This application claims priority to Indian patent application no 3107/CHE/2009 filed on Dec 16, 2009 the contents of which are incorporated by reference in their entirety.

Field of invention:

The present invention relates to novel polymorphic form of Tiaprofenic acid. The present invention further relates to novel process for the preparation of crystalline polymorphic form of Tiaprofenic acid.

Back ground of the invention:

Tiaprofenic acid is a non-steroidal anti-inflammatory drug of the arylpropionic acid (profen) class, used to treat pain, especially arthritic pain. Tiaprofenic acid is structurally represented as shown below

Pharmaceutical compositions comprising Tiaprofenic acid or a pharmaceutically acceptable salt and process for the preparation thereof was disclosed in US 4,159,986, wherein carbon tetrachloride is used for recrystallization to get crystalline Tiaprofenic acid. Though carbon tetrachloride is a class I solvent, it is highly toxic and environmentally hazardous. Hence its usage in pharmaceuticals is restricted. According to the ICH guidelines, the recommended limit of carbon tetrachloride usage should not be above 4 ppm. This limit is difficult to achieve at the industrial scale due to the little stability of the product. According to ICH standards carbon tetrachloride is under the class of solvents that should be avoided in pharmaceutical products.

The present invention relates to process for the preparation of Tiaprofenic acid in its polymorphic form wherein different organic solvents are used in place of carbontetrachloride.

Object of the invention:

The main object of the present invention is to provide novel polymorphic form of Tiaprofenic acid.

Another object of the present invention is to provide novel process for the preparation of crystalline Tiaprofenic acid.

Summary of the invention:

The main aspect of the present invention provides a polymorphic form of Tiaprofenic
acid.

Another aspect of the present invention provides a crystalline polymorphic form of

Tiaprofenic acid which is characterized by PXRD peaks at 10.1, 15.1, 15.5, 21.8, 23.1,
25.0, 31.3±0.2 29 values

Yet another aspect of the present invention provides a crystalline polymorphic form of
Tiaprofenic acid which is characterized by DSC having a single melting point 87.50°C

Yet another aspect of the present invention provides a crystalline Tiaprofenic acid which
is characterized by FTIR having characteristic absorption bands at 1702 cm"1, 1625 cm"1.

Yet another aspect of the present invention provides a process for the preparation of
crystalline polymorphic form of Tiaprofenic acid comprising the steps of:

a) dissolving Tiaprofenic acid in an organic solvent,
b) heating the reaction mixture,
c) optionally cooling the reaction mixture, and
d) isolating crystalline Tiaprofenic acid

Brief description of the drawings:

Fig 1 is the XRD pattern of crystalline Tiaprofenic acid

Fig 2 is the DSC of crystalline Tiaprofenic acid heating at 10° C./min.

Fig 3 is the FTIR of crystalline Tiaprofenic acid

Powder X-ray Diffraction (PXRD)

The PXRD measurements were carried out using PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of 0/0 configuration and X'Celerator detector. The Cu- anode X-ray tube is operated at 40kV and 30mA. The experiments were conducted over the 20 range of 2.0°-50.0°, 0.030° step size and 50 seconds step time.

Differential Scanning Calorimetry (DSC)

The DSC measurements were carried out using the instrument DSC Q1000 of TA instruments. The experiments were performed at a heating rate of 10.0°C/minute over a temperature range of 30°C-300°C purging with nitrogen at a flow rate of 50ml/minute.

Detailed description of the invention:

The present invention relates to crystalline polymorphic form of Tiaprofenic acid. The invention further relates to process for the preparation of crystalline polymorphic form of Tiaprofenic acid.

In one embodiment, the present invention relates to polymorphic form of Tiaprofenic acid characterized by powder X-ray diffraction pattern with peaks at 7.34±0.2, 10.11±0.2, 10.79±0.2, 15.17±0.2, 15.5±0.2, 17.28±0.2, 21.84±0.2, 23.16±0.2, 25.06±0.2, 31.38±0.2 20 values.

In another embodiment, the present invention relates to polymorphic form of Tiaprofenic acid as shown in figure 1.

In yet another embodiment, the present invention relates to crystalline polymorphic form of Tiaprofenic acid further characterized by the DSC as shown in figure 2 with a endothermic peak at about 87.50 °C.

In yet another embodiment, the present invention relates to crystalline polymorphic form of Tiaprofenic acid further characterized by FT-IR as shown in figure 3. In yet another embodiment, the present invention relates to process for the preparation of crystalline polymorphic form of Tiaprofenic acid comprising the steps of:

a) dissolving Tiaprofenic acid in an organic solvent,
b) heating the reaction mass,
c) optionally cooling the reaction mass, and
d) isolating crystalline Tiaprofenic acid

According to the present invention dissolving Tiaprofenic acid in an organic solvent selected from toluene, dichloromethane or cyclohexane, heating the reaction mass for dissolution, cooling the reaction mass to afford novel crystalline Tiaprofenic acid.

The following non-limiting examples illustrate specific embodiments of the present invention. They should not construe it as limiting the scope of present invention in any way.

Examples:
Example 1

Tiaprofenic acid (25 gms) was dissolved in toluene at 25-35°C and stirred for 15 minutes. The reaction mixture was heated to 45-50°C. After dissolution, stirred the reaction mass for 30min, followed by cooling to 25-30 °C, further cooled to 0-5 °C. Filtered the mass and washed with chilled toluene. The obtained cake was dried at 40-50°C.

Example 2
Tiaprofenic acid (25 gms) was dissolved in methylene chloride at 25-35°C and stirred for 15 minutes. The reaction mixture was heated to 45-50°C. After dissolution, stirred the reaction mass for 30min, followed by cooling to 25-30 °C, further cooled to 0-5 °C. Filtered the mass and washed with chilled methylene chloride. The obtained cake was dried at 40-50°C.

Claims:

1. A process for preparing crystalline Tioprofenic acid comprising the steps of:

a) dissolving Tioprofenic acid in an organic solvent,
b) heating the reaction mixture,
c) optionally cooling the reaction mixture, and
d) isolating crystalline Tioprofenic acid.

2. The process according claim 1, wherein the solvent is selected from toluene, dichloromethane or cyclohexane

3. Crystalline Tiaprofenic acid characterized by an X-ray powder diffraction pattern having peaks at about 10.1, 15.1, 15.5, 21.8, 23.1, 25.0, 31.3 ± 0.2 20 values.

4. Crystalline Tiaprofenic acid as shown in figure 1.

5. The crystalline Tiaprofenic acid according to claim 3, is characterized by a differential scanning calorimeter (DSC) having a single melting point at 87.50°C.

6. The crystalline Tiaprofenic acid according to claim 3, is characterized by FTIR having characteristic absorption bands at 1702 cm-1, 1625 cm-1