Olaparib and malonic acid eutectic crystal and preparation method thereof

A malonic acid and solvent technology, applied in the field of medicinal chemistry, can solve the problems such as failure to obtain the co-crystal form A of olaparib and urea, low solubility, and limited drug oral absorption efficiency.

Pending Publication Date: 2020-10-27
TIANJIN UNIVERSITY OF TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Olaparib is currently listed as crystal form A, which has low solubility, which limits the oral absorption efficiency of the drug
Patent CN 105753789B discloses the eutectic crystal form A of olaparib and urea, but the inventor repeated the preparation method of the example of patent 105753789B, and failed to obtain the eutectic crystal form of olaparib and urea described in the patent A

Method used

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  • Olaparib and malonic acid eutectic crystal and preparation method thereof
  • Olaparib and malonic acid eutectic crystal and preparation method thereof
  • Olaparib and malonic acid eutectic crystal and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Weigh 900 mg of olaparib and 216 mg of malonic acid, add 15 mL of n-heptane and 250 μL of ethanol to obtain a suspension, stir the suspension at room temperature for 3 h, filter, and dry the obtained white solid at 40 ° C to obtain A solid sample of the cocrystal of lapani and malonic acid in 90.5% yield.

Embodiment 2

[0040] Weigh 60 mg of olaparib and 14.4 mg of malonic acid, add 1 mL of anisole and 10 μL of ethanol to obtain a suspension, stir the suspension at room temperature for 12 h, filter, and dry the obtained white solid at 40 ° C to obtain A solid sample of the cocrystal of olaparib and malonate.

Embodiment 3

[0042] Weigh 60 mg of olaparib and 14.4 mg of malonic acid, add them to a ball mill jar, then add 10 μL of ethyl acetate, grind at a frequency of 20 Hz for 30 min, and dry the resulting white solid at 40 ° C to obtain olaparib and malonic acid Eutectic solid samples.

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Abstract

The invention discloses an olaparib and malonic acid eutectic crystal and a preparation method thereof. In the eutectic crystal, the molar ratio of olaparib to malonic acid is 1: 1; the eutectic X-raypowder diffraction pattern has characteristic peaks when the 2theta value is at the positions of 9.8 + / -0.2 degrees, 12.4 + / -0.2 degrees, 12.6 + / -0.2 degrees, 13.4 + / -0.2 degrees, 16.2 + / -0.2 degrees, 17.5 + / -0.2 degrees, 18.7 + / -0.2 degrees and 21.0 + / -0.2 degrees. The eutectic preparation method is simple in process, easy to control the crystallization process, good in reproducibility and suitable for industrial production. Compared with olaparib free alkali, the eutectic crystal has higher apparent solubility, and is beneficial to improving the oral absorption efficiency of olaparib.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a co-crystal of olaparib and malonic acid and a preparation method thereof. Background technique [0002] Pharmaceutical active ingredients usually exist in crystalline forms, such as polymorphs, hydrates, solvates, salts, and co-crystals. For the same pharmaceutical active ingredient, different crystalline forms have different physical and chemical properties. Therefore, obtaining a suitable crystalline form of a drug is of great importance in the pharmaceutical industry. The drug exists in the form of co-crystal, which can improve the stability, solubility and processability of the active ingredient of the drug, which has significant advantages. Therefore, pharmaceutical co-crystals are an effective means to improve the physicochemical properties of pharmaceutical active ingredients. [0003] The chemical name of Olaparib is 1-(cyclopropylformyl)-4-[5-[(3,4-dihyd...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D237/32A61K31/502A61P35/00C07C55/08C07C51/43
CPCA61P35/00C07B2200/13C07C51/43C07C55/08C07D237/32
Inventor 戴霞林吕文婷陈嘉媚
Owner TIANJIN UNIVERSITY OF TECHNOLOGY
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