New crystal form of topirastat and preparation method thereof

Abstract

The invention belongs to the field of chemical pharmaceutical technologies, and particularly relates to a novel topiroxostat crystal form. 2-theta characteristic peaks in X-ray powder diffraction patterns of the novel topiroxostat crystal form are positioned at 5.38+ / -0.2, 8.29+ / -0.2, 10.78+ / -0.2, 15.46+ / -0.2, 21.59+ / -0.2 and 26.88+ / -0.2 degrees. The invention further provides a method for preparing the novel topiroxostat crystal form. The method includes adding topiroxostat into organic solvents; adding alkali into the organic solvents; stirring the topiroxostat and the alkali in the organic solvents until that solid clearly dissolves; adding activated carbon for color removal; filtering the organic solvents to obtain filter liquid; dripping acid in the filter liquid to adjust pH (potential of hydrogen) of the filter liquid until the pH of the filter liquid reaches 6-7; dissolving solid out of the filter liquid; performing extraction filtration on the filter liquid to obtain filter cakes; leaching the filter cakes; drying the filter cakes to obtain the novel topiroxostat crystal form. The novel topiroxostat crystal form and the method have the advantages that the novel topiroxostat crystal form is good in thermal stability and high in wet stability and solubility; products are high in purity, are quite suitable for long-term storage and are suitable for preparing solid preparations with good dissolution and / or stability; the products prepared by the aid of the method have the single and stable crystal form and are quite suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of chemical industry and pharmacy, and in particular relates to a new crystal form of topirastat and a preparation method thereof. Background technique [0002] 4-[5-(Pyridin-4-yl)-1H-[1,2,4]triazol-3-yl]pyridine-2-carbonitrile, Chinese name: Topirostat, English name: Topiroxostat, commodity Name: TOPILORIC, is a non-purine xanthine oxidoreductase selective inhibitor for the treatment of gout, hyperuricemia. It was jointly developed by Japan Fuji Pharmaceutical Co., Ltd. and Sanwa Chemical Research Institute. In June 2012, it submitted a marketing application to the Ministry of Health, Labor and Welfare of Japan. On June 28, 2013, Topirastat tablets were approved. [0003] The chemical structure of 4-[5-(pyridin-4-yl)-1H-[1,2,4]triazol-3-yl]pyridine-2-carbonitrile (Topiroxostat) is as follows: [0004] [0005] Japan Fuji Pharmaceutical Co., Ltd. first disclosed this compound and its synthesis route in ...

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Problems solved by technology

[0005] Japan Fuji Pharmaceutical Co., Ltd. first disclosed this compound and its synthesis route in patent CN1561340, and disclosed two crystal forms of topirastat and a hydrate in patent WO2014014515. The patent introduces that crystal form I is in The solubility in water is 6.2 μg / ml, the solubility of crystal form II is 4.2 μg / ml, and the solubility of hydrate is 1.9 μg / ml. It can be seen that topirastat is a drug that is difficult to dissolve in water. Compared with crystal form II and hydrate, crystal form I of sestat has a higher solubility and is the preferred crystal form in preparations. However, it is reported in the patent CN104042577 that in the process of tablet compression, there is mutual interaction between form I and form II. The phenomenon of crystal transformation, the transformation of crystal form has a potential impact on the dissolution rate and stability of pharmaceutical preparations, the above-mentioned properties of topirastat make it have a huge potential in the preparation of solid preparations with good dissolution and / or stability challenge

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