Crystalline form of Ribociclib succinate
The present invention provides a novel crystalline form of Ribociclib succinate, Ribociclib succinate Form APO-I, including Ribociclib succinate, benzyl alcohol and water, compositions thereof, processes for the preparation thereof, and the use of this crystalline form in the treatment of conditions associated with increased CDK4/6 kinase activity, and in particular, cancers, including certain forms of breast cancer.
1. A crystalline form of Ribociclib succinate comprising Ribociclib succinate, benzyl alcohol and water that is characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.4°, 11.1° and 15.1°, and at least three further peaks selected from the group consisting of: 5.0°, 7.5°, 13.9°, 14.5°, 17.4°, 18.9°, 20.5°, 21.2°, 22.1° and 23.7°.
2. The crystalline form of claim 1 , that is characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 5.0°, 6.4°, 7.5°, 11.1°, 13.9°, 14.5°, 15.1° 17.4°, 18.9°, 20.5°, 21.2°, 22.1° and 23.7°.
3. A pharmaceutical composition comprising the crystalline form of Ribociclib succinate according to claim 1 , and one or more pharmaceutically acceptable excipients.
4. The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition is a tablet.
5. A process for the preparation of the crystalline form of Ribociclib succinate according to claim 1 , comprising treating a solution comprising Ribociclib succinate or Ribociclib and succinic acid, benzyl alcohol and water with a C3-C6 alkyl ester.
6. The process of claim 5 , wherein the C3-C6 alkyl ester is selected from the group consisting of methyl acetate, ethyl acetate, isopropyl acetate, isobutyl acetate and n-butyl acetate.
7. The process of claim 6 , wherein the C3-C6 alkyl ester is n-butyl acetate.
8. The process of claim 7 , wherein the molar ratio of Ribociclib succinate or Ribociclib to benzyl alcohol used in the process is between approximately 1:35 and approximately 1:55.
9. The process of claim 8 , wherein the molar ratio of Ribociclib succinate or Ribociclib to water used in the process is between approximately 1:10 and approximately 1:20.
10. The crystalline form of claim 1 , wherein the molar ratio of Ribociclib to benzyl alcohol to water is approximately 1:1:1.
11. The crystalline form of claim 1 , characterized by a weight loss as determined by thermal gravimetric analysis of between about 2% and about 3% in the temperature range of about 40° C. to about 90° C.