他扎罗汀凝胶处方及微观结构特性评价的比较研究

Comparative study on the ingredients and microstructure arrangement of tazarotene gel

目的为他扎罗汀凝胶一致性评价处方工艺设计及关键质量属性评价提供指导。方法逆向解析原研产品ZORAC^(■)和国产仿制药产品乐为^(■)处方,比较处方(Q_(1))和关键辅料的处方用量(Q_(2))差异;并采用光学显微镜和流变仪考察粒度、流变特性等微观结构特性(Q3)差异。结果国产仿制药产品乐为^(■)与原研产品ZORAC^(■)均为“非牛顿流体”,均属于弱性凝胶,但在稳定剂种类及用量、活性成分晶体形态、流变特性、pH值等5个关键质量属性方面差异显著,说明两者产品Q_(1)、Q_(2)及Q3均不一致,推测Q_(1)、Q_(2)和工艺设计不同引起Q3差异。结论本研究可用于指导国内生产企业优化处方工艺设计,为皮肤外用半固体制剂一致性评价提供研究思路。

Objective To provide guidance for the formulation process design and the evaluation of critical quality attributes of tazarotene gel consistency.Methods The ingredients of the original product ZORAC^(■)and domestic generic drug乐为^(■)were analysized by reverse engineering,and the differences between qualitative(Q_(1))and quantitative(Q_(2))compositions of inactive ingredients were compared.The differences in microstructure arrangement(Q3)were investigated by an optical microscope and rheometer,such as particle size and rheological properties.Results Both ZORAC^(■)and乐为^(■)were“non-Newtonian fluids”and belong to weak gels.However,there were significant differences in five critical quality attributes,such as the type and amount of stabilizer,crystal morphology of the active ingredient,rheological properties,and pH value,which indicated that the Q_(1),Q_(2),and Q3 of the two products were inconsistent.It was suggested that the wide variations in Q3 were caused by the differences in Q_(1),Q_(2),and process design.Conclusion It was significant for this study to optimize formulation development,and provide research ideas for consistency evaluation of semisolid preparations for topical skin use.