Solid dispersion of amorphous ribociclib or pharmaceutically acceptable salt thereof and pharmaceutical adjuvant, and preparation method thereof

Abstract

The invention provides a solid dispersion of amorphous ribociclib or a pharmaceutically acceptable salt thereof and a pharmaceutical adjuvant, and a preparation method thereof. The solid dispersion contains ribociclib or the pharmaceutically acceptable salt thereof and the pharmaceutical adjuvant, wherein a weight ratio of ribociclib or the pharmaceutically acceptable salt thereof to the pharmaceutical adjuvant is 1: (0.1-100), ribociclib or the pharmaceutically acceptable salt thereof is amorphous, and the X-ray powder diffraction spectrum of the solid dispersion does not contain the characteristic peaks of crystals of ribociclib or the pharmaceutically acceptable salt thereof after deduction of the background peaks of the pharmaceutical adjuvant. The solid dispersion of ribociclib or thepharmaceutically acceptable salt thereof and the pharmaceutical adjuvant has good stability and dispersibility; the dissolution rate of ribociclib or the pharmaceutically acceptable salt thereof is improved; the bioavailability of the solid dispersion and body absorption of ribociclib are improved; and under accelerated test conditions, the solid dispersion can maintain good physical stability and chemical stability. The preparation method for the amorphous solid dispersion of the invention has the advantages of simple operation, low cost, good reproducibility, easy realization and suitability for industrial production.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a solid dispersion of amorphous ribocicillin or a pharmaceutically acceptable salt thereof and pharmaceutical auxiliary materials and a preparation method thereof. Background technique

[0002] Riboxilin, the English name is Ribociclib, the chemical name is 4-(5-chloro-3-isopropyl-1H-pyrazol-4-yl)-N-(5-(4-(dimethylamino)piper Pyridin-1-yl)pyridin-2-yl)pyrimidin-2-amine, a cyclin-dependent kinase 4 / 6 inhibitor developed by Novartis, Switzerland, for the treatment of advanced breast cancer in postmenopausal women. The structure of this medicine is as shown in formula (I):

[0003]

[0004] In October 2016, the U.S. Food and Drug Administration (FDA) said in October 2016 that it would expedite the review of Novartis' blockbuster drug ribocicillin, while the European Medicines Agency (EMA) also began reviewing the drug. Riboxiclin combined with the aromatas...

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