FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
TITLE OF THE INVENTION:
NOVEL PROCESS FOR PREPARATION OF POLYMORPHIC MIXTURE OF
DESLORATADINE
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 relates to novel process for preparation of polymorphic mixture of desloratadine
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 process for preparation of polymorphic mixture of desloratadine. More particularly present invention provides a process for preparation of a mixture of a crystalline desloratadine Form I which contains Form II in specific range 15 - 30%.
Chemically desloratadine is 8-Chloro-6, 11-dihydro-11-(4-piperidinylidene)-5/-/-benzo [5,6] cyclohepta[1,2-6]pyridine having structure as depicted in Formula 1. Desloratadine is Histamine Hi-receptor antagonist and active metabolite of loratadine. It is indicated for the treatment of allergic reaction in mammals

Formula I
US patent no. 4,659,716 provides a process for preparation of desloratadine by alkaline hydrolysis of loratadine followed by treatment with acetic acid to give the acetate salt of desloratadine, and then converting the acetate into the free base of desloratadine.
US patent no. 6,506,767 discloses the polymorphic forms of desloratadine. The XRPD peaks and the FTIR spectrum for the forms are also disclosed in the 767 patent
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Other methods of preparing desloratadine are disclosed in US 3,326,924, US 4,282,233 patents and PCT patent application WO 04/029039
US 200400242619, US 20040229896 and US 20060135547 patent applications disclose polymorphic desloratadine having a specific XRD pattern.
US application No. 20060058334 provides substantial pure desloratadine having HPLC purity greater than 99.5%
The present inventors surprisingly found that by dissolving desloratadine in alcohol-water provides a simple process for preparation of a mixture of crystalline Form I of desloratadine having Form II in the range of 15 to 30%. Such polymorphic mixture offers similar biological and pharmaceutical profile as compared to pure polymorphic forms I and II.
In one aspect of the present invention there is provided a process for preparation of a crystalline desloratadine Form I having less than 30% of Form II, wherein the said process comprises of
a) dissolving desloratadine in an alcohol,
b) seeding the resultant mass with Form I containing less than 30% of Form II seed,
c) optionally removing alcohol from the reaction mixture thereof,
d) isolating crystalline desloratadine Form I having less than 30% of Form II by adding water to the reaction mixture thereof.
Desloratadine used can be prepared by methods known in the art. Desloratadine is dissolved in alcohol at temperature above 50°C. It was then cooled to ambient temperature and optionally seeded with desloratadine containing 15-30% of Form II in Form I. The resultant reaction mixture was concentrated under vacuum and product is precipitated by addition of water. The precipitated product was
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filtered washed and dried to get the desloratadine having constant mixture form II in the range of 15-30% in form I.
The suitable alcohol may be selected from a group comprising one or more of d-C4 linear chain or branched chain alcohols such as methanol, ethanol, isopropyl alcohol and the like.
Powder XRD of the samples were 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.
EXAMPLE
Preparation of Desloratadine constant polymorphic mixture
Desloratadine (445 gm) was charged with Isopropyl alcohol (2.25 L). Heat the reaction mixture to 60°C to get clear solution. It was then cooled to room temperature and seeded with desloratadine (mixture of polymorph II 25% in form-I, 8 gm,) stirred the reaction mixture and concentrated under reduced pressure to remove alcohol. The water (3.15 L) was added to the reaction mass and titled product was filtered, washed and dried. Yield: 435 g Desloratadine form II: 18.16% by XRD
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1. A process for preparation of a crystalline desloratadine Form I having less than
30% of Form II, wherein the said process comprises of
a) dissolving desloratadine in an alcohol,
b) seeding the resultant mass with Form I containing less than 30% of Form II seed,
c) optionally removing alcohol from the reaction mixture thereof,
d) isolating crystalline desloratadine Form I having less than 30% of Form II by adding water to the reaction mixture thereof.

2. A process according to claim 1 wherein the alcohol is one or more of C1-C4 linear chain or branched chain alcohols.
3. Crystalline desloratadine Form I having less than 30% of Form II having characteristic powdered X-Ray Diffraction (XRD) pattern as depicted in Fig1.
Dated this2^m day of September, 2006 For Wockhardt Limited
WE CLAIM:


(Mandar Kodgule) Authorized Signatory 5