FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:
TOPICAL COMPOSITIONS COMPRISING KETOTIFEN OR SALT THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra
(East), Mumbai - 400 051.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides topical composition comprising of ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers.
The following specification particularly describes the invention and the manner in which it is to be performed.
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4. Description
The present invention provides a topical composition comprising of ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers.
Ketotifen fumarate is a finely crystalline powder with an empirical formula of C23H23NO5S and a molecular weight of 425.50. Its chemical name is 4-(1-Methyl-4-piperidylidene)-4H-benzo[4,5] cyclohepta [1,2-b] thiophen-10 (9H)-one hydrogen fumarate. It is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis.

US Patent No 6,774,137, 6,777,429 and US application 2006148899, 2006089384 describe an ophthalmic composition comprising ketotifen salt.
US Patent No 6,776,982 and 6,468,548 describe an autoclavable ophthalmic composition comprising ketotifen and method of stabilizing such compositions.
US Patent No. 6,455,547 and 6,576,649 describes a method for stabilizing a pharmaceutical composition by using plastic containers comprising an antioxidant.
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US Application 2005239745 describes topical formulations of anti-allergenic agents.
In one of the aspects of the present invention there is provided a topical composition comprising of ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers.
In another aspect of the present invention there is provided a topical composition comprising ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein ketotifen is present in admixture with cyclodextrins or derivatives thereof.
In yet another aspect of the present invention there is provided a topical composition comprising ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein ketotifen is present in the form of complex with cyclodextrins or derivatives thereof.
The topical composition of the present invention can be administered as otic, nasal or ophthalmic solution or can also be present in the form of lotion, liniment, cream, ointment and skin pour on.
The topical composition of the present invention comprises of ketotifen or salt thereof, wherein ketotifen can be present in the form of ketotifen fumarate.
The ketotifen ophthalmic solution can be prepared by mixing ketotifen with cylcodextrin and adding it to the solution of all other pharmaceutically acceptable ingredients.
The complex of ketotifen and cyclodextrin can be prepared by various processes including solvent evaporation, kneading, spray drying, colloidal milling, high speed mixing, trituration or simple mixing. The ketotifen can be present in an
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amount relative to the cyclodextrin, such that a molar ratio between the ketotifen and the cyclodextrin is from about 1:1 to 1:10. Ketotifen or salt thereof may be added to the formulation in the form of complex.
Exterior portion of cyclodextrin being hydrophilic allows the cyclodextrin to form inclusion complexes with ketotifen and which can then be dissolved in water.
Suitable cyclodextrin derivatives may be selected from hydroxypropyl-b-cyclodextrin, b-cyclodextrin, a-cyclodextrin, hydroxypropyl- a-cyclodextrin and the like.
Pharmaceutically acceptable carriers may include preservatives, chelating agents, tonicity adjusting agents, buffering agents, and viscosity enhancers.
Suitable preservatives may be selected from a group comprising one or more of benzalkonium chloride, phenylmercuric acetate, chlorobutanol, benzyl alcohol, parabens, thiomersal and the like.
Suitable chelating agents may be selected from a group comprising one or more of edetate salts like edetate disodium, edetate calcium disodium, edetate sodium, edetate trisodium, and edetate dipotassium.
Suitable tonicity adjusting agents may be selected from a group comprising one or more of mannitol, sorbitol, sodium chloride, sodium borate, glycerol, propylene glycol, dextrose and the like.
Suitable buffering agents may be selected from a group comprising one or more of acetate, ascorbate, hydrogen carbonate/carbonate, citrate, gluconate, lactate, phosphate, propionate, tromethamine and the like.
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Suitable viscosity enhancers may be selected from hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone and the like.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
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EXAMPLE-I
Table 1 - Ketotifen fumarate ophthalmic solution

Sr.No Ingredients % Composition
1 Ketotifen fumarate Eq. to ketotifen 0.025%
2 ydroxy propyl betacyclodextrin 0.5 to 2.0%
3 Polyvinyl Alcohol 0.1 to 1.4%
4 Disodium EDTA 0.001 to 0.5%
5 Sodium Chloride 0.01 % to 0.9%
6 Benzalkonium Chloride 0.002% to 0.04%
7 Water For injection q.S. 100%
Procedure:
Polyvinyl alcohol is dissolved in water. Disodium EDTA, sodium chloride and benzalkonium chloride are added to this solution. Ketotifen and hydroxypropyl betacyclodextrin are mixed together and added to above solution. pH of the final solution is adjusted between 4.4-7.0 by using suitable pH adjusting agent and osmolality is in the range of 230-330 mOsm. Solution is filtered through 0.22mm filter and filled in suitable container and capped.
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WE CLAIM:
1. A topical composition comprising of ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers.
2. A topical composition comprising of ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein ketotifen is present in admixture with cyclodextrins or derivatives thereof.
3. A topical composition comprising of ketotifen or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein ketotifen is present in the form of complex with cyclodextrins or derivatives thereof.
4. A topical composition according to claims 1, 2 and 3 is otic solution, nasal solution, ophthalmic solution, lotion, liniment, cream, ointment and skin pour on.
5. A topical composition according to claims 1, 2 and 3 wherein the ketotifen is present in the form of ketotifen fumarate.
6. A topical composition according to claims 1, 2 and 3 wherein the cyclodextrins
are selected from the group comprising one or more of hydroxypropyl-b-cyclodextrin, b-cyclodextrin, a-cyclodextrin, hydroxypropyl- a-cyclodextrin and the like.
7. A topical composition according to claims 1, 2 and 3, wherein the carrier
component comprises water.
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8. A topical composition according to claim 1, 2 and 3, wherein pharmaceutical^ acceptable carriers comprise preservatives, chelating agents, tonicity adjusting agents, buffering agents, viscosity enhancers.


Dated this 27TH day of December, 2006

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