Olaparib dissolution enhancing composition

Abstract

The invention relates to an olaparib dissolution enhancing composition, a preparation method and application thereof, as well as a medicine containing the olaparib dissolution enhancing composition. The olaparib dissolution enhancing composition is prepared from the following components: olaparib, copovidone and a dissolution accelerator, wherein based on 100 parts by weight of olaparib, the copovidone is more than 100 parts by weight and less than 200 parts by weight, and the dissolution accelerator is 20-150 parts by weight. The olaparib dissolution enhancing composition and the medicine prepared from the olaparib dissolution enhancing composition have controllable stability, can be used for improving oral absorption of active ingredients, and can improve the medication convenience of patients since auxiliary dosage is reduced so as to facilitate industrial production.

Description

technical field [0001] The invention belongs to the technical field of olaparib preparations, and in particular, relates to a composition for enhancing the dissolution of olaparib, its preparation method and its use in the preparation of drugs for preventing or treating tumors, and the composition containing said olaparib A drug in a dissolution-enhancing composition. Background technique [0002] With the World Health Organization discussing tumor as a chronic disease that can be controlled and cured, in recent years, the concept of tumor treatment has changed from the traditional "survival without tumor" to "survival with tumor". Transition to Survival and Quality of Life. "Survival with tumor" significantly prolongs the survival period of patients compared with traditional chemotherapy (~5-10 years VS~1 year), and this "chronic treatment" method promotes the transformation of patients' medication from injection to oral administration, which is convenient for long-term us...

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Problems solved by technology

[0008] 1) A kind of olaparib solid dispersion preparation is disclosed in WO2010041051 and CN102248945B. The olaparib solid dispersion of this invention is prepared with copovidone as the main material. The weight ratio of olaparib and copovidone is It is 1:2 to 1:4, and the proportion of the active agent is 20% to 30%. Since copovidone is difficult to dissolve after being pulverized and pressed into tablets, it needs to add 14.7% by weight of mannitol to dissolve effectively, and the amount of excipients is large. Difficulty swallowing for advanced cancer patients limits development of high-dose formulations

[0009] 2) CN104434809B discloses a solid dispersion of olaparib, the solid dispersion of olaparib of this invention is prepared with povidone as the main material, and the ratio range of olaparib and polymer is 25-100 parts Olaparib, 50-250 parts of povidone, the preparation of tablet needs to add disintegrant and a large amount of diluent, the amount of auxiliary material is large, and povidone has poor thermal stability when prepared by melt extrusion method, easy to Disadvantages of degradation and blackening

[0010] 3) EP3263095 discloses a solid dispersion preparation of olaparib. The solid dispersion of this invention is prepared from a hydrophilic polymer with a glass transition temperature of 40-100°C. The composition of olaparib and the polymer The ratio ranges from 1:0.5 to 1:5, the preferred range is 1:1 to 1:3, specifically the Soluplus and Eudragit series, which use polymers with low glass transition temperatures, and the risk of drug crystallization during storage is high , after 10 days of standing at 40°C and 75% RH in its various examples (EudragitE1001:1, 1:3), endothermic peaks appear in DSC, and the stability of solid dispersions is poor

[0011] 4) CN106692066A discloses a preparation method of olaparib solid dispersion and its product. This invention prepares solid dispersion by melt extrusion, and the polymers used are povidone K30 and copovidone, Austrian Lapani weight percentage is 5%-30%, polymer weight percentage is 70%-95%, there is the shortcoming that polymer dosage ratio is high and povidone is not suitable for high temperature (200 ℃) extruding

[0012] The above patent search results show that the existing olaparib solid dispersion preparations need to use a large number of excipients to improve the bioavailability of the drug, and patients have problems with the convenience of administration when large doses are administered; the amount of excipients used is small or the glass transition temperature is low. Solid dispersions made from polymers with limited stability or solubilization

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