NOVEL CRYSTALLINE POLYMORPHIC FORM OF A CAMPTOTHECIN ANALOGUE

• US 20070105885A1
• Filed: 10/10/2006
• Published: 05/10/2007
• Est. Priority Date: 10/10/2005
• Status: Active Grant

• Current Assignee: Cipla (EU) Limited
• Original Assignee: Cipla (EU) Limited
• Inventors: Gangrade, Manish, Kanathala, Shashi, Kankan, Rajendra, Pathi, Srinivas, Rao, Dharmaraj
• Granted Patent: US 8,349,863 B2
• Time in Patent Office: Days
• US Class Current: 514/283
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings

Abstract

The invention relates to a novel crystalline form of topotecan hydrochloride, and methods of making the same. The characteristic XRPD pattern and FT-IT patterns are shown in FIGS. 1 and 2.

Claims

1. A crystalline form A of topotecan hydrochloride having an XRPD pattern with peaks at 6.08, 6.94, 8.10, 9.96, 10.16, 11.68, 12.28, 13.08, 13.62, 14.32, 15.44, 16.46, 16.56, 17.58, 18.42, 19.32;

20.14, 21.22, 21.88, 22.54, 22.72, 23.38, 24.14, 24.36, 24.78, 25.02, 25.50, 26.42, 26.86, 27.18, 27.44, 28.10, 28.76, 29.42, 29.68 and 30.02°

2θ

(±

0.2°

).

3. A crystalline form A of topotecan hydrochloride according to claim 1, wherein the Topotecan hydrochloride has a water content in the range of about 10 to 12 wt %.

8. A crystalline form A of topotecan hydrochloride according to claim 1 comprising (4S)-topotecan hydrochloride.

20. A pharmaceutical formulation comprising a crystalline form A of topotecan hydrochloride of claim 1 in combination with a pharmaceutically acceptable carrier.

21. A method of treating a tumour comprising administering a therapeutically effective amount of a crystalline form A of topotecan hydrochloride of claim 1 to a patient in need thereof.

2. A crystalline form A of topotecan hydrochloride having characteristic FT-IR peaks at 1743, 1656, 1596, 1560 and 1507 cm⁻

1.

4. A crystalline form A of topotecan hydrochloride according to claim 2, wherein the Topotecan hydrochloride has a water content in the range of about 10 to 12 wt %.

9. A crystalline form A of topotecan hydrochloride according to claim 2 comprising (4S)-topotecan hydrochloride.

5. A crystalline form A of topotecan hydrochloride having an XRPD pattern as shown in FIG. 1.

10. A crystalline form A of topotecan hydrochloride according to claim 5 comprising (4S)-topotecan hydrochloride.

6. A crystalline form A of topotecan hydrochloride having an FT-IR spectrum as shown in FIG. 2.

11. A crystalline form A of topotecan hydrochloride according to claim 6 comprising (4S)-topotecan hydrochloride.

7. A crystalline form A of topotecan hydrochloride having a water content in the range of about 10 to 12 wt %.

12. A process for preparing crystalline form A of topotecan hydrochloride, comprising:

suspending topotecan hydrochloride in methanol;

stirring at a temperature ranging from 25 to 30°

C.;

cooling the reaction mass to −

10 to 25°

C.; and

recovering the topotecan hydrochloride form A by filtration and drying.

13. A process according to claim 12, wherein the reaction mass is cooled to a temperature ranging from 10 to 15°

C.

14. A process according to claim 12, wherein the reaction mass is stirred during said cooling step.

15. A crystalline form A of topotecan hydrochloride obtaining by a process according to claim 12.

19. A crystalline form A of topotecan hydrochloride obtaining by a process according to claim 12.

16. A process for preparing crystalline form A of topotecan hydrochloride, comprises suspending topotecan base in methanol;

adding aqueous HCl and stirring at 25-30°

C.;

cooling the reaction mass to a temperature ranging from −

10 to 25°

C.; and

recovering the topotecan hydrochloride form A by filtration and drying.

17. A process according to claim 16, wherein the reaction mass is cooled to a temperature ranging from 10 to 15°

C.

18. A process according to claim 16, wherein the reaction mass is stirred during said cooling step.