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Crystal form, preparing method and application of Olaparib

A technology of crystal forms and mixed crystals, which is applied in organic chemical methods, pill delivery, organic chemistry, etc., can solve the problems of unfavorable olaparib dissolution and large particle size, and achieve improved drug efficacy, simple preparation method, and stable performance. Effect

Inactive Publication Date: 2016-01-20
BEIJING COLLAB PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Olaparib is a poorly soluble drug and is often prepared as a solid preparation for administration. For solid preparations of crystalline drugs, the stability and dissolution rate of the preparation have a great relationship with the crystal form of the raw drug. At present, by Cudos Pharmaceutical Co., Ltd. discloses the crystal form A of olaparib ansolvate in CN101528714B, and its X-ray powder diffraction pattern (2θ) is at 12.0°, 17.8°, 21.1°, 22.3°, 29.2°, 10.5 °, 14.0°, 21.7°, 24.3°, and 26.1°, there are characteristic peaks, and DSC shows that there is an endothermic peak at 210.1°C±1°C. This crystal form has good stability, but its large particle size is not conducive to the development of olaparib. Dissolution in preparation

Method used

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  • Crystal form, preparing method and application of Olaparib
  • Crystal form, preparing method and application of Olaparib
  • Crystal form, preparing method and application of Olaparib

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preparation example Construction

[0037] The present invention also provides a method for preparing the crystalline form of olaparib provided by the present invention, comprising:

[0038] 1) olaparib is mixed with a solvent and refluxed to obtain a olaparib solution,

[0039] The solvent is one or more of n-propanol, isopropanol, n-butanol, isobutanol and tert-butanol;

[0040] 2) Filtrating the olaparib solution and cooling to obtain the olaparib in the crystal form.

[0041]According to the present invention, the present invention mixes olaparib with solvent and refluxes to obtain a saturated solution of olaparib; the solvent is preferably one or more of n-propanol, isopropanol, n-butanol and tert-butanol species; the dosage ratio of the olaparib to the solvent is preferably 1g:(8-20)mL, more preferably 1g:(10-15)mL, most preferably 1g:(12-14)mL.

[0042] The present invention also filters the obtained olaparib solution, cools, and dries to obtain the olaparib of the crystal form; the filtering is prefera...

Embodiment 1

[0052] Add 20.0 g of olaparib (purity 99.1%) and 200 mL of isopropanol into the reaction flask, raise the temperature to reflux, stir for 30 min, and filter while hot. The filtrate is naturally cooled to room temperature for crystallization under stirring, filtered, and depressurized at 50 ° C. After drying, 17.6 g of olaparib with a new crystal form was obtained, with a yield of 88.0% and a purity of 99.9%.

[0053] By performing X-ray powder diffraction on the new crystal form Olaparib prepared in Example 1, the results are shown in figure 1 , figure 1 The X-ray diffraction pattern of the new crystal form olaparib prepared in Example 1 of the present invention;

[0054] By performing differential thermal analysis on the new crystal form olaparib prepared in Example 1, the results are shown in figure 2 , figure 2 The DSC chart of the new crystal form of olaparib was prepared for Example 1 of the present invention.

[0055] The stability of the new crystal form of olapar...

Embodiment 2

[0067] Add 20.0g of olaparib and 300mL of tert-butanol into the reaction flask, raise the temperature to 100°C, stir for 30min, and filter while it is hot. The filtrate is naturally cooled to room temperature for crystallization under stirring, filtered, and dried under reduced pressure at 50°C to obtain 17.9g The new crystal form of olaparib has a yield of 89.5% and a purity of 99.9%.

[0068] X-ray powder diffraction was performed on the obtained crystal form olaparib, and the results showed that the diffraction peak position of olaparib obtained in Example 2 was the same as that in Example 1, and it was the same crystal form.

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Abstract

The invention provides a crystal form, preparing method and application of Olaparib. According to the Olaparib with the new crystal form, CuKa radiation is adopted, powder X-ray diffraction represented by 2 theta angle has diffraction peaks at 22.9+ / -0.5, 23.4+ / -0.5, 21.0+ / -0.5, 17.1+ / -0.5, 17.3+ / -0.5, 14.2+ / -0.5, 15.0+ / -0.5, 13.5+ / -0.5, 18.6+ / -0.5, 20.6+ / -0.5, 10.2+ / -0.5, 20.3+ / -0.5, 21.9+ / -0.5, 25.8+ / -0.5 and 26.5+ / -0.5. The granularity D50 of the Olaparib with the crystal form is 2.45 microns which is quite small, so that dissolving-out speed is high when the Olaparib serves as a preparation, and drug efficacy of a product is improved. Furthermore, the preparing method is simple, and the performance of the obtained Olaparib with the crystal form is stable.

Description

technical field [0001] The present invention relates to the field of crystal forms, in particular to a crystal form of olaparib and a preparation method and application thereof. Background technique [0002] Olaparib, the chemical name is 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one, the English name is Olaparib, and 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, so as to enhance the curative effect of radiotherapy, alkylating agent and platinum drug chemotherapy, mainly used for the treatment of gene mutation cancer of breast cancer gene No. 1 (BRCA-1) and breast cancer gene No. 2 (BRCA-2). Mainly found in breast cancer, ovarian cancer and prostate cancer. [0005] Olaparib is a poorly soluble d...

Claims

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Application Information

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IPC IPC(8): C07D237/32A61K31/502A61P35/00
CPCC07D237/32A61K9/2054C07B2200/13
Inventor 杜立民张宪美谈敦潮方胜邹德超赵大龙王珂
Owner BEIJING COLLAB PHARMA
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