Pharmaceutical composition containing sitagliptin or its pharmaceutically acceptable salt and its preparation method and use

Abstract

The invention relates to a pharmaceutical composition, comprising sitagliptin, its pharmaceutically acceptable salt and / or the hydrate of the salt, and anhydrous calcium hydrogen phosphate. The pharmaceutical composition is further used for the preparation of solid preparations, especially tablets by direct compression. By selecting the pharmaceutical composition of the present invention, especially selecting specific anhydrous calcium hydrogen phosphate as a raw material, it is possible to significantly improve the composition of sitagliptin, its pharmaceutically acceptable salt and / or the hydrate of the salt as the active ingredient. The quality control method of the pharmaceutical composition can even significantly improve the generation of related impurities in the pharmaceutical composition, so as to improve the stability of the pharmaceutical composition and related dosage forms.

Description

technical field [0001] The present invention relates to the technical field of pharmaceutical preparations, in particular to a pharmaceutical composition containing sitagliptin or a pharmaceutically acceptable salt thereof, a preparation method and application thereof. Background technique [0002] Sitagliptin (Sitagliptin, CAS No.486460-32-6), chemical name: 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl) Butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine, its structural formula is as follows: [0003] [0004] Sitagliptin Phosphate Tablets is the first DPP-IV inhibitor approved for marketing in the United States for type 2 diabetes. It was originally developed and marketed by Merck. By strengthening the incretin axis, the drug can improve the decreased insulin secretion in the pathogenesis of type 2 diabetes; by reducing the level of glucagon, it can inhibit the excessive production of hepatic glucose, providing a new way for the treatment of t...

AI Technical Summary

Problems solved by technology

The direct compression method is regarded as a relatively fast method, which directly compresses powdery substances (a mixture of drugs and excipients) without changing the physical and chemical properties of the drug. The process is simple and the cost is low. Poor performance, easy to cause stratification between components, making it difficult to apply direct compression method

[0006] Chinese patent application CN106176653A discloses a sitagliptin phosphate pharmaceutical composition and a preparation method thereof, wherein sitagliptin is mixed with a specific auxiliary material in a certain proportion, and the diluent accounts for 50-60% by weight of the entire tablet weight, The specific gravity ratio of microcrystalline cellulose and calcium hydrogen phosphate is 1-1.5, disintegrant 2%, lubricant 4%, tablet granules have defects such as poor fluidity and stickiness caused by the physical and chemical properties of sitagliptin phosphate , the tablet prescription can only be applied to the wet granulation process. Compared with direct compression, the process is complicated, and the moisture in the tablet may affect the stability of the drug. At the same time, adding too much magnesium stearate may affect the dissolution, hardness, etc. of the tablet. influential

However, the process of this embodiment has poor operability, and the tablet weight difference obtained by the experiment is large, and the one-sided glossiness is poor.

Images