (available from Gattefosse under the trade name Transcutol), but not limited to the above mentioned. The present invention also provides the use of a device for applying said liquid formulation/composition to a desired area. The invention also provides for the massage of the desired area with the Roll on head of the device, after the application of liquid formulation/composition, without discharging additional liquid from the device, during the massage. Example 1 Composition of non-aqueous solution of Diclofenac or its pharmaceutically acceptable salts (Without Counter Irritants): S.No. Ingredients used Amount of the ingredient used 1 Diclofenac or its pharmaceutically acceptable salts 2.32% w/w10%w/w2% w/w 2 Ethanol 3 Oleic Acid 4 Propylene glycol Q.S Procedure: Ethanol and Oleic Acid are mixed and Diclofenac is dissolved in it. Then Propylene glycol is added Q.S and stirred well. 7 Example 2 Composition of non-aqueous solution of Diclofenac or its pharmaceutically acceptable salts (With Counter Irritants'): S.No. Ingredients used Amount of the ingredient used 1 Diclofenac or its pharmaceutically acceptable salts 2.32% w/w10% w/w 20% w/w 10% w/w 2 Ethanol 3 Methyl salicylate 4 Menthol 5 Propylene glycol Q.S Procedure: Diclofenac is dissolved in propylene glycol. Menthol and methyl salicylate are dissolved in Ethanol. The Ethanolic solution is then gradually added to the solution of Diclofenac in propylene glycol and the volume adjusted with Propylene glycol. Example 3 Composition of non-aqueous solution of Diclofenac or its pharmaceutically acceptable salts: S.No. Ingredients used Amount of the ingredient used 1 Diclofenac or its pharmaceutically acceptable salts 1.16% w/w15% w/w 20% w/w 10% w/w 2 Ethanol 3 Methyl salicylate 4 Menthol 5 Oleic Acid 2% w/w 8 6 Isopropyl myristate 1% w/w 7 Glycerol 1% w/w 8 Propylene glycol Q.S Procedure: Dissolve Diclofenac in Propylene glycol (around 10%). Dissolve Menthol in Methyl salicylate. Dissolve Glycerol in part of Ethanol (around 5%). Dissolve Isopropyl myristate in part of Ethanol (around 5%). Add 5% Ethanol to the solution of Methyl salicylate and Menthol. To this add the solution of Glycerol in Ethanol. To the resultant solution add the solution of Isopropyl myristate in Ethanol. Next add the solution of Diclofenac in Propylene glycol. Finally adjust the volume with Propylene glycol. While this provisional patent application contains the description of the principal inventive concepts. The complete patent application pursuant here to, will fully and particularly describe the preferred embodiments of the present invention.

Full Text

FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patents [Amendment] Rules, 2006
PROVISIONAL SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION
Non-Aqueous Topical Liquid Formulation
2. APPLICANT
NAME : PATEL, Ketan R.
NATIONALITY : IN
ADDRESS : Troikaa Pharmaceuticals Ltd. 'Om Towers', Satellite Road, Ahmedabad - 380 015, Gujarat (IN)
3. PREAMBLE TO THE DESCRIPTION
PROVISIONAL
The following specification describes the invention.

NON-AQUEOUS TOPICAL LIQUID FORMULATION
Field of the Invention
In general, this invention relates to a novel topical liquid formulation comprising one or more active pharmaceutical ingredients selected from the group consisting of antiinflammatory drugs, anti-coagulants and local anesthetics. More particularly, the present invention relates to topical liquid formulation comprising diclofenac or its pharmaceutically acceptable salts employing effective combination of one or more pharmaceutically acceptable solvents, penetration enhancer and other pharmaceutically acceptable excipients.
Background of the Invention
Diclofenac and its salts are known to have excellent anti-inflammatory analgesic effects and hence is one of the most popular drugs for pain management. Diclofenac salts are presented most commonly in the form of tablets, injectables, gels and recently as clear aqueous solution for topical use. When orally administered diclofenac preparations are known to produce GI side effects. Research and development work henceforth has been conducted on topical dosage forms of diclofenac with a view of providing localized action at site of pain.
US Patent No. 4,652,557 describes pharmaceutical solutions containing active pharmaceutical ingredients including diclofenac in a solution comprising DMSO as penetration enhancer along with glycerol, propylene glycol and water.
US Patent No. 5,093,133 describes the method for preparing hydro alcoholic gel of Ibuprofen for percutaneous delivery. The gel comprises ibuprofen along with alcohol, non-volatile solvent and gelling agents.
US Patent Nos. 5,318,960 and 5,985,860 describes a composition for pain relieving NSAID's like ibuprofen, methotrexate, capsaicin, diphenhydramine, methylnicotinate, indomethacin, ketoprofen, aspirin, diclofenac sodium, etc and combinations thereof
2

produced for transdermal delivery. The compositions are manufactured by add mixing an appropriate amount of surfactant with an appropriate amount of co-solubilizers alcohol to establish a non-aqueous phase. There after an appropriate amount of distilled water is slowly added to form a clear oil continuous solution.
US Patent No. 5,654,337 relates to a composition of pharmaceutically active substance including anti-inflammatory agent in a formulation, which is rapidly absorbed through the skin. The formulation comprises a polar lipid like lecithin, surfactant, water and urea with a pH of about 6-8.
US Patent No. 6,054,484 describes transparent aqueous solution of diclofenac sodium dissolved in a mixed solvent of a fatty acid dialkylolamide and water. The aqueous solution claims to have higher penetration.
US Patent No. 6,193,996 describes a pressure sensitive skin adhesive for transdermal delivery of diclofenac. The formulation incorporates effective amount of diclofenac or its pharmaceutically acceptable salts in the mixture of adhesives with penetration enhancer.
W09857624 discloses an invention of pharmaceutical preparation for topical application containing alcohol along with short chain n-alkylpyrolidone and at least one pyrolidone substituted with long chain alkyl radical and water quantity sufficient.
Diclofenac or its pharmaceutically acceptable salts and other NSAIDs produce their antiinflammatory analgesic action through inhibition of prostaglandin synthesis. On the other hand, counter irritants like menthol and methyl salicylate produce the sensation of heat at the site of application due to the increased blood circulation in the tissue. This mechanism of action helps alleviate pain and inflammation. Combination of diclofenac or its pharmaceutically acceptable salts with counter irritants have been formulated in the form of creams and gels to take advantage of various mechanisms of action of diclofenac and counter irritants. Combinations of diclofenac salts with counter irritants are available in the form of creams, gels and aerosols.
3

As it is apparent from the prior art that there have been a variety of approaches to enhance the penetration of diclofenac or its pharmaceutical acceptable salts as well as other NSAIDs. However, the preparation in all the prior arts incorporates water as one of the ingredients. One of the reasons for incorporating water in topical formulations such as creams and gels is to provide hydration, which is considered important for penetration of the active ingredients by hydrating the stratum corneum. More importantly water is used for its solubilizing property. Typical creams are prepared by dissolving water-soluble ingredients in the aqueous phase and the oil soluble ingredients in the oily phase. The two phases are mixed along with suitable surfactant to form a cream. Gels on the other hand only have aqueous phase and hence only water-soluble ingredients are incorporated. In case of aqueous solutions, water is used along with other co solvents and surfactants to solubilize the water-soluble ingredients of the formulation and also as a hydrating agent for the skin and in some cases water also helps reduce the viscosity of the solution.
Furthermore, pharmaceutically acceptable salts of diclofenac are susceptible to oxidation. Since commonly used antioxidants like sodium metabisulphite, sodium sulphite, etc are water-soluble, water provides a suitable medium to incorporate the antioxidants in the aqueous solution of diclofenac.
In case of creams and gels, due to the semisolid nature of the preparations, the amount of diclofenac that comes in contact with air is very much limited once the preparations are packed in suitable containers. However in case of aqueous solutions containing pharmaceutically acceptable salts of diclofenac, the movement of the topical solution within the container causes enough oxygen to dissolve in the solution and cause oxidative degradation of diclofenac salts resulting in yellow coloration. Although, water is an important ingredient for topical formulations of diclofenac salts for the aforementioned reasons, formulations comprising diclofenac and containing water will posses comparatively lesser stability than the non-aqueous diclofenac formulation.
Therefore, there exists a need to formulate a stable, low viscous, non-aqueous, non-greasy topical solution comprising diclofenac or its pharmaceutically acceptable salts
4

diclofenac with an enhanced penetration of diclofenac into skin at the site of application of said topical solution.
Description of the Invention
It is an aspect of the present invention to provide a stable, low viscous, non-aqueous, non-greasy topical solution comprising diclofenac or its pharmaceutically acceptable salts, which exhibits enhanced transdermal absorption resulting in higher blood levels of diclofenac or its salts when compared to the formulations known in the art as creams, lotions, aqueous gels or aqueous solutions.
In accordance with another aspect of the present invention, there is a topical solution comprising diclofenac or its pharmaceutically acceptable salts, wherein the solution comprises of diclofenac along with effective combination of propylene glycol, alcohol, penetration enhancers or other pharmaceutically acceptable excipients and optionally one or more humectants.
In accordance with one other aspect of the present invention, there is a topical solution comprising diclofenac or its pharmaceutically acceptable salts, wherein said diclofenac is further used in the combination with other pharmaceutically acceptable active ingredients selected from anti-coagulants, anesthetics or counterirritants.
Suitable anticoagulants herein used comprises of agatroban, cilostazol, citicoline, clopidogrel, cromafiban, dexanabinol, dicoumarol, dipyridamole, nicoumalone, oprevelkin, ozagrel, perindopril erbumine, phenindione, ramipril, repinotan, ticlopidine, tirofiban, and heparin, including heparin salts formed with organic or inorganic bases, and low molecular weight hssseparin, i.e., heparin fragments generally having a weight average molecular weight in the range of about 1000 to about 10,000 D and exemplified by enoxaparin, dalteparin, danaproid, gammaparin, nadroparin, ardeparin, tinzaparin, certoparin, and reviparin, but not limited to the above mentioned.
5

Suitable anesthetic herein used comprises of bupivacaine, chloroprocaine, oxyprocaine, mepivacaine, piperocaine, tetracaine, procaine, dibucaine, benzocaine, dyclaine and salts thereof, but not limited to the above mentioned.
Suitable counterirritants herein used comprises of camphor oil, white, camphor powder synthetic technical, eucalyptol, eucalyptus oil, eucalyptus citriodora, menthol crystals, methyl cedryl ketone, methyl chavicol and methyl salicylate, but not limited to the above mentioned.
Suitable pentration enhancers herein used comprises of sulphoxides (such as dimethylsulphoxide, DMSO), Azones (e.g. laurocapram), pyrrolidones (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes; Cyclodextrins, and cyclodextrin derivatives; but not limited to the above mentioned.
Suitable humectants herein used comprises of include, but are not limited to the following materials acetamide MEA, aloe vera gel, arginine PCA, chitosan PCA, copper PCA, corn glycerides, dimethyl imidazolidinone, fructose, glucamine, glucose, glucose glutamate, glucuronic acid, glutamic acid, glycereth-7, glycereth-12, glycereth-20, glycereth-26, glycerin, honey, hydrogenated honey, hydrogenated starch hydrolysate, hydrolyzed corn starch, lactamide MEA, lactic Acid, lactose lysine PCA, mannitol, methyl gluceth-10, methyl gluceth-20, PCA, PEG-2 lactamide, PEG-10 propylene glycol, polyamino sugar condensate, potassium PCA, propylene glycol, propylene glycol citrate, saccharide hydrolysate, saccharide isomerate, sodium aspartate, sodium lactate, sodium PCA, sorbitol, TEA-lactate, TEA-PCA, urea, xylitol, and the like, as well as mixtures thereof, but not limited to the above mentioned
Suitable solvents herein used comprises of ethers of polyethylene glycols, such as tetrahydrofurfuryl alcohol PEG ether (glycofurol, available commercially from BASF under the trade name Tetraglycol) or methoxy PEG (Union Carbide); amides, such as 2-
6

pyrrolidone, 2-piperidone, s-caprolactam, N-alkylpyrrolidone, N-
hydroxyalkylpyrrolidone, N-alkylpiperidone, N-alkylcaprolactam, dimethylacetamide, and polyvinylpyrrolidone; dimethyl acetamide, dimethyl isosorbide (Arlasolve DMI (ICI)), N-methyl pyrrolidones (Pharmasolve (ISP)), monooctanoin, diethylene glycol monoethyl ether (available from Gattefosse under the trade name Transcutol), but not limited to the above mentioned.
The present invention also provides the use of a device for applying said liquid formulation/composition to a desired area. The invention also provides for the massage of the desired area with the Roll on head of the device, after the application of liquid formulation/composition, without discharging additional liquid from the device, during the massage.
Example 1
Composition of non-aqueous solution of Diclofenac or its pharmaceutically acceptable salts (Without Counter Irritants):

S.No. Ingredients used Amount of the ingredient used
1 Diclofenac or its pharmaceutically acceptable salts 2.32% w/w10%w/w2% w/w
2 Ethanol
3 Oleic Acid
4 Propylene glycol Q.S
Procedure:
Ethanol and Oleic Acid are mixed and Diclofenac is dissolved in it. Then Propylene
glycol is added Q.S and stirred well.
7

Example 2
Composition of non-aqueous solution of Diclofenac or its pharmaceutically acceptable salts (With Counter Irritants'):

S.No. Ingredients used Amount of the ingredient used
1 Diclofenac or its pharmaceutically acceptable salts 2.32% w/w10% w/w 20% w/w 10% w/w
2 Ethanol
3 Methyl salicylate
4 Menthol
5 Propylene glycol Q.S
Procedure:
Diclofenac is dissolved in propylene glycol. Menthol and methyl salicylate are dissolved in Ethanol. The Ethanolic solution is then gradually added to the solution of Diclofenac in propylene glycol and the volume adjusted with Propylene glycol.
Example 3
Composition of non-aqueous solution of Diclofenac or its pharmaceutically acceptable salts:

S.No. Ingredients used Amount of the ingredient used
1 Diclofenac or its pharmaceutically acceptable salts 1.16% w/w15% w/w 20% w/w 10% w/w
2 Ethanol
3 Methyl salicylate
4 Menthol
5 Oleic Acid 2% w/w
8

6 Isopropyl myristate 1% w/w
7 Glycerol 1% w/w
8 Propylene glycol Q.S
Procedure:
Dissolve Diclofenac in Propylene glycol (around 10%). Dissolve Menthol in Methyl salicylate. Dissolve Glycerol in part of Ethanol (around 5%). Dissolve Isopropyl myristate in part of Ethanol (around 5%). Add 5% Ethanol to the solution of Methyl salicylate and Menthol. To this add the solution of Glycerol in Ethanol. To the resultant solution add the solution of Isopropyl myristate in Ethanol. Next add the solution of Diclofenac in Propylene glycol. Finally adjust the volume with Propylene glycol.

While this provisional patent application contains the description of the principal inventive concepts. The complete patent application pursuant here to, will fully and particularly describe the preferred embodiments of the present invention.

A NOVEL COMPOSITION OF NON-AQUEOUS TOPICAL SOLUTION

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