FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
Provisional Specification
[See Sections 10 and rule 13]
TITLE: Aceclofenac Gel and process for preparation thereof
Applicant: (a) Intas Pharmaceutical Limited
(b) Nationality: Indian
(c) Chinubhai Centre, Ashram Road Ahmedabad- 380009 Gujarat. India.
The following specification describes the invention:

FIELD OF THE INVENTION
The present invention relates to gel formulation of non steroidal antiinflammatory drug(s) or analgesic. The dosage form comprises anti-inflammatory or analgesic drug preferably aceclofenac or its pharmaceutically acceptable salts or derivatives, with other pharmaceutical ingredients which acts as antiinflammatory like methyl salicylate, menthol, linseed oil and capsaicin, pharmaceutically acceptable solvent and optionally other pharmaceutical excepients. The present invention also relates to a process of preparing aceclofenac gel formulation.
BACKGROUND AND PRIOR ART
Non-steroidal anti-inflammatory or analgesic drugs like aceclofenac and diclofenac are known to be used for chronic joint diseases, like rheumatoid arthritis, osteoarthrosis and ankylosing spondylitis, spondilytis as well as for detnalgia, postoperation pain or post-delivery pain. These are having superior prostaglandin inhibition effect compared to other anti-inflammatory analgesic drugs.
Non-steroidal anti-inflammatory or analgesic drugs particularly inhibit the production of interleukin-1 causing the destruction of joint cartilage and promotes the production of glycosaminoglycan found in joint cartilage, thus preventing rheumatoid arthritis, osteoarthrosis and the like from being worse.
WO2005032516 disclosed method for solubilizing aceclofenac using a self-microemulsifying drug delivery system dissolving aceclofenac in a mixed solvent of a hydrophilic solubilizing agent, a surfactant, a stabilizer and oil. The emulsified liquid is filled into the capsule.


WO2003004060 discloses the compressed formulation comprising active pharmaceutical ingredient aceclofenac with water insoluble polymer.
WO 2006054135 discloses the ready to use injectable formulation comprising aceclofenac salt with solubilizer and stabilizer. The stabilizer used in this patent is to stabilize aceclofenac and diclofenac that forms by conversion of aceclofenac thereto and also aceclofenac stabilizer used which is effective to inhibit precipitation of aceclofenac free acid.
Aceclofenac has a tendency to get converted into diclofenac in aqueous formulation.
Sometimes injection is not convenient to the patient, and also difficult to administer to some patients. Further injection is not self administrable. For beneficial effect of the drug, use of minimum exceipents and to overcome the administrative difficulties, in the present invention a gel formulation of aceclofenac is prepared, which is administered topically without any inconveniency or difficulty in dose administration. Also in the present invention conversion of aceclofenac into diclofenac is avoided by using non aqueous solvents and by use of polymers that gel in the said solvent.
OBJECTS OF THE INVENTION
The first object of the present invention is to provide stable gel formulation of aceclofenac.
Another object of the present invention is to provide stable gel formulation of aceclofenac alone or in combination with ingredient which act as antiinflammatory agent such as methyl salicylate, Menthol, Linseed Oil, Capsaicin.


Another purpose is to avoid conversion of Aceclofenac into diclofenac.
Yet another object of the present invention is to develop a process to prepare stable gel formulation of aceclofenac suitable for topical administration at the affected site over skin.
SUMMARY OF THE INVENTION
The present invention relates to stable gel formulation of non-steroidal antiinflammatory or analgesic drugs or analgesic drug preferably aceclofenac. The dosage form comprises active pharmaceutical ingredient (drug), solvent and optionally other pharmaceutical excipients. The present invention also relates to a process of preparing aceclofenac gel formulation.
DESCRIPTION OF INVENTION
According to the present invention stable gel formulation of anti-inflammatory or analgesic drug preferably aceclofenac comprises drug preferably aceclofenac or its pharmaceutically acceptable salt alone or in combination with ingredients which act as anti-inflammatory agent such as methyl salicylate, Menthol, Linseed Oil, Capsaicin and the like pharmaceutically acceptable solvent and optionally other pharmaceutically acceptable excipients.
Aceclofenac has tendency to get converted into diclofenac in presence of water or aqueous media. Hence, in the present invention water or aqueous media is completely replaced with non aqueous one to avoid conversion of aceclofenac into diclofenac.


The anti-inflammatory ingredient in the present invention ranges from 10 to 70 %w/w.
The anti-inflammatory ingredient preferably aceclofenac present in this pharmaceutically composition is in amounts ranging from 0.1 to 5 %w/w alone or in combination with one or more ingredients selected from the group comprising of methyl salicylate ranges from 0.5 to 50 %w/w, menthol 1 to 20 %w/w, linseed oil 0.1 to 10 %w/w, capsaicin 0.01 - 0.05%w/w and the like.
The pharmaceutically acceptable solvent or vehicle or solubilizer used in the present pharmaceutically composition is selected from the group comprising but not limited to ethanol, isopropyl alcohol, propylene glycol, propylene glycerine and the like, which in amount ranges q.s. to 100%
Anti-oxidant used in the present invention is in an amount ranging from 0.01 -2%w/w. The anti-oxidant is selected from the group comprising but not limited to of butylated hydroxytoluene, butylated hydroxy anisole, sodium metabisulfite, sodium sulfite, sodium bisulfite, citric acid, ascorbic acid and the like.
The pharmaceutically acceptable polymer used for gelling in the present invention ranges from 0.5 to 10 %w/w selected from the group comprising but not limited to poloxomer, hydroxypropyl cellulose, carbopols and the like or combination thereof.
Preservative is used to prevent microbial contamination and make the formulation stable for longer duration. The preservative ranges from 0.5 to 5 %w/w can be

selected from the group but not limited to benzyl alcohol, sodium nenzoate, methylparaben, propylparaben, ethylparaben, sodium benzoate, potassium sorbate, sorbic acid and the like.


Throughout this specification it is to be understood that the words "comprise" and "include" and variations such as "comprises", "comprising", "includes", "including" are to be interpreted inclusively, unless the context requires otherwise. That is, the use of these words may imply the inclusion of an element or elements not specifically recited.
Example
The present invention has been described by way of example only, and it is to be recognized that modifications thereto falling within the scope and spirit of this specification, and which would be obvious to a person skilled in the art based upon the disclosure herein, are also considered to be included within the scope of this invention.
The formulation of the present invention is a topical gel can be illustrated as follow:

s.No. Category Range (%w/w)
1. Active Ingredient 2-70 %
2 Preservative 0.5 - 5%
3 Anti oxidant 0.01-2%
4 Gelling polymer 0.5-10%
5 Solubilizer / Solvent / Vehicle q.s. to 100%


The present invention can be illustrated by but not limited to following example(s).
Example 1

Sr. No. Ingredient % w/w
1. Aceclofenac 1.0
2. Methyl salicylate 7.5
3. Menthol 3.0
4. Linseed Oil 4.0
5. Capsaicin 0.005
6. Benzyl Alcohol 2.0
7. Butylated HydroxyToluene 0.3
8. Carbopol 940 5.0
9. Propylene glycol q.s. to 100%
Example 2

Sr. No. Ingredient % w/w
1. Aceclofenac 1.5
2. Methyl salicylate 10.0
3. Menthol 5.0
4. Linseed Oil 3.0
5. Capsaicin 0.01
6. Benzyl Alcohol 2.0
7. Butylated HydroxyToluene 0.3
8. Carbopol 940 5.0
9. Propylene glycol q.s. to 100%


Example 3

Sr. No. Ingredient % w/w
1. Aceclofenac 2.0
2. Methyl salicylate 5.0
3. Menthol 7.5
4. Linseed Oil 1.0
5. Capsaicin 0.02
6. Benzyl Alcohol 1.5
7. Butylated Hydroxy Toluene 0.1
8. Hydroxypropylcellulose (Klucel MF) 5.0
9. Ethanol q.s. to 100%
Process for preparation:
a) Take approx. 60g of Ethanol in the container and add and dissolve Aceclofenac till clear solution is obtained.
b) Add and dissolve Methylsalicylate to the solution of step a) till clear solution is obtained.
c) Add and dissolve Menthol to the solution of step b) till clear solution is obtained.
d) Add Linseed oil drop wise to the solution of step c) and stir till clear solution is obtained.
e) Add and dissolve Capsaicin to the solution of step d) till clear solution is obtained.
f) Add and dissolve Butylated Hydroxytoluene (BHT) to the solution of step e) till clear solution is obtained.
g) Add and dissolve Benzyl Alcohol to the solution of step f) till clear solution is obtained.
h) Take hydroxypropyl cellulose (Klucel MF) and pass through Sieve #40 and add very slowly to the solution of step g) with homogenization till clear gel is formed.


i) Add ethanol to the gel formed in step h) to makeup weight to the desired batch size.
Dated this 7th day of November 2007.



To,
The Controller of Patent, The Patent Office At Mumbai