目的 从处方、生产工艺及质量控制提出对热熔挤出(HME)法固体分散体质量评价的考虑,为药物开发提供借鉴。方法 汇总近年来已上市固体分散体制剂,论述关键辅料的种类和作用。介绍HME的处方及生产工艺,提出固体分散体质量控制的基本考虑。结果 HME固体分散体处方中常用辅料种类包括载体基质、增塑剂、表面活性剂及助流剂,已上市制剂所用载体基质主要包括共聚维酮(PVP/VA)、醋酸羟丙甲纤维素琥珀酸酯(HPMCAS)和羟丙基甲基纤维素(HPMC)。HME温度及螺杆捏合是影响固体分散体质量的关键工艺参数。质量控制应关注无定型以及溶出度。结论 重视长期及加速放置条件下固体分散体质量的变化,特别是无定型和溶出度。
Abstract
OBJECTIVE To put forward considerations for the quality evaluation of solid dispersions prepared by hot melt extrusion (HME) from the perspectives of formulation, production process and quality control, and provide reference for pharmaceutical development. METHODS The solid dispersion preparations which have been marketed in recent years were summarized, and the types and functions of key excipients were discussed. The formulation and production process of HME were introduce, and the basic considerations for the quality control of solid dispersions were put forward. RESULTS The types of excipients commonly used in the formulation of HME solid dispersions included carrier matrixes, plasticizers, surfactants, and glidants. The carrier matrixes used in marketed formulations mainly include PVP/VA, HPMCAS, and HPMC. Hot melt extrusion temperature and screw kneading are the key process parameters that affect the quality of solid dispersions. Quality control should focus on amorphous and dissolution. CONCLUSION It is important to pay attention to the change of quality of solid dispersions under long-term and accelerated storage conditions, especially for amorphous and dissolution.
关键词
固体分散体 /
热熔挤出法 /
无定型 /
溶出度 /
质量评价
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Key words
solid dispersion /
HME /
amorphous /
dissolution /
quality evaluation
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中图分类号：
R917
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