维生素K_(1)混合胶束包封率测定方法的适用性研究

Applicability Study of Determination Methods for Encapsulation Efficiency of Vitamin K_(1)-loaded Mixed Micelles

维生素K_(1)(VK_(1))混合胶束(VK_(1)-MM)注射液中游离的VK_(1)会导致安全性风险,包封率可评价混合胶束中游离VK_(1)的量以及胶束的载药性能。该研究比较了萃取法、离心法和过滤法用于测量VK_(1)-MM包封率的适用性,并讨论了不同方法中影响包封率测定准确性的主要因素。结果表明,萃取法中使用的萃取剂会影响VK_(1)-MM的结构;游离VK_(1)与水的密度差异较小,导致离心法不能彻底分离游离VK_(1)和VK_(1)-MM;过滤法选用合适的滤膜孔径及材质时,可有效分离游离VK_(1)和VK_(1)-MM,且方法回收率为100.40%(RSD0.80%,n=3),适用于测定VK_(1)-MM的包封率。该研究对不同包封率测定方法的原理及待测样品特性的适用性分析结果为其他胶束制剂建立科学、合理、适用的包封率评价方法提供了参考。

Free vitamin K_(1)(VK_(1))in VK_(1)-loaded mixed micelles(VK_(1)-MM)injection leads to security risks.The encapsulation efficiency is one of the indexes to evaluate the content of free VK_(1)in mixed micelles and their drug-loading performance,while the applicability of various determination methods is different.This study compared the applicability of extraction,centrifugation,and filtration methods in evaluating the encapsulation efficiency of VK_(1)-MM.The study of the main factor affecting the accuracy of each method showed that the extractant altered the structure of VK_(1)-MM during extraction.In addition,the free VK_(1)and VK_(1)-MM could not be completely separated by centrifugation,which was related to the tiny density difference between free VK_(1)and water.However,filtration could effectively separate free VK_(1)and VK_(1)-MM with the appropriate pore size and material of the filter membrane.The recovery of filtration was 100.40%(with RSD of 0.80%,n=3),which showed filtration was suitable for determining the encapsulation efficiency of VK_(1)-MM.Simultaneously,the applicability of different encapsulation efficiency determination methods and the characteristics of formulations were analyzed,which provided a reference for establishing a suitable encapsulation efficiency determination method for other micellar preparations.