贴剂的体外释放与渗透实验方法学及体内外相关性研究进展

The research progress of patch on in vitro release test, in vitro experimental methodology and in vivo-in vitro

贴剂系指原料药物与适宜的材料制成的供贴敷在皮肤上的,可产生全身性或局部作用的一种薄片状柔性制剂。体外释放实验(in vitro release test, IVRT)和体外渗透实验(in vitro permeation test, IVPT)是进行贴剂的处方工艺优化、质量控制和安全有效性评价等临床前药学研究的重要内容。采用的实验设备和方法不同,所得实验样品和数据相互之间有差异,实验数据的准确度与精确度也不一样,因此IVRT&IVPT实验设备的选择和实验方法的建立是贴剂体外实验中一个值得重点关注的问题。本文根据国内外相关研究文献和法规指南,总结了贴剂的研究现状,简要介绍了各国药典对于IVRT的要求,综述了各个方法的差异;对于尚未有相关规范规定实验方法的IVPT,详细介绍了常见的实验设备类型和实验条件,并总结了不同设备的适用性和主要实验条件(温度、搅拌速度,接受液组成,选用的皮肤等)对实验结果的影响,介绍了体内外相关性的研究进展,同时对评判实验数据的有效性进行了探讨,期望为贴剂的体外实验方法学的开发和研究提供有益的借鉴。

Patch refers to a thin sheet flexible preparation made of raw drug and suitable material for sticking on the skin, which can produce systemic or local effects. In vitro release test(IVRT) and in vitro permeation test(IVPT) are important contents of preclinical pharmaceutical research for formulation process optimization, quality control and safety and effectiveness evaluation of patch. The experimental equipment and methods used are different, the obtained experimental samples and data are different from each other, and the accuracy and precision of the experimental data are also different. Therefore, the selection of experimental equipment and the establishment of experimental methods in the in vitro experiment of IVRT & IVPT is a problem worthy of attention. In this paper, the research status of patch was summarized, the requirements of pharmacopoeia of different countries for IVRT experiments were briefly introduced, and the differences of different methods were reviewed. For IVPT experiments that have not yet been prescribed by relevant standards, the common types of experimental equipment and experimental conditions were introduced in detail, the applicability of different equipment and the influence of main experimental conditions(temperature, stirring speed, composition of acceptor solution, selected skin, etc.) on the experimental results were summarized, and the research progress of in vivo and in vitro correlation was introduced. At the same time, the validity of the experimental data was discussed, hoping to provide a useful reference for the development and research of the in vitro experimental methodology of the patch.