Establishment of Dissolution Test Method for Multi-Components in Traditional Chinese Medicine Preparations Based on In Vitro–In Vivo Correlation

Abstract

In this study, a multi-component integrated dissolution evaluation system of Yuanhu Zhitong tablets (YZTs) was established based on in vitro and in vivo correlation (IVIVC). The dissolution tests of five quality markers (Q-markers), including tetrahydropalmatine, α-allocryptopine, protopine, corydaline, and byakangelicin, in YZTs were conducted under different dissolution conditions, and pharmacokinetic studies were performed in beagle dogs to construct a correlation model using numerical deconvolution. The data of the five ingredients were integrated in vitro and in vivo according to the biopharmaceutical classification system (BCS) to establish an IVIVC integrating multiple Q-markers. The dissolution media with the best correlation of components were obtained and validated. The results showed that all five components were classified as BCS I compounds, and α-allocryptopine, byakangelicin, tetrahydropalmatine, and corydaline showed good correlation in the paddle method, 75 rpm, with dissolution media of artificial gastric fluid, acetate buffer, acetate buffer and 0.1 M HCl, respectively. Protopine showed good correlation in the paddle method, 100 rpm, with dissolution media of 0.1 M HCl. The integrated BCS I Q-markers showed the best correlation in the medium of acetate buffer. The multi-component integrated dissolution evaluation system established in this experiment accurately predicted the pharmacokinetic data of YZTs by verifying the media, which can be used for the quality control of YZTs. The present study provides an effective and promising strategy for the dissolution evaluation for traditional Chinese medicine preparations.

Keywords

• quality control
• dissolution condition
• multi-component integration
• Yuanhu Zhitong tablet
• biopharmaceutic classification system