A NOVEL CRYSTALLINE FORM OF RISPERIDONE
FIELD OF THE INVENTION
The present invention relates to a novel crystalline form of risperidone, to a process for its preparation and to a pharmaceutical composition containing it.
BACKGROUND OF THE INVENTION
Risperidone, chemically 3-[2-[4-(6-Fluoro-1,2-ben2isoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one is known to be useful for the treatment of psychotic diseases. The chemical structure of risperidone is:

The synthesis and therapeutic uses of risperidone are disclosed in EP 0196132. Preparation of two crystalline forms of risperidone, form A and form B, are described in US 2002/0193386.
We discovered a novel crystalline form of risperidone. The novel crystalline form is stable and is not spontaneously converted to other forms of risperidone. The novel form is distinguishable from other forms by x-ray
diffractions.
The object of the present invention is to provide a novel crystalline form of risperidone, process for preparing it and a pharmaceutical composition containing it.

DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, there is provided a novel crystalline form of risperidone, designated as form C, characterized by an x-ray powder diffraction pattern having peaks expressed as 29 at about 6.8, 10.5, 11.3, 14.0, 14.7, 15.3, 16.3, 18.3, 18.8, 19.6, 21.1, 22.3, 23.0, 25.1, 28.3 and 28.8 degrees. Figure 1 shows typical form C x-ray powder diffraction pattern.
In accordance with the present invention, a process is provided for preparation of risperidone form C. Thus, risperidone is dissolved in a suitable solvent and risperidone form C is isolated from the solution. Risperidone in any crystalline form may also be used in the process. Risperidone form C can be isolated by the techniques like cooling, partial removal of the solvent, using an anti-solvent or combination thereof. The suitable solvents are selected from the group consisting of tetrahydrofuran, 1,4-dioxane, diethyl ketone and a mixture of methyl tert-butyl ether and dimethylformamide. Preferable solvents are 1,4-dioxane and tetrahydrofuran.
In accordance with the present invention, there is provided a pharmaceutical composition comprising form C of risperidone and a pharmaceutically acceptable carrier or diluent.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a x-ray powder diffraction spectrum of risperidone form C. x-Ray powder diffraction spectrum was measured on a Siemens D5000 x-ray powder diffractometer having a copper-Ka radiation.
The following examples are given for the purpose of illustrating the present invention and should not be considered as limitations on the scope or spirit of the invention.
Example 1 Risperidone (5.0 gm, obtained by the process described in example 5 of EP 0196132) is mixed with 1,4-dioxane (50 ml), heated to about 60°C and stirred for 1 hour at 60°C to 65°C. The solution obtained is slowly cooled to 25°G

and stirred for 6 hours at 25°C to 30°C. The contents are cooled to 0°C and the solid is isolated by filtration to give 3.1 gm of risperidone form C.
Example 2 Risperidone (5.0 gm, obtained by the process described in example 5 of EP 0196132) is mixed with tetrahydrofuran (25 ml), heated to about 56°C and the solution obtained is slowly cooled to 25°C and stirred for 2 hours at 25°C to 30°C. The contents are then cooled to 0°C and the solid is filtered off and dried to give 3.5 gm of risperidone form C.

We claim:
1. A crystalline risperidone form C, characterized by an x-ray powder diffraction pattern having peaks expressed as 29 at about 6.8, 10.5, 11.3, 14.0,14.7, 15.3, 16.3, 18.3, 18.8, 19.6, 21.1, 22.3, 23.0, 25.1, 28.3 and 28.8 degrees.
2. A crystalline risperidone form C as defined in claim 1, further characterized by an x-ray powder diffraction pattern as in figure 1.
3. A process for preparation of risperidone form C as defined in claim 1, which comprises the steps of:

a) dissolving risperidone in a suitable solvent; and
b) isolating risperidone form C from the solution;
wherein the suitable solvent is selected from the group consisting of tetrahydrofuran, 1,4-dioxane, diethyl ketone and a mixture of methyl tert-butyl ether and dimethylformamide.
4. A process according to claim 3, wherein suitable solvent is 1,4-dioxane.
5. A process according to claim 3, wherein suitable solvent is tetrahydrofuran.
6. A pharmaceutical composition comprising risperidone form C of claim 1 and a pharmaceutically acceptable carrier or diluent.