口服固体药物制剂体外溶出度的高时间分辨在线过程分析

Rapid and accurate on-line analysis of oral solid dosage form dissolution in vitro, which assesses the dissolution speed and degree of the active pharmaceutical ingredients from drugs, is of vital importance in various aspects including drug research and development, controlling and evaluating drug quality, assessing quality and efficacy consistency of generic drugs, etc., and is also a challenging research topic. In this proposal, we will perform high temporal resolution on-line analysis of dissolution processes of different oral drugs based on high-speed capillary electrophoresis (HSCE). The research of the proposal will focus on establishing a novel on-line analysis method which combines the flow-through cell technique for dynamic simulation of body fluid, the automatic sequential sample injection technique, and the HSCE technique for separation and detection. Using this method, we are going to achieve sensitive on-line measurements on the dissolution processes of various kinds of oral drugs, with temporal resolution of tens of seconds to even seconds, to obtain the relation between the dissolution experiments in vitro and the bioavailability in vivo, and finally to explore the quality difference and efficacy consistency of generic and original drugs. The purpose of the proposal is to develop a new on-line analysis method to monitor the real process of drug dissolution, and to further expand the application of the CE technique in various fields of pharmaceutical research, drug regulation and clinical analysis.

快速准确地对口服固体药物制剂的体外溶出过程进行在线分析，评价活性药物成分的溶出速度和程度，对药物研发、药物质量控制与评价、仿制药质量和疗效一致性评价等方面具有重要意义，同时也是一项极具挑战性的研究课题。本项目拟基于高速毛细管电泳技术，针对不同剂型的口服固体药物制剂，开展高时间分辨的体外溶出过程在线分析。重点将建立集动态模拟体液循环的流通池技术、自动序列进样技术、以及高速毛细管电泳分离检测技术为一体的新型药物溶出过程在线分析方法，并利用该分析方法对不同类型药物的溶出过程实现数十秒乃至数秒量级时间分辨的准实时监测和高灵敏分析，获取体外溶出度试验与体内生物利用度的相关性，进而探索仿制药与原研药质量差异以及药效一致性。项目旨在建立有效的研究药物体外溶出过程的在线分析方法，监控药物释放的真实过程，进一步拓展毛细管电泳技术在药学研究、药物监管和以及临床分析中的应用。

快速准确地对口服固体药物制剂的体外溶出过程进行在线分析，评价活性药物成分的溶出速度和程度，对药物研发、药物质量控制与评价、仿制药质量和疗效一致性评价等方面具有重要意义，同时也是一项极具挑战性的研究课题。在项目执行期间，我们结合动态模拟体液循环的流通池、自动序列进样、以及HSCE分离检测技术，建立了高时间分辨在线分析技术方法，用于口服固体药物体外溶出过程检测，实现对固体口服药物的溶出分析及药效评价，同时针对集成化、微型化和自动化的在线溶出分析开展研究，研发了便携的药物溶出分析仪，可实现药物中不同有效成分溶出过程的在线分析，不仅具有高时间分辨、高效分离和自动化分析，同时高度集成，使用方便且造价低，有望在药物研发中发挥重要作用。同时，围绕项目相关方向我们亦开展了创新研究，在新型微反应器、生物传感器、分离分析技术对生物和药物物质的高灵敏检测等方面，取得了一些有价值的创新成果，为进一步的研究夯实了基础，提供了新的研究思路。