A crystal form of ribociclib monosuccinate

Abstract

The present invention relates to a crystal form of Ribociclib monosuccinate, whose X-ray powder diffraction pattern at 25°C has a 2theta value of 9.0°±0.2°, 9.5°±0.2°, 11.5±0.2°, 12.9±0.2°, 13.9±0.2°, 15.1±0.2°, 15.8±0.2°, 17.7±0.2°, 18.3±0.2°, 19.0±0.2°, 20.5±0.2°, 21.9±0.2°, 23.0±0.2°, 23.9±0.2°, 24.9±0.2°, 25.9±0.2°, 27.9±0.2°, 29.2±0.2°, 29.9±0.2°, 30.5±0.2°, 32.0±0.2°, 33.7±0.2°, 36.2±0.2°, There are characteristic peaks at 37.4±0.2°, 37.7±0.2°, 39.5±0.2°, 41.0±0.2°, 41.6±0.2°, 44.0±0.2°. The crystal form I provided by the invention has low hygroscopicity, simplifies the preparation and post-treatment process of medicines, and is easy for industrial production. Compared with the existing crystal forms, the crystal form I has better stability, and it is not easy to turn crystals during storage, so as to avoid changes in bioavailability and drug efficacy. At the same time, it has better powder properties and has a strong Economic Value.

Description

technical field [0001] The invention relates to a crystal form of ribociclib monosuccinate. Background technique [0002] Cyclin-dependent kinase 4 / 6 (cyclin-dependent kinase4 / 6, CDK4 / 6) is a kind of serine / threonine kinase, which binds to cyclin D (cyclinD) and regulates the transition of cells from G1 phase to S phase. Abnormalities of the "cyclinD-CDK4 / 6-INK4-Rb pathway" exist in many tumors. The change of this pathway accelerates the process of G1 phase, which accelerates the proliferation of tumor cells and obtains a survival advantage. Therefore, interfering with it has become a therapeutic strategy, and CDK4 / 6 has therefore become one of the anti-tumor targets. [0003] LEE011 is a small molecule inhibitor of cyclin-dependent kinase 4 / 6, developed by Novartis Pharmaceuticals for the treatment of drug-resistant breast cancer and melanoma drug Ribociclib, officially approved for marketing on March 17, 2017, The trade name is Kisqali. The active ingredient of ribocicl...

AI Technical Summary

Problems solved by technology

The solubility of the hydrate form is lower, less than 0.5mg / mL, and the solubility of the non-hydrate form is better. Therefore, we choose the non-hydrate form as the comparison crystal form, but the non-hydrate form can be dissolved in isopropanol at 80±3℃. Medium reaction crystallization, high temperature increases the risk of esterification reaction between succinic acid and isopropanol, and also increases the risk of degradation

In addition, the non-hydrated form is easy to crystallize. Under 90% RH, up to 7.35% of the non-hydrated form will be converted into a hydrated form. The transformation of the crystal form of the drug will bring problems such as efficacy and safety to the drug.

In addition, the non-hydrated powder has poor physical properties. These unfavorable properties may reduce the production efficiency of tableting and filling in the preparation, and at the same time bring greater difficulties to the quality control of the drug.

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