直接压片法制备琥珀酸索利那新片的混合工艺考察

Blending Process of Solifenacin Succinate Tablets by Direct Compression

采用粉末直接压片法制备小规格的琥珀酸索利那新(1)片。以总混物料含量均匀性为评价指标,采用单因素和正交设计优化原辅料的预处理方法和混合工艺参数。确定原料药粒径是影响混合均匀性的最显著因素,优化的混合工艺为控制原料药d(0.9)不大于120μm,1先与羟丙甲纤维素预混,再加入淀粉乳糖(Star Lae,过60目筛),在混合频率24 Hz下混合3 min,最后加入硬脂酸镁混合3 min。工艺验证时制备了3批1片,每批10 000片,每片含1 5 mg,考察压片过程中的物料分离情况和所得片剂的含量均匀度。结果表明,本工艺能保证物料具有良好的混合均匀性且在压片过程中不会产生分离现象。

The small-dose solifenacin succinate tablets were prepared by direct compression. The pretreatment methods for bulk drug and excipients and blending process parameters were optimized with the content uniformity of the mixed powder as the index by single factor test and orthogonal design. According to the results, particle size of the bulk drug was confirmed as the most significant factor affecting the blending uniformity. The optimal blending process was as follows： the particle size d（0.9） should be controlled to below 120μm; then the bulk drug was pre-blended with hypromellose, followed by adding StarLac passed through a 60 mesh sieve and mixing at blending frequency of 24 Hz for 3 min; finally magnesium stearate was blended with the mixture for 3 min before tabletting. Three batches of solifenacin succinate （5 mg） tablets were prepared in a batch production of 10 000 tablets to investigate the segregation of the blended mixture and the content uniformity of the tablets at the different sampling time points during compression. The results showed that this blending process could ensure the materials with good homogeneity, and there was no observation of segregation in the process of tablet compression.