艾曲波帕片的制备和溶出度评价

Preparation and Dissolution Behavior of Eltrombopag Tablets

以艾曲波帕(1)自制片和参比制剂Promacta在含0.2%Tween-80的pH 6.8磷酸盐缓冲液(PBS)中溶出曲线的相似因子(f2)为主要考察指标,采用单因素试验筛选了自制片处方;用正交设计优化了制粒工艺。采用优化后的处方工艺制备3批小试1片,分别比较了其与参比制剂在pH 1.0盐酸、pH 4.5乙酸盐缓冲液、pH 6.8磷酸盐缓冲液和水4种介质中的溶出行为相似性,用相似因子法进行评价。结果表明,4种介质中的f_2值均大于56,说明自制片与参比制剂体外溶出行为相似;且各批次间差异较小,说明处方工艺稳定,可进行进一步的放大研究。

The dissolution profiles of self-made eltrombopag （1） tablets and the reference preparation, Promacta, in pH 6.8 phosphate buffer containing 0.2 % Tween-80 were investigated, and their similarity factor （f2） values were calculate to optimize the formulation of the self-made tablets. The formulation of self-made 1 tablets was optimized by a single factor test, while the preparation of wet granulation was optimized by an orthogonal design test. The results showed that the optimal formulation was as follows： the ratio of mannitol to microcrystalline cellulose （MCC） was 1 ： 2.25, and amounts of polyvinylpyrrolidone （PVP） K30 and sodium carboxy methyl starch （CMS-Na） were 1% and 10%. During the preparation of wet granules, the granulation time, stirring speed and chopping speed were 200 s, 300 r/min and 1 000 r/rain, respectively. Three batches of the self-made 1 tablets were prepared according to the above findings. Then, the dissolution behaviors of the self-made 1 tablets and Promacta in four media including hydrochloric acid solution （pH 1.0）, acetate buffer solution （pH 4.5） and phosphate buffer solution （pH 6.8） and water were determined. And the calculated f2 values between two preparations in four media were all above 56. It revealed that the dissolution behavior of the self-made product was similar to that of Promacta. In addition, the batch-to-batch difference was small. The results showed that the formulation and preparation of the self-made 1 tablets were both stable and practical.