脂质体释放度检查方法的标准化研究

发布时间：2019-04-11 11:20

【摘要】：近年来由于脂质体制剂等新剂型的不断研发上市,该类制剂特殊的工艺、构造和性质使其与传统制剂的质控方法有所不同。由于目前无论在脂质体药物的研究、开发方面还是上市药物的质控标准中,释放度测定方法各异、缺乏方法间验证、规范性较差,甚至有的品种的标准未设置释放度测定方法,因此亟需建立并优化该类制剂的质量控制标准,尤其是释放度检查项目,以确保其安全、有效、质量可控。本文首先选择大量专家学者研究的透析法进行研究,通过探究透析法测定的仪器装置,改善检测方法中影响检测结果的不可控因素,使测定装置标准化;同时通过对性质各异的模型药物盐酸多柔比星、硫酸长春新碱、紫杉醇的研究,考察透析法测定脂质体制剂释放度的适用范围和影响透析法释放度测定结果的关键因素,提炼释放度透析测定法建立和验证的基本原则,规范方法建立、验证和使用的基本要求。本文设计和改进了透析膜装置,使其在稳定性、重现性、操作可行性、规范性等方面达到了预期效果,目前在进一步的深入优化中。使用自行设计的透析膜装置考察了透析法测定3种脂质体药物的相关影响因素,获取了验证数据。在此基础上建立了盐酸多柔比星脂质体注射液的释放度透析检测方法,同时总结了透析法的适用性及可行性,为其他脂质体制剂及更多微粒给药系统制剂释放度检测方法的建立提供了基础研究及参考。
[Abstract]:In recent years, due to the continuous research and development of new formulations such as liposomes, the special technology, structure and properties of these preparations make them different from the traditional methods of quality control. At present, both in the research and development of liposomes and in the quality control standards of listed drugs, there are different methods for the determination of release degree, lack of inter-method verification, poor standardization, and even the standard of some varieties does not set up a method for the determination of release degree. Therefore, it is urgent to establish and optimize the quality control standard of this kind of preparation, especially the release inspection item, so as to ensure its safety, effectiveness and quality control. In this paper, we first choose a large number of experts and scholars to study the dialysis method. By exploring the instrument and equipment of the dialysis method, we can improve the uncontrollable factors in the testing method and standardize the measuring device. At the same time, through the study of doxorubicin hydrochloride, vincristine sulfate and paclitaxel, which have different properties, the scope of application of dialysis to determine the release of liposomes and the key factors affecting the results of dialysis were investigated. Basic principles for the establishment and validation of dialysis determination of refining release, and basic requirements for the establishment, verification and use of standardized methods. In this paper, the dialysis membrane device has been designed and improved to achieve the expected effect in the aspects of stability, reproducibility, operation feasibility, standardization and so on. At present, it is in the process of further in-depth optimization. The factors related to the determination of three kinds of liposomes by dialysis were investigated by a self-designed dialysis membrane device, and the verification data were obtained. On this basis, a dialysis method for the determination of the release of doxorubicin hydrochloride liposome injection was established, and the applicability and feasibility of the dialysis method were summarized. It provides a basic research and reference for the determination of the release degree of other liposomes and more microparticle delivery system.
【学位授予单位】：中国食品药品检定研究院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R927

【参考文献】