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 EPINASTINE 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 a topical composition comprising of epinastine 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 epinastine or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers.
Epinastine is an antiallergic medication and an inhibitor of histamine release from the mast cell for topical administration to the eyes with an empirical formula of Ci6H15N3 • HCI and a molecular weight of 285.78. Its chemical name is 3-Amino-9, 13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine hydrochloride. It is indicated for the prevention of itching associated with allergic conjunctivitis.

US Application 2003050303 describe a method for treating late phase reactions of allergic conjunctivitis using epinastine, or its pharmacologically acceptable acid addition salts.
US Application 2005239745 describes topical formulations of anti-allergenic agents.
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In one of the aspects of the present invention there is provided a topical composition comprising of epinastine 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 of epinastine or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein epinastine is present in admixture with cyclodextrins or derivatives thereof.
In yet another aspect of the present invention there is provided a topical composition comprising of epinastine or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein epinastine 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 epinastine or salt thereof, wherein epinastine can be present in the form of epinastine hydrochloride.
The epinastine ophthalmic solution can be prepared by mixing epinastine with cylcodextrin and adding it to the solution of all other pharmaceutically acceptable ingredients.
The complex of epinastine and cyclodextrin can be prepared by various processes including solvent evaporation, kneading, spray drying, colloidal milling, high speed mixing, trituration or simple mixing. The epinastine can be present in an amount relative to the cyclodextrin, such that a molar ratio between the
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epinastine and the cyclodextrin is from about 1:1 to 1:10. Epinastine 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 epinastine and which can then be dissolved in water.
Suitable cyclodextrin derivatives may be selected from hydroxypropyl-(3-cyclodextrin, p-cyclodextrin, a-cyclodextrin, hydroxypropyl- a-cyclodextrin and the like.
Pharmaceutical 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, tromeathamine 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 - Epinastine ophthalmic solution

Sr.No Ingredients % Composition
1 Epinastine hydrochloride Eq. to Epinastine 0.05 %
2 HPBCD (Hydroxypropyl Betacyclodextrin) 0.1 to 2%
3 Polyvinyl alcohol (PVA) 0.1 to 1.4%
4 EDTA Disodium 0.01 to 0.1 %
5 Sodium citrate 0.01 to 1.5
6 Citric acid 0.01 to 0.5%
7 Sodium chloride 0.01 to 0.9%
8 Benzalkonium Chloride 0.004 to 0.01%
9 Water For injection q.s. 100%
Procedure:
Polyvinyl alcohol is dissolved in water. Disodium EDTA, sodium chloride, citric acid and sodium citrate are added to this solution. Epinastine and hydroxypropyl betacyclodextrin are mixed together and added to above solution. Benzalkonium chloride is dissolved separately in a preheated vessel and added to above solution. pH of the final solution is adjusted between 4.5-7.0 by using suitable pH adjusting agent and osmolality is in the range of 230-330 mOsm. Solution is filtered through 0.22pm filter and filled in suitable container and capped.
EXAMPLE-II
Table 2 - Epinastine ophthalmic solution

Sr.No Ingredients % Composition
1 Epinastine hydrochloride Eq. to Epinastine 0.05 %
2 HPBCD (Hydroxypropyl Betacyclodextrin) 0.1 to 2%
3 Polyvinyl alcohol (PVA) 0.1 to 1.4%
4 EDTA Disodium 0.01 to 0.1 %
5 Dibasic sodium phosphate, dodecahydrate 0.1 to 2.0%
6 Monobasic sodium phosphate 0.01 to 1.0%
7 Sodium chloride 0.01 to 0.9%
8 Benzalkonium Chloride 0.004 to 0.01%
9 Water For injection q.s. 100%
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Procedure:
Polyvinyl alcohol is dissolved in water. Disodium EDTA, sodium chloride, monobasic sodium phosphate and dibasic sodium phosphate are added to this solution. Epinastine and hydroxypropyl betacyclodextrin are mixed together and added to above solution. Benzalkonium chloride is dissolved separately in a preheated vessel and added to above solution. pH of the final solution is adjusted between 4.5-7.0 by using suitable pH adjusting agent and osmolality is in the range of 230-330 mOsm. Solution is filtered through 0.22um filter and filled in suitable container and capped.
EXAMPLE-III
Table 3 - Epinastine ophthalmic solution

Sr.No Ingredients % Composition
1 Epinastine hydrochloride Eq. to Epinastine 0.05 %
2 HPBCD (Hydroxypropyl Betacyclodextrin) 0.1 to 2%
3 Polyvinyl alcohol (PVA) 0.1 to 1.4%
4 EDTA Disodium 0.01 to 0.1 %
5 Acetic acid 0.001 to 0.1%
6 Sodium acetate anhydrous 0.01 to 1.0%
7 Sodium chloride 0.01 to 0.9%
8 Benzalkonium Chloride 0.004 to 0.01%
9 Water For injection q.s. 100%
Procedure:
Polyvinyl alcohol is dissolved in water. Disodium EDTA, sodium chloride, acetic acid and sodium acetate are added to this solution. Epinastine and hydroxypropyl betacyclodextrin are mixed together and added to above solution. Benzalkonium chloride is dissolved separately in a preheated vessel and added to above solution. pH of the final solution is adjusted between 4.5-7.0 by using suitable pH adjusting agent and osmolality is in the range of 230-330 mOsm. Solution is filtered through 0.22pm filter and filled in suitable container and capped.
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WE CLAIM:
1. A topical composition comprising of epinastine or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers.
2. A topical composition comprising of epinastine or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein epinastine is present in admixture with cyclodextrins or derivatives thereof.
3. A topical composition comprising of epinastine or salt thereof along with cyclodextrins or derivatives thereof and other pharmaceutically acceptable carriers wherein epinastine 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 epinastine is present in the form of epinastine hydrochloride.
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-P-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 comprises of preservatives, chelating agents, tonicity adjusting agents, buffering agents, viscosity enhancers.


Dated this27™ day of December, 2006

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