Solid dispersoid of amorphous-form Simeprevir or Simeprevir salt acceptable to pharmacy and pharmaceutical auxiliary materials and preparation method of solid dispersoid

Abstract

The invention discloses solid dispersoid of amorphous-form Simeprevir or Simeprevir salt acceptable to pharmacy and pharmaceutical auxiliary materials and a preparation method of the solid dispersoid. The solid dispersoid comprises the Simeprevir or Simeprevir salt acceptable to pharmacy and the pharmaceutical auxiliary materials, wherein the weight ratio of the Simeprevir or Simeprevir salt acceptable to pharmacy to the pharmaceutical auxiliary materials is 1: (0.1-100). The Simeprevir or Simeprevir salt acceptable to pharmacy is in the amorphous form. After a background peak of the pharmaceutical auxiliary materials is deducted from an X-ray powder diffraction spectrum of the solid dispersoid, no characteristic peak of crystals of the Simeprevir or Simeprevir salt is generated. The solid dispersoid of the amorphous-form Simeprevir or Simeprevir salt acceptable to pharmacy and the pharmaceutical auxiliary materials is good in stability and dispersibility; the dissolution rate of the Simeprevir or Simeprevir salt is increased; bioavailability of pharmaceutical preparations and pharmaceutical absorption of organisms can be improved more conveniently; and under the accelerated test conditions, good physical stability and chemical stability can be maintained. The preparation method of the amorphous-form solid dispersoid is simple, low in cost, good in reproducibility, easy to implement and suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a solid dispersion of simeprevir or a pharmaceutically acceptable salt thereof and pharmaceutical auxiliary materials and a preparation method thereof. Background technique [0002] Simeprevir (Simeprevir), the English name is (2R, 3aR, 10Z, 11aS, 12aR, 14aR)-N-(cyclopropylsulfonyl)-2-[[2-(4-isopropyl-1, 3-thiazol-2- yl)-7-methoxy-8-methyl-4-quinolinyl]oxy]-5-methyl-4,14-dioxo 2,3,3a,4,5,6,7,8,9,11a,12,13 ,14,14a tetradecahydrocyclopenta[c]cyclopropa[g] [1,6]diazacyclotetradecinen-12a(1H)-carboxamide, the structure is as follows: [0003] [0004] The trade name of Simeprevir is Olysio, which is an NS3 / 4A protease inhibitor developed by Johnson & Johnson. The U.S. Food and Drug Administration approved the drug in November 2013 for the treatment of chronic hepatitis C infection, antiviral treatment regimens and peginterferon and ribavirin genotype 1 infe...

AI Technical Summary

Problems solved by technology

[0005] Chinese patent CN104230918 discloses simeprevir crystal form I, crystal form II, crystal form III, crystal form IV, crystal form V, crystal form VI, mixtures of different crystal forms, and mixtures of crystal forms and amorphous forms, but there is no Completely amorphous form without crystalline form is reported

However, the patent does not indicate the chemical stability of the amorphous form

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