Topiroxostat tablet and preparation method thereof

Abstract

The invention relates to a topiroxostat tablet. The topiroxostat tablet is prepared by the following steps: grinding effective components and a carrier material through a ball mill to prepare a topiroxostat pharmaceutical composition, carrying out wet granulation, and carrying out tabletting. An effective component in the tablet is topiroxostat, and the tablet comprises the following materials inpercentages by weight: 30% of topiroxostat, 40-68.5% of a carrier material, 2-4% of an adhesive, 2-20% of a disintegrating agent and 0.5-4% of a lubricating agent, wherein the carrier material is composed of a filler and a pH regulator. According to the topiroxostat tablet and the preparation method thereof, tartaric acid or citric acid with proper dosage is added as a pH regulator, and ball milling is carried out at specific grinding time, so that the prepared topiroxostat tablet is high in dissolution rate and high in bioavailability, topiroxostat is limited to be in a crystal form I ratherthan a mixed crystal form, and the stability of the raw materials is ensured.

Description

Technical field [0001] The present invention belongs to the field of pharmaceutical preparations, and specific relates to a cheap tablet and a preparation method thereof. Background technique [0002] Toris, alias: Topiit, Topiroxostat, FYX-051, Chemical Name: 5- (2-cyano-4-pyridyl) -3- (4-pyridyl) -1, 2, 4- Triazole, CAS: 577778-58-6, molecular formula: C13H8N6, its chemical structural formula is as follows: [0003] [0004] Topiroxostat is a new type, highly selective, reversible xanthine oxidase inhibitor. There is inhibitory effect on the xanthine oxidase and the xanthine dehydrogenase, and the uric acid is strong. The drug is not metabolized by kidney, and patients with chronic kidney disease are higher. He was developed by Japan Fuji Yakuhin and the Japan Sanwa Kagaku KenkyuSho. Suitable for gout and high diaper disease. [0005] At present, the clinical main use of allopurinol treatment, while the pest alcohol is a purine analog, which is inevitable to cause influence ...

AI Technical Summary

Problems solved by technology

When the maximum oral dose is 80mg, about 30% of the original drug is excreted through urine or feces, and the bioavailability is poor, which affects the curative effect

[0007] Therefore, how to solve the problem that the dissolution rate of the insoluble drug topicastat is low and affects the bioavailability is a technical problem that those skilled in the art need to solve urgently when developing topicastat preparations

[0008] During the development of existing topinastat preparations, it is mainly divided into the following two categories: ① one is liquid preparations, such as microemulsion technology, cyclodextrin inclusion technology, liposome technology, etc., and this type of technology improves to a certain extent Improve the dissolution rate of poorly soluble drugs, but there are disadvantages of poor stability after long-term storage, for example, after long-term storage, the emulsion will break to a certain extent

②The other type is solid preparations, such as micronization technology, nanocrystal technology, solid dispersion technology, etc. The idea of ​​this type of technology is to increase the dissolution rate by reducing the particle size of the drug, and there is a disadvantage of poor stability caused by the recrystallization of small drug molecules place

The disadvantage of this patent is: due to the specific solubility of topicastat, the injection of this patent has the hidden danger of low dissolution at the release end point and absolute bioavailability

The disadvantages of this patent are: 1. the acid-base regulator used is strongly alkaline or weakly alkaline, and topinastat itself is relatively difficult to dissolve in an alkaline environment, which affects the absorption of drugs and is not conducive to the improvement of bioavailability ② It can be seen from Table 1 of the patent specification that the optimization of the patent’s selection of specific solubilizers, acid-base regulators and other prescription components is aimed at solving the stability problem of the preparation, and it is impossible to improve the bioavailability Known from this patent

The disadvantages of this patent are: ① The prescription optimization of this patent is to solve the stability problem of the preparation, but it is impossible to know whether topicastat is a single crystal or a mixed crystal from its prescription and process, and from its process steps 2) And 3) the possibility of crystal transformation in medium and high temperature and the addition of absolute ethanol can be inferred, which will affect the stability of raw materials; Whether the utilization can be improved cannot be known from the patent

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