DESC:CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of earlier Indian provisional patent application No. Provisional Patent Application Nos. 201841015613 filed on April 25, 2018 which is incorporated by reference herein in its entirety. All literature and patent references cited in this specification are likewise incorporated herein by reference in their entirety.
FIELD OF THE INVENTION
The present invention provides polymorphic forms of Rucaparib (S)-camsylate and Rucaparib free base.
BACKGROUND OF THE INVENTION
Rucaparib is an inhibitor of the mammalian polyadenosine 5’-diphosphoribose polymerase (PARP) enzyme. The chemical name is 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt, which is represented by the following structural formula.

Rucaparib is marketed under the brand name RUBRACA by Clovis Oncology.
Rucaparib is first reported in US 6495541. Rucaparib Camsylate salt and polymorphs are reported in US 9045487 and US 8754072.
OBJECT AND SUMMARY OF THE INVENTION
The principal aspect of the present invention is to provide crystalline forms of Rucaparib (S)-Camsylate, Rucaparib free base and processes for the preparation of the same.
In one aspect, present invention provides crystalline Form M1 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) dissolving Rucaparib in 18-22 volumes of solvent;
b) adding (S)-camphor sulfonic acid solution; and
c) isolating crystalline Rucaparib (S)-Camsylate Form M1.
In another aspect, present invention provides crystalline Form M1 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) dissolving Rucaparib in a solvent;
b) seeding with Rucaparib (S)-camsylate Form M1;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M1.
In one more aspect, present invention provides crystalline Form M2 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) suspending Rucaparib in a solvent or mixtures thereof;
b) optionally seeding with Rucaparib (S)-Camsylate Form M2;
c) adding (S)-camphor sulfonic acid solution; and
e) isolating crystalline Rucaparib (S)-Camsylate Form M2.
In another aspect, present invention provides crystalline Form M3 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) dissolving Rucaparib in 13-17 volumes of solvent;
b) adding (S)-camphor sulfonic acid solution; and
c) isolating crystalline Rucaparib (S)-Camsylate Form M3.
In another aspect, present invention provides crystalline Form M3 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) dissolving Rucaparib in a solvent;
b) seeding with Rucaparib (S)-camsylate Form M3;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M3.
In one aspect, present invention provides crystalline Form M1 of Rucaparib and process for the preparation of the same.
a) suspending Rucaparib (S)-camsylate in an aqueous base and alcohol solvent; and
b) drying at 45-55 °C to isolate crystalline Rucaparib Form M1.
In one aspect, present invention provides Crystalline Form M2 of Rucaparib.
In one more aspect, present invention provides crystalline Form M3 of Rucaparib and process for the preparation of the same.
a) suspending Rucaparib (S)-camsylate in an aqueous base and alcohol solvent; and
b) drying at 60-70 °C to isolate crystalline Rucaparib Form M3;
In one aspect, present invention provides crystalline Form M4 of Rucaparib and process for the preparation of the same.
a) suspending Rucaparib Form M3 in a ketone solvent; and
b) isolating crystalline Rucaparib Form M4.
In one aspect, present invention provides crystalline Form M5 of Rucaparib and process for the preparation of the same.
a) drying Rucaparib Form M2; and
b) isolating crystalline Rucaparib Form M5.
BRIEF DESCRIPTION OF THE DRAWINGS
Further aspects of the present disclosure together with additional features contributing thereto and advantages accruing therefrom will be apparent from the following description of embodiments of the disclosure which are shown in the accompanying figures wherein:
Figure 1: PXRD pattern of crystalline Form M1 of Rucaparib (S)-camsylate;
Figure 2: PXRD pattern of crystalline Form M2 of Rucaparib (S)-camsylate
Figure 3: PXRD pattern of crystalline Form M3 of Rucaparib (S)-camsylate
Figure 4: PXRD pattern of crystalline Form M1 of Rucaparib.
Figure 5: PXRD pattern of crystalline Form M2 of Rucaparib.
Figure 6: PXRD pattern of crystalline Form M3 of Rucaparib.
Figure 7: PXRD pattern of crystalline Form M4 of Rucaparib.
Figure 8: PXRD pattern of crystalline Form M5 of Rucaparib.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides crystalline forms of Rucaparib (S)-Camsylate; Rucaparib free base and processes for the preparation of the same.
Instrumentation Details:
The PXRD measurements were carried out using BRUKER D8 Discover powder diffractometer equipped with goniometer of ?/2? configuration and Lynx Eye detector. The Cu-anode X-ray tube was operated at 40kV and 40mA. The experiments were conducted over the 2? range of 2.0°-50.0°, 0.030° step size and 0.2 seconds step time.
One embodiment of the present invention provides crystalline Form M1 of Rucaparib (S)-camsylate.
Within the context of the present invention, crystalline Form M1 of Rucaparib (S)-camsylate disclosed herein may be characterized by PXRD pattern having peaks 11.89, 12.90, 15.34, 16.33, 17.87, 20.0, 21.95, 24.94 and 30.0±0.2° 2?.
In another embodiment, present invention provides crystalline Form M1 of Rucaparib (S)-camsylate characterized by PXRD pattern substantially as depicted in FIG. 1
In one aspect, present invention provides crystalline Form M1 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) dissolving Rucaparib in 18-22 volumes of solvent;
b) adding (S)-camphor sulfonic acid solution; and
c) isolating crystalline Rucaparib (S)-Camsylate Form M1.
As per the above embodiment, Rucaparib is dissolved in 18-22 volumes of a solvent to give clear solution of Rucaparib. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; more preferably ethanol.
To the resulting Rucaparib solution is added camphor sulphonic acid solution. The solution of camphor sulfonic acid may prepare by dissolving camphor sulfonic acid in a solvent. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; more preferably ethanol.
Next, the solution of Rucaparib and Camphor sulphonic acid is heated to 70-90 °C; preferably at 75-85 °C. The reaction mixture further cooled and filtered to isolate crystalline Rucaparib (S)-Camsylate.
In another embodiment, the above obtained crystalline Rucaparib (S)-Camsylate is dried at 40-60 °C, preferably 45-55 °C for 2-5 h to isolate crystalline Rucaparib (S)-Camsylate Form M1.
In another embodiment of the present invention provides a process for the preparation of Form M1 of Rucaparib (S)-camsylate comprising:
a) dissolving Rucaparib in a solvent;
b) seeding with Rucaparib (S)-camsylate Form M1;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M1.
As per the above embodiment, Rucaparib is dissolved in solvent to give clear solution. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; more preferably ethanol.
To the resulting Rucaparib solution is added camphor sulphonic acid solution. The solution of Camphor sulfonic acid may prepare by dissolving camphor sulfonic acid in a solvent. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; more preferably ethanol.
Next, the solution of Rucaparib and Camphor sulphonic acid is heated to 70-90°C; preferably at 75-85°C. The reaction mixture further cooled and filtered to isolate crystalline Rucaparib (S)-Camsylate.
In another embodiment, the above obtained crystalline Rucaparib (S)-Camsylate is dried at 40-60 °C, preferably 45-55°C for 2-5 h to isolate crystalline Rucaparib (S)-Camsylate Form M1.
One more embodiment of the present invention provides crystalline Form M2 of Rucaparib (S)-camsylate.
Within the context of the present invention, crystalline Form M2 of Rucaparib (S)-camsylate disclosed herein may be characterized by PXRD pattern having peaks 13.49, 17.99, 20.47, 22.09, 23.46, 24.06 and 27.79±0.2° 2?.
In another embodiment, present invention provides crystalline Form M2 of Rucaparib Camsylate characterized by PXRD pattern substantially as depicted in FIG. 2
Another embodiment of the present invention provides a process for the preparation of Form M2 of Rucaparib (S)-camsylate comprising:
a) suspending Rucaparib in suitable solvent or mixture thereof;
b) optionally seeding with Rucaparib (S)-camsylate Form M2;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M2.
As per the above embodiment, Rucaparib is suspended in a suitable solvent or mixtures thereof and heated to give clear solution of Rucaparib. The suitable solvent or mixtures thereof are selected from tetralin, 2-methyl-2-butanol, methanol, ethanol, isopropyl alcohol, n-propanol, n-butanol, 2-butanol; preferably mixture of tetralin and 2-methyl-2-butanol.
In one embodiment, Rucaparib may be suspended in tetralin.
In another embodiment Rucaparib may be suspended in 2-methyl-2-butanol.
Within the context, Rucaparib suspension may be optionally seeded with crystalline Rucaparib (S)-camsylate Form M2.
The resulting Rucaparib suspension is heated to 60-80 °C; preferably 65-75 °C. To the resulting Rucaparib solution is added camphor sulphonic acid solution. The solution of Camphor sulfonic acid may prepare by dissolving camphor sulfonic acid in a solvent. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; more preferably 2-methyl-2-butanol.
Next, the solution of Rucaparib and Camphor sulphonic acid is heated to 60-80 °C; preferably 65-75 °C. The reaction mixture further cooled and filtered to isolate crystalline Rucaparib (S)-Camsylate.
In another embodiment, the above obtained crystalline Rucaparib (S)-Camsylate may be dried at 40-60 °C, preferably 45-55 °C for 2-5 h to isolate crystalline Rucaparib (S)-Camsylate Form M2.
In an additional embodiment, isolated crystalline Rucaparib (S)-Camsylate may be dried for 10-15 h, preferably 10-12 h to isolate crystalline Rucaparib (S)-Camsylate Form M2.
Another embodiment of the present invention provides crystalline Form M3 of Rucaparib (S)-camsylate.
Within the context of the present invention, crystalline Form M3 of Rucaparib (S)-camsylate disclosed herein may be characterized by PXRD pattern having peaks 13.31, 15.70, 20.29, 20.80, 23.36, 23.82, 24.74, and 26.24±0.2° 2?.
In another embodiment, present invention provides crystalline Form M3 of Rucaparib (S)-camsylate is characterized by PXRD pattern substantially as depicted in FIG. 3
In another aspect, present invention provides crystalline Form M3 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) dissolving Rucaparib in 13-17 volumes of solvent;
b) adding (S)-camphor sulfonic acid solution; and
c) isolating crystalline Rucaparib (S)-Camsylate Form M3.
As per the above embodiment, Rucaparib is dissolved in 13-17 volumes of solvent to give clear solution. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n- propanol, n-butanol, 2-butanol, isopropyl alcohol, 2-methyl-2-butanol; more preferably ethanol.
To the resulting Rucaparib solution added camphor sulphonic acid solution. The solution of Camphor sulfonic acid may prepare by dissolving camphor sulfonic acid in a solvent. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol and isopropyl alcohol.
Next, the solution of Rucaparib and Camphor sulphonic acid is heated to 70-90 °C; preferably at 75-85°C. The reaction mixture further cooled and filtered to isolate crystalline Rucaparib (S)-Camsylate.
In another embodiment, the isolated crystalline Rucaparib (S)-Camsylate is dried at 40-55 °C for 10-14 h to give crystalline Rucaparib (S)-Camsylate Form M3.
In another embodiment, present invention provides crystalline Form M3 of Rucaparib (S)-camsylate and process for the preparation of the same comprising:
a) dissolving Rucaparib in a solvent;
b) seeding with Rucaparib (S)-camsylate Form M3;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M3.
As per the above embodiment, Rucaparib is dissolved in solvent to give clear solution. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n- propanol, n-butanol, 2-butanol, isopropyl alcohol, 2-methyl-2-butanol; more preferably ethanol.
Within the context, Rucaparib solution may be optionally seeded with crystalline Rucaparib (S)-camsylate Form M3.
To the resulting clear Rucaparib solution is seeded with crystalline Rucaparib (S)-camsylate Form M3 and further added camphor sulphonic acid solution. The solution of Camphor sulfonic acid may prepare by dissolving camphor sulfonic acid in a solvent. The solvent is selected from polar solvents; preferably alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; more preferably ethanol.
Next, the solution of Rucaparib and Camphor sulphonic acid is heated to 70-90°C; preferably at 75-85°C. The reaction mixture further cooled and filtered to isolate crystalline Rucaparib (S)-Camsylate.
In another embodiment, the isolated crystalline Rucaparib (S)-Camsylate is dried at 40-55°C for 10-14 h to give crystalline Rucaparib (S)-Camsylate Form M3.
Another embodiment of the present invention provides crystalline Form M1 of Rucaparib.
Within the context of the present invention, crystalline Form M1 of Rucaparib disclosed herein may be characterized by PXRD pattern having peaks 9.09, 15.19, 22.69, 23.20, 27.72±0.2° 2?.
In another embodiment, present invention provides crystalline Form M1 of Rucaparib characterized by XRPD pattern substantially as depicted in FIG. 4
Another embodiment of the present invention provides a process for the preparation of Form M1 of Rucaparib comprising:
a) suspending Rucaparib (S)-camsylate in an aqueous base and alcohol solvent; and
b) drying at 45-55 °C to isolate crystalline Rucaparib Form M1.
Rucaparib (S)-camsylate is suspended in aqueous base and alcohol solvent. The base selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like; alcohol solvent is selected from methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; preferably methanol.
Further, the above suspension is cooled to 10-20°C. The resulting reaction mass is filtered and dried at 45-55°C preferably at 50 °C to isolate Rucaparib Form M1.
One more embodiment of the present invention provides crystalline Form M2 of Rucaparib.
In one embodiment, crystalline Rucaparib Form M1 is stored at 20-40 °C; preferably at 20-30 °C for about 8-14 days, preferably 9-11 days gives crystalline Rucaparib Form M2.
Within the context of the present invention, crystalline Form M2 of Rucaparib disclosed herein may be characterized by PXRD pattern having peaks 8.48, 18.67, 19.34, 21.80 and 24.24±0.2° 2?.
In another embodiment, present invention provides crystalline Form M2 of Rucaparib characterized by XRPD pattern substantially as depicted in FIG. 5.
In one more embodiment of the present invention provides crystalline Form M3 of Rucaparib.
Within the context of the present invention, crystalline Form M3 of Rucaparib disclosed herein may be characterized by PXRD pattern having peaks 14.69, 22.10, 22.56, and 27.80 ±0.2° 2?.
In another embodiment, present invention provides crystalline Form M3 of Rucaparib characterized by PXRD pattern substantially as depicted in FIG. 6.
Another embodiment of the present invention provides a process for the preparation of Form M3 of Rucaparib comprising:
a) suspending Rucaparib (S)-camsylate in aqueous base and alcohol solvent; and
b) drying at 60-70 °C to isolate crystalline Rucaparib Form M3.
Rucaparib (S)-camsylate is suspended in aqueous base and alcohol solvent. The base selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like; alcohol solvent is selected from methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol, isopropyl alcohol; preferably methanol.
Further, the above suspension is cooled to 10-25°C. The resulting reaction mass is filtered and dried at 60-70°C preferably at 60 °C to isolate Rucaparib Form M3.
In one more embodiment of the present invention provides crystalline Form M4 of Rucaparib.
Within the context of the present invention, crystalline Form M4 of Rucaparib disclosed herein may be characterized by PXRD pattern having peaks 7.79, 13.53, 13.86,14.82, 15.64, 17.017.70,19.87, 20.59, 21.34, 22.50 and 23.35 ±0.2° 2?.
In another embodiment, present invention provides crystalline Form M4 of Rucaparib characterized by PXRD pattern substantially as depicted in FIG. 7.
Another embodiment of the present invention provides a process for the preparation of Form M4 of Rucaparib comprising.
a) suspending Rucaparib Form M3 in a ketone solvent; and
b) isolating crystalline Rucaparib Form M4.
In one embodiment, Rucaparib Form M3 of present invention is dissolved in a ketone solvent such as methyl isobutyl ketone and heated to 35-50°: preferably 40-45°C to and cooled. The resulting reaction mixture is filtered and dried at 40-60°C; preferably 45-50°C to isolate Rucaparib Form M4.
In one more embodiment of the present invention provides crystalline Form M5 of Rucaparib.
Within the context of the present invention, crystalline Form M5 of Rucaparib disclosed herein may be characterized by PXRD pattern having peaks 8.27, 11.66, 14.11, 18.41, 19.06, 21.55, 23.90 and 24.73 ±0.2° 2?.
In another embodiment, present invention provides crystalline Form M5 of Rucaparib characterized by PXRD pattern substantially as depicted in FIG. 8.
Another embodiment of the present invention provides a process for the preparation of Form M5 of Rucaparib comprising.
a) drying Rucaparib Form M2; and
b) isolating crystalline Rucaparib Form M5.
In one embodiment, Rucaparib Form M2 of present invention may be dried at 120-143°C; preferably 125-135 °C to isolate Rucaparib Form M5.
In another embodiment, physical and chemical stability of Rucaparib S-Camsylate crystalline Form M2 and Form M3 samples were determined by storing the samples at 40 °C and 75% relative humidity (RH) and at 25°C and 60% relative humidity (RH) for 3 months. The samples were analyzed by PXRD.

The Rucaparib S-Camsylate Form M2 shows no change in PXRD pattern when stored for 3 months at 40°C and 75% relative humidity (RH) and at 25°C and 60% relative humidity (RH) conditions as mentioned in below Table 1.

The Rucaparib S-Camsylate Form M3 shows no change in PXRD pattern when stored for 3 months at 40°C and 75% relative humidity (RH) and at 25°C and 60% relative humidity (RH) conditions as mentioned in below Table 1.
Table 1
Conditions/ Polymorph Crystalline Form M2 Crystalline Form M3
PXRD PXRD
at 40°C/75% RH
Initial Crystalline Crystalline
1 months Stable Stable
2 months Stable Stable
3 months Stable Stable
at 25°C/60% RH
Initial Crystalline Crystalline
1 months Stable Stable
2 months Stable Stable
3 months Stable Stable

In view of the above description and the examples below, one of ordinary skill in the art will be able to practice the invention as claimed without undue experimentation. The foregoing will be better understood with reference to the following examples that detail certain procedures for the preparation of molecules according to the present invention. All references made to these examples are for the purposes of illustration. The following examples should not be considered exhaustive, but merely illustrative of only a few of the many aspects and embodiments contemplated by the present disclosure.
Examples:
Example 1: Rucaparib S-Camsylate Form M1
0.2 g of Rucaparib Form M2 was dissolved in 4 mL of ethanol at 80±5°C. To the clear solution was added (S)-Camphor sulfonic acid solution [dissolved (S)-camphor sulfonic acid (0.14g) in ethanol (1mL)] slowly at 80±5°C for 5-10 min and maintained under stirring for 3h. The reaction mass was cooled to 25±5°C and further stirred for 12 h. The reaction mass was filtered and dried under vacuum at 50°C for 3h. The product obtained was identified as Rucaparib S-Camsylate Form M1.
Yield: 0.25 g
Example 2: Rucaparib S-Camsylate Form M1
0.5 g of Rucaparib Form M2 was dissolved in 5 mL of ethanol at 80±5 °C. To the clear solution was seeded with 10 mg of Rucaparib S-Camsylate Form M1 at 80±5°C and stirred for 15 min. To the solution was added slowly (S)-Camphor sulfonic acid solution [dissolved (S)-Camphor sulfonic acid (0.36g) in ethanol (1mL)] at 80±5°C for 5-10 min and maintained under stirring for 3 h at 80±5°C. The reaction mass was cooled to 25±5°C and further stirred for 12 h. The reaction mass was filtered and dried under vacuum at 50 °C for 3h. The solid obtained was identified as Rucaparib S-Camsylate form M1.
Yield: 0.6 g
Example 3: Rucaparib S-Camsylate Form M2
0.4 g of Rucaparib Form M3 was suspended in 8 mL of tetralin at 25±5 °C and heated to 70±5°C. To the reaction mass slowly added S-Camphor sulfonic acid solution [dissolved (S)-camphor sulfonic acid (0.29g) in 2-methyl 2-butanol (4mL)] at 70±5°C for 10-15 min and maintained under stirring for 30 min. Then reaction mass was cooled to 25±5°C and further maintained under stirring for 12 h. The reaction mass was filtered and dried under vacuum at 50°C for 3h. The solid obtained was identified as Rucaparib S-Camsylate Form M2.
Yield: 0.4 g
Example 4: Rucaparib S-Camsylate Form M2
0.2 g of Rucaparib Form M3 was suspended in a mixture of 4 mL of 2-methyl 2-butanol and 4 mL of tetralin at 25±5°C and heated to 70±5°C to obtain clear solution. To the reaction solution was slowly added (S)-Camphor sulfonic acid solution [dissolved (S)-camphor sulfonic acid (0.14g) in 2-methyl 2-butanol (2mL)] at 70±5°C for 10-15 min and maintained under stirring for 30 min at 70±5 °C. The reaction mass was further cooled to 25±5 °C, stirred for 12h, filtered and dried under vacuum at 50 °C for 3 h. The solid obtained was identified as Rucaparib S-Camsylate form M2.
Yield: 0.2 g.
Example 5: Rucaparib S-Camsylate Form M2
0.5 g of Rucaparib Form M3 was suspended in 5 mL of 2-methyl 2-butanol at 25±5°C and heated to 80±5°C. To this suspension was seeded with 5 mg of Rucaparib S-Camsylate Form M2. To the reaction mass slowly added S-Camphor sulfonic acid solution [dissolved (S)-camphor sulfonic acid (0.36g) in 2-methyl 2-butanol (5mL)] at 80±5°C for 5-10min and maintained under stirring for 1h. The reaction mass was cooled to 25±5°C and further maintained under stirring for 12h. The reaction mass was filtered and dried under vacuum at 50 °C for 12h. The solid obtained was identified as Rucaparib S-Camsylate Form M2.
Yield: 0.7g
Example 6: Rucaparib S-Camsylate Form M2
4 g of Rucaparib Form M1 was suspended in 100 mL of 2-Methyl-2-Butanol at 25±5°C and heated to 80±5°C. Slowly added (S)-camphor sulfonic acid solution [dissolved (S)-camphor sulfonic acid (2.88g) in 2-methyl 2-butanol (40mL)] at 80±5°C for 10-15min. Stirred the reaction mass for 60 min at 80±5°C, cooled to 25±5°C and further stirred for 15 h at 25±5°C. The reaction mass was filtered, washed with 2-Methyl-2-Butanol and dried under vacuum at 50 °C for 10h. The solid obtained was identified as Rucaparib S-Camsylate Form M2.
Yield: 6.3g
Example 7: Rucaparib S-Camsylate Form M3
0.5 g of Rucaparib Form M2 was dissolved in 7.5 mL of ethanol at 80±5°C to obtain clear solution. To the clear solution was slowly added (S)-Camphor sulfonic acid solution [dissolved (S)-camphor sulfonic acid (0.36g) in ethanol (3mL)] for 5-10min and maintained under stirring for 4h at 80±5°C. The reaction mass was further cooled to 25±5°C, stirred for 12h, filtered and dried under vacuum at 50°C for 12h. The solid obtained was identified as Rucaparib S-Camsylate form M3.
Yield: 0.7g
Example 8: Rucaparib S-Camsylate Form M3
0.5 g of Rucaparib Form M2 was dissolved in 7.5 mL of ethanol at 80±5 °C to obtain clear solution. The clear solution was seeded with 5 mg of Rucaparib S-Camsylate Form M3 seeds. Further, to the reaction mixture was slowly added (S)-Camphor sulfonic acid solution [dissolved (S)-camphor sulfonic acid (0.36g) in ethanol (3mL)] for 5-10 min and maintained under stirring for 4 h at 80±5°C. The reaction mass was further cooled to 25±5°C, stirred for 12 h, filtered and dried under vacuum at 50°C for 12h. The solid obtained was identified as Rucaparib S-Camsylate form M3.
Yield: 0.7g
Example 9: Rucaparib S-Camsylate Form M3
5 g of Rucaparib THF solvate was suspended in 100 mL of 2-methyl-2-butanol at 25±5°C and heated to 80±5°C. The reaction mixture was seeded with 50 mg of Rucaparib S-Camsylate Form M3. Slowly added (S)-camphor sulfonic acid solution (dissolved (S)-camphor sulfonic acid (3.59 g) in 2-methyl 2-butanol (50 mL)) at 80±5°C for 10-15min. The reaction mass was stirred for 60 min at 80±5 °C, cooled to 25±5° C and further stirred for 15 h at 25±5 °C. The reaction mass was filtered, washed with 2-Methyl-2-Butanol and dried under vacuum at 50 °C for 1h. The solid obtained was identified as Rucaparib S-Camsylate Form M3.
Yield: 6.5g; HPLC Purity: 99.56%
Example 10: Rucaparib Form M1
0.43 g of sodium hydroxide dissolved in a mixture of 42 mL of water and 16.5 mL of methanol at 25±5°C and then cooled to 15±5°C, to this was added 3 g of Rucaparib S-Camsylate salt for 10 min. Further, 42 mL of water was added to the reaction suspension and stirred for 1h at 20±5°C. The reaction mass was filtered and dried under vacuum at 50 °C for 2 h. The product obtained was identified as Rucaparib form M1.
Yield: 2.2 g
Example 11: Rucaparib Form M1
1.43 g of sodium hydroxide dissolved in a mixture of 140 mL of water and 55 mL of methanol at 25±5°C and then cooled to 15±5°C, to this was added 10 g of Rucaparib S-Camsylate lot-wise for 10min and maintained under stirring for 90 min at same temperature. 120 mL of water was added to the reaction mixture and stirred for 16 h at 20±5°C. The reaction mass was filtered and dried under vacuum at 50 °C for 16 h. The product obtained was identified as Rucaparib form M1.
Yield: 5.6 g
Example 12: Rucaparib Form M2
Rucaparib Form M1 was stored at 25±5°C in a closed condition for several days and the resulting solid was identified as Rucaparib form M2.
Example 13: Rucaparib Form M3
0.72 g of sodium hydroxide was dissolved in a mixture of 70 mL of water and 27.5 L of methanol at 25±5°C and then cooled to 15±5°C. To this was added 5 g of Rucaparib S-Camsylate lot-wise at 15±5°C for 10 min and maintained under stirring for 2 h at same temperature. 70 mL of water was added and stirred for 15 h at 20±5°C. The reaction mass was filtered and dried under vacuum at 65°C for 12h. The product obtained was identified as Rucaparib form M3.
Yield: 2.7 g
Example 14: Rucaparib Form M4
1 g of Rucaparib Form M3 was suspended in 20 mL of methyl isobutyl ketone at 25±5 °C and heated to 40±5°C and maintained under stirring for 30 min. The reaction mass was cooled to 25±5 °C and stirred for 12 h. The reaction mass was filtered and dried under vacuum at 50 °C for 12 h. The product obtained was identified as Rucaparib form M4.
Yield: 0.7g
Example 15: Rucaparib Form M5
0.2 g of Rucaparib Form M2 was dried at 130 °C under vacuum for 1-2 h. The resulting solid was identified as Rucaparib crystalline Form-M5.

,CLAIMS:1. A crystalline Form M3 of Rucaparib (S)-camsylate characterized by PXRD pattern having peaks 13.31, 15.70, 20.29, 20.80, 23.36, 23.82, 24.74, and 26.24±0.2° 2?.

2. A process for the preparation of crystalline Form M3 of Rucaparib (S)-camsylate comprising:
a) dissolving Rucaparib in 13-17 volumes of solvent;
b) adding (S)-camphor sulfonic acid solution; and
c) isolating crystalline Rucaparib (S)-Camsylate Form M3.

3. A process for the preparation of crystalline Form M3 of Rucaparib (S)-camsylate comprising:
a) dissolving Rucaparib in a solvent;
b) seeding with Rucaparib (S)-camsylate Form M3;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M3.

4. The process as claimed in claim 2 and 3, wherein the solvent is selected from alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol and isopropyl alcohol.

5. A crystalline Form M2 of Rucaparib (S)-camsylate characterized by PXRD pattern having peaks 13.49, 17.99, 20.47, 22.09, 23.46, 24.06 and 27.79±0.2° 2?.

6. A process for the preparation of Form M2 of Rucaparib (S)-camsylate comprising:
a) suspending Rucaparib in suitable solvent or mixture thereof;
b) optionally seeding with Rucaparib (S)-camsylate Form M2;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M2.

7. The process as claimed in claim 6, wherein the solvent is selected from alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol and isopropyl alcohol.

8. A process for the preparation of crystalline Form M1 of Rucaparib (S)-camsylate comprising:
a) dissolving Rucaparib in 18-22 volumes of solvent;
b) adding (S)-camphor sulfonic acid solution; and
c) isolating crystalline Rucaparib (S)-Camsylate Form M1.

9. A process for the preparation of crystalline Form M1 of Rucaparib (S)-camsylate comprising:
a) dissolving Rucaparib in a solvent;
b) seeding with Rucaparib (S)-camsylate Form M1;
c) adding (S)-camphor sulfonic acid solution; and
d) isolating crystalline Rucaparib (S)-Camsylate Form M1.

10. The process as claimed in claim 8 and 9, wherein the solvent is selected from alcoholic solvent such as methanol, ethanol, n-propanol, n-butanol, 2-butanol, 2-methyl-2-butanol and isopropyl alcohol.