FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

1. TITLE OF THE INVENTION
PROCESS FOR PURIFICATION OF EPINASTINE HYDROCHLORIDE
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Limited, D4-MIDC Area, Chikalthana,
Aurangabad - 431 210 (M.S.) INDIA.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a process for purification of epinastine hydrochloride. The present invention further provides pure epinastine hydrochloride.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention provides a process for purification of epinastine hydrochloride. The present invention further provides pure epinastine hydrochloride.
Epinastine hydrochloride is chemically known as 3-Amino-9,13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine hydrochloride and is represented by following formula (I).

Epinastine hydrochloride, marketed under the name ELESTAT, is an antihistamine. ELESTAT is indicated for the prevention of itching associated with allergic conjunctivitis.
There are several patents and patent applications cited in the literature, which refer to process for the preparation of epinastine such as U.S. Patent No. 4,313,931, U.S. Patent No. 6,403,790, U.S. Patent No. 5,312,916, EP Patent No. 35749, GB Patent No. 2071095 and WO 2001/40229.
The present inventors have developed an easy process for purification of epinastine hydrochloride by adding precipitating solvent to epinastine hydrochloride solution. The present inventors have found that epinastine hydrochloride obtained by this method has purity of 99.5 % or above when measured by HPLC.
In one aspect of the present invention there is provided a process for purification of epinastine hydrochloride, wherein the process includes steps of; (a) contacting epinastine hydrochloride with an organic solvent.
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(b) adding a precipitating solvent; and
(c) isolating pure epinastine hydrochloride from the reaction mass thereof.
The starting material epinastine hydrochloride can be obtained by the process known in the art for example as disclosed in US 4,313,931.
The process of present invention involves dissolving epinastine hydrochloride in an organic solvent and stirring this solution with activated carbon at 20-60 °C for 1 to 3 hours. The reaction mixture is filtered and filtrate is evaporated under pressure. The product obtained thereof is added with a precipitating solvent and stirred to produce a solid, which is isolated from the reaction mass thereof. Epinastine hydrochloride obtained by this method has purity of 99.5 % or above when measured by HPLC.
The non-limiting examples of organic solvents are polar protic, polar aprotic and halogenated solvents. The non-limiting examples of polar protic solvent include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, 2-methoxyethanol, or mixtures thereof. The non-limiting examples of polar aprotic solvent include tetrahydrofuran, dimethylsulfoxide, N,N-dimethylformamide, 1,4-dioxane, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, acetone, ethylmethyl ketone. The non-limiting examples of halogenated solvents include dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane and the like or mixtures thereof.
The non-limiting examples of a precipitating solvent include ether solvent and ester solvents. The non-limiting examples of ether solvent include dimethyl ether, diethyl ether, methyl-tert-butyl ether, diisopropyl ether, di-tert-butyl ether and the like or a mixture thereof. The non-limiting examples of ester solvents include methyl acetate, ethyl acetate, propyl acetate, butyl acetate, sec-butyl acetate, tert-butyl acetate, isoamyl acetate, isobutyl acetate, isopropyl acetate and the like or mixtures thereof.
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In another aspect of the present invention there is provided pure epinastine hydrochloride.
In this disclosure, epinastine hydrochloride with a purity of 99.5% or more is referred as pure epinastine hydrochloride.
The present invention is further illustrated by the following example which are provided merely to be exemplary of the invention and do not limit the scope of the invention. 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.
Example Purification of epinastine hydrochloride
Epinastine hydrochloride (57 gm) was added in methanol (250 ml). Activated carbon was added and stirred for 1 hour at 25-50 ° C. The reaction mixture was filtered through celite bed and was concentrated. To the reaction mass, ether (400 ml) was added with stirring. Filtered and washed with two volumes of ether and pure epinastine hydrochloride was isolated from the reaction mass thereof. Yield: 54.8gm. HPLC purity: 99-99.9 %.
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We claim:
1. A process for purification of epinastine hydrochloride, wherein the process
comprises steps of;
(a) contacting epinastine hydrochloride with an organic solvent.
(b) adding a precipitating solvent; and
(c) isolating pure epinastine hydrochloride from the reaction mass thereof.

2. A process of claim 1, wherein an organic solvent comprises of polar protic, polar aprotic and halogenated solvent.
3. A process of claim 2, wherein polar protic solvent include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, 2-methoxyethanol, or a mixture thereof.
4. A process of claim 2, wherein polar aprotic solvent include tetrahydrofuran, dimethylsulfoxide, N,N-dimethylformamide, 1,4-dioxane, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, acetone, ethylmethyl ketone or a mixture thereof.
5. A process of claim 2, wherein a halogenated solvent include dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane and the like or a mixture thereof.
6. A process of claim 1, wherein a precipitating solvent comprises of dimethyl ether, diethyl ether, di-tert-butyl ether, methyl-tert-butyl ether, diisopropyl ether, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, sec-butyl acetate, tert-butyl acetate, isoamyl acetate, isobutyl acetate, isopropyl acetate or a mixture thereof.
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7. Pure epinastine hydrochloride having a purity of 99.5% or more.




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Abstract
The present invention provides a process for purification of epinastine hydrochloride. The present invention further provides pure epinastine hydrochloride.
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