A new crystal form X of olaparib and its preparation method
A crystal form and seed crystal technology, which is applied in the new crystal form X of olaparib and its preparation field, can solve the problems of high melting point and unfavorable hot-melt extrusion process production, and achieve drug efficacy improvement, excellent stability and Low melting point performance and good product stability
Active Publication Date: 2022-03-25
SCINOPHARM CHANGSHU PHARMA
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Problems solved by technology
[0007] For solid preparations of crystalline drugs, the stability and melting point of the preparation have a lot to do with the crystal form of the bulk drug. The olaparib crystal form disclosed in the prior art has good stability, but the melting point is generally Higher, generally above 200°C, which is not conducive to the production of hot-melt extrusion technology; therefore, it is urgent to develop a new crystal form with good stability and low melting point that is convenient for the preparation of solid preparations by hot-melt extrusion technology, and improve production efficiency
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[0030] A method for preparing a new crystal form X of olaparib, comprising the steps of:
[0031] (1) adding the crude product of olaparib and an organic solvent into the reaction flask, raising the temperature to reflux, filtering the reaction solution after clarification, to obtain the olaparib solution;
[0032] Wherein the purity of the crude product of olaparib is not less than 98%, and the organic solvent is C 1 -C 4 One or more alcohols, ethanol is used in this embodiment.
[0033] (2) Add the olaparib solution dropwise to a container containing anti-solvent water, and naturally cool to room temperature to crystallize after the dropwise addition to form a suspension containing olaparib;
[0034] (3) After stirring for 2-4 hours, the suspension was cooled, separated and filtered, and then dried under reduced pressure to obtain olaparib crystal form III solid, wherein: the temperature of reduced-pressure drying was controlled at 40-70°C. After stirring for 3 hours, the...
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Abstract
The present invention discloses a new crystal form X of olaparib, whose X-ray powder diffraction pattern has 2theta values of 7.129±0.5, 10.352±0.5, 12.045±0.5, 15.353±0.5, 20.930±0.5, 21.054±0.521. There are characteristic peaks at 234±0.5, 21.365±0.5 and 27.115±0.5. The present invention also provides a preparation method corresponding to the new crystal form X of olaparib. Through the above method, the product obtained by the present invention has a smaller melting point, which is beneficial to The production of the hot-melt extrusion preparation can improve the drug efficacy of the product. At the same time, the preparation method is simple and easy to produce. The obtained new solid form can be stored for a long time and has good stability.
Description
technical field [0001] The invention relates to the technical field of chemistry and medicine, in particular to a new crystal form X of olaparib and a preparation method thereof. Background technique [0002] Olaparib (Olaparib), chemical name 4-(3-{[4(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}4-fluorophenyl)phthalazin-1(2H)-one, is An organic compound with the chemical formula C 24 h 23 FN 4 o 3 , white powder, the structural formula is as follows: [0003] [0004] Olaparib is a small molecule, potent oral PARP inhibitor developed by KuDOS Pharmaceuticals, a wholly-owned subsidiary of AstraZeneca, which promotes tumor cell apoptosis by inhibiting DNA damage repair in tumor cells. Death, which can enhance the efficacy of radiotherapy and chemotherapy with alkylating agents and platinum drugs. [0005] There are many published patents about olaparib, such as: US Patent No. 7,692,006 discloses the preparation of 4-(3-{[4(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}...
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IPC IPC(8): C07D237/32
CPCC07D237/32C07B2200/13
Inventor 秦健雄韦秀琼
Owner SCINOPHARM CHANGSHU PHARMA