FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
NOVEL POLYMORPHIC FORM 'W-l' OF ANHYDROUS AZITHROMYCIN
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 novel polymorphic form 'W-l' of anhydrous azithromycin.
following specification particularly The describes the invention and the manner in which it is to be performed.
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4. DESCRIPTION
The present invention provides novel polymorphic form 'W-l' of azithromycin. More particularly the present invention provides novel anhydrous azithromycin polymorphic form 'W-l1.
A/-methyl-11-aza-10-deoxo-10-dihydroerythromycin A, known by its generic name Azithromycin of Formula I, is a broad-spectrum semi-synthetic macrolide antibiotic compound belonging to the erythromycin A family.

Formula-I
The processes for preparation of Azithromycin are disclosed in the U.S. patent 4,517,359 and U.S. patent 4,474,768. The ring expansion of erythromycin-A and subsequent conversion to azithromycin is described in the 768 patent.
U.S. patent 4,963,531 provides a process for preparing azithromycin dihydrate. The '531 patent further provides that on storage at low humidity the azithromycin dihydrate loses water.
European Patent EP 1313749 B1 provides a method for preparation of azithromycin which comprises removing an organic solvent from the solution comprising the hydrated compound in the organic solvent or a solution of the hydrated compound in a mixture of the organic solvent and water so as to provide anhydrous compound.
U.S. Patent No. 6,268,489 discloses azithromycin dihydrate as a crystalline form of azithromycin, which is stable and non-hygroscopic. The '489 patent also
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discloses azithromycin monohydrate as a crystalline form of azithromycin which is unstable and hygroscopic.
Several other processes for the preparation of azithromycin, intermediates useful in the preparation of azithromycin and different polymorphic forms of azithromycin are known in the art such as U.S. patent Nos. 4526889, 4963528, 4886792, 5686587, 5869629, 6013778, 6504017, 6420537, 6365574, 6703372, 6451990, 6586576, 6528492, 6936591, 6949519, 6268489, 5250518, 6977243, 7053192, 7081525, U.S. patent application Nos. 2003139583, 2004043944, 2004043945, 2004138149, 2004014951, 2005090459, 2005119468, 20050222052, 2006063725, 20050222052, 2006019908, 2006183890, PCT application Nos. WO 2002009640, WO 2005003144, WO 2007015265, WO 2007017898, WO2007029266.
There is a continuing need for preparing anhydrous azithromycin in novel polymorphic form that is useful for commercial purposes, substantially free of organic solvents and is stable.
The present inventors have developed an anhydrous azithromycin in a novel polymorphic form referred as polymorphic form 'W-l', which is stable, consistently reproducible and useful to make pharmaceutical compositions. It was surprisingly found that when anhydrous azithromycin is isolated from acetonitrile and dried under vaccum at 55-60°C; the anhydrous azithromycin was obtained in a novel polymorphic form.
In one of the aspect of the present invention there is provided a novel polymorphic form 'W-l' of anhydrous azithromycin having a characteristic XRD pattern as depicted in Figure I with the 2 theta values at 8.88, 11.20, 12.78, 13.40, 15.88, 17.80, 19.48, 23.22, 23.98 ± 0.2° 20.
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In another aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of the anhydrous azithromycin polymorphic form 'W-l' and one or more pharmaceutically acceptable excipient.
In another aspect of present invention provides the process of preparation of anhydrous azithromycin polymorphic form 'W-l'. The process includes step of:
a) combining the anhydrous azithromycin with the nitrile solvent
b) isolating anhydrous azithromycin from the reaction mass thereof.
c) drying the anhydrous azithromycin under vacuum at 55°-60°C.
Anhydrous azithromycin used as starting material can be prepared by the method known in the art. Anhydrous azithromycin obtained thereof was dissolved in nitrile solvent such as acetonitrile, propionitrile and the like. The reaction mixture was heated for complete dissolution and then cooled to 20°C or less. The precipitated product was isolated from the mixture thereof and dried under vaccum at 55-60°C to obtain anhydrous azithromycin polymorphic form 'W-l'. The novel polymorphic form is having purity 98% or more when measured by HPLC, and moisture content less than 0.5% when measured by Karl fisher reagent.
Powder XRD of the samples was determined by Rigaku X-Ray diffractometer model no. 2200-v Japan.
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
Preparation of anhydrous azithromycin polymorphic form 'W-l'
Anhydrous azithromycin (20.0 gm) was dissolved in acetonitrile (100.0 ml). The reaction mixture was heated at about 62°C to get clear solution. The reaction mixture was allowed to cool at 45-47°C to precipitate the product. The slurry obtained was further cooled to 20°C and stirred for one hour. Solid obtained was filtered and washed with acetonitrile and dried under vaccum at 55-60°C to get the titled compound. Yield: 17.0 gm Moisture: 0.32% Purity: 98.76%
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WE CLAIM:
1. Novel polymorphic form "W-l" of anhydrous azithromycin.
2. Anhydrous azithromycin of claim 1 having characteristics 2 theta values at 8.88, 11.20, 12.78, 13.40, 15.88, 17.80, 19.48, 23.22, 23.98 ± 0.2° 26.
3. A process of preparation of anhydrous azithromycin polymorphic form 'W-l'. The process comprising:

d) combining the anhydrous azithromycin with the nitrile solvent
e) isolating anhydrous azithromycin from the reaction mass thereof, c) drying of anhydrous azithromycin under vacuum at 55°-60°C.

4. A process of claim 3 wherein nitrile solvent is acetonitrile, propionitrile and the like.
5. Anhydrous azithromycin having moisture content less than 0.5%.
6. Anhydrous azithromycin having purity more than 98.5% or more when measured by HPLC.
7. A pharmaceutical composition comprising a therapeutically effective amount of anhydrous azithromycin polymorphic form'' W-l11' and one or more pharmaceutically acceptable carriers, excipient or diluents.

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