Sofosbuvir pharmaceutical composition as well as preparation method and application thereof

Abstract

The invention relates to a sofosbuvir pharmaceutical composition as well as a preparation method and application thereof. One purpose of the invention is to provide a preparation method of a pharmaceutical composition of sofosbuvir or a derivative thereof, which comprises the following steps: (1) mixing sofosbuvir or a derivative thereof with a pharmaceutically acceptable carrier to prepare a premix, and then carrying out secondary dry granulation on the premix to prepare an inner particle part, the pharmaceutically acceptable carrier is selected from any one or a combination of a diluent, a disintegrating agent, a flow aid and a lubricant; and (2) mixing the intra-particle part prepared in the step (1) with an extra-particle pharmaceutically acceptable carrier to prepare a total mixture, tabletting and coating to obtain the tablet, and the pharmaceutically acceptable carrier is selected from any one or a combination of a diluent, a disintegrating agent, a flow aid and a lubricant. The preparation method of the pharmaceutical composition of sofosbuvir or the derivative of sofosbuvir improves bulk density and fluidity of granules, and the quality of the obtained product is controllable.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a sofosbuvir pharmaceutical composition and a preparation method and application thereof. Background technique [0002] The global prevalence of HCV infection is high and there is a lack of effective treatments. The "standard regimen" of hepatitis C treatment is peginterferon combined with ribavirin, but this regimen will cause many adverse reactions and be ineffective for some patients. Sofosbuvir (see formula I for structure) is a hepatitis C treatment drug with significant clinical efficacy. [0003] [0004] The particle size and bulk density of the sofosbuvir API are small and prone to electrostatic agglomeration, which affects its dispersibility, and is quite different from the particle size and bulk density of the pharmaceutically acceptable carrier, which leads to uneven mixing and affects the quality of the preparation. uniformity, which in turn affects the effic...

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Problems solved by technology

[0004] The particle size and bulk density of the sofosbuvir raw material drug are small and prone to electrostatic agglomeration, which affects its dispersibility, and the particle size and bulk density of the pharmaceutically acceptable carrier are quite different, resulting in uneven mixing and affecting the quality of the preparation Uniformity, which in turn affects the effectiveness and safety of clinical treatment

[0005] CN104039319A adopts dry granulation method to prepare Sofosbuvir tablet, this method comprises steps such as premixing, dry granulation, total mixing, tabletting, coating and packing, and adopts the dry granulation machine with separator, by The separator section separates the granules into three categories (coarse, acceptable and fine) where the coarse granules are treated with "Comil" and the acceptable granules go to the blending step; while the fine granules are re-granulated through the roller compactor , and then granulated, repeating the process until a minimum amount (for example, less than 20%) of fine particles remains, and it is necessary to separate the fine powder for many times and repeat the granulation; there are agglomerates in the pre-mixture, which affects the raw material drug and pharmaceutical The homogeneous mixing of acceptable carriers affects the uniformity of the formulation, the process is cumbersome and unstable, and is not suitable for industrial production

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