FIELD OF INVENTION The present invention relates to amorphous ziprasidone hydrochloride of formula (I) and process for preparation thereof.

BACKGROUND OF THE INVENTION Ziprasidone hydrochloride of formula (I), chemically known as 5-[2-[4-(1 ,2- benzisothiaol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydr o-2H-indol-2-one hydrochloride is a potent seretonin and dopamine antagonist, effective as an antipsychotic drug with negligible side effects for treating various disorders including schizophrenia, anxiety, migraine etc.

Ziprasidone hydrochloride is commercially sold under the brand names of Zeldox, Geodon etc for oral administration.

Ziprasidone and its acid addition salts, including the hydrochloride salt was first disclosed by Lowe J.A. et. al in US Patent No. 4 831 031. This patent discloses a method for preparation of the ziprasidone hydrochloride hemihydrate by solvent precipitation method comprising addition of diethyl ether containing dissolved hydrogen chloride gas to a solution of ziprasidone in methylene chloride.

There is no mention in the above patent about the solid-state characteristics of ziprasidone hydrochloride to indicate whether ziprasidone hydrochloride is crystalline or amorphous. US Patent No. 5 312 925 (Allen J.M.A et. al) discloses a method for preparation of crystalline ziprasidone hydrochloride monohydrate by heating an aqueous mixture of ziprasidone free base in presence of concentrated hydrochloric acid at 60-65°C. This patent provides x-ray powder diffraction and infra-red spectral data indicating the crystalline nature of ziprasidone hydrochloride monohydrate.

US Patent No. 6 110 918 (Busch F.R. et. al) discloses a method for preparation of mesylate trihydrate salt by addition of an aqueous solution of methanesulfonic acid to a slurry of ziprasidone free base in an organic solvent followed by formation of the mesylate salt under reflux. The presence of the mesylate salt in four distinct forms viz. trihydrate, dihydrate (lath), dihydrate (needle), and anhydrous form is indicated by x-ray diffraction powder spectrum.

The present invention relates to method for preparation of ziprasidone hydrochloride, which is substantially amorphous and of high purity and stability.

OBJECT OF THE INVENTION The object of the present invention is to provide an efficient and economically advantageous process for preparation of ziprasidone hydrochloride of formula (I), which is substantially amorphous and of high purity and stability.

SUMMARY OF THE INVENTION An aspect of the invention relates to ziprasidone hydrochloride of formula (I), which is substantially amorphous and of high purity and stability.

Another aspect of the invention relates to providing a process for preparation of substantially amorphous ziprasidone hydrochloride of formula (I), by different methods such as spray-drying, lyophilisation, freeze drying, solvent precipitation, jet-milling etc.

In a preferred embodiment, amorphous ziprasidone hydrochloride is be prepared by spray drying a solution of of ziprasidone hydrochloride in a mixture of alcoholic solvent such as methanol, ethanol, isoproanol, or tert-butyl alcohol with acetonitrile.

In a particularly preferred embodiment, the solution of ziprasidone hydrochloride is prepared in a mixture of methanol and acetonitrile. The amount of methanol is used in an amount of 3-5 times the volume of acetonitrile, preferably, 4 times the volume of acetonitrile.

The solution of ziprasidone hydrochloride is spray dried maintaining the inlet temperature between 70 to 90 0C and outlet temperature between 50 to 75 0C.

BRIEF DESCRIPTION OF ACCOMPANYING DRAWING Figure 1 : X ray diffraction pattern of the amorphous form of compound of formulai obtained by spray drying of present invention.

DETAILED DESCRIPTION OF ACCOMPANYING DRAWING The X-ray powder diffraction pattern of the product obtained by spray drying is as depicted in Fig.1. It is without any diffraction peaks. This demonstrates amorphous nature of the product formed by the process of present invention.

For example, a substantially amorphous form of ziprasidone hydrochloride of formula (I) having high purity and stability could be prepared by utilizing the method of spray-drying given below: Example-01 Ziprasidone hydrochloride (10gms) was dissolved in a mixture of acetonitrile (725ml) and methanol (2900ml). The resulting mixture was spray dried at a temperature between 65°C and 9O0C. The product separating out was dried at ambient temperature to give substantially amorphous ziprasidone hydrochloride. Yield: 4.0gms.