Preparation and Evaluation of pH‐Dependent Gradient‐Release Pellets for TCM

Abstract

This paper is designed to investigate a novel sustained release system for Traditional Chinese Medicinal Compound Recipe (TCMCR) by incorporating three kinds of pH‐dependent gradient‐release coated pellets into capsules. In our study, dosage reform was conducted on the TCMCR model drug–Guanxin Suhe Wan (GSW), which is in the traditional form of honey bolus, comprising Styrax, Borneolumsyntheticum, Olbanum, Radix aristolochiae and Lignum santali albi. In this study, the β‐CD inclusion complexes were prepared separately for Styrax, Borneolumsyntheticum and the volatile oil extracted from the mixture of Olbanum, Radix aristolochiae and Lignum santali albi. Pellets were prepared in a centrifugal granulator using the powder layering technique and then divided into 3 equal weight portions and coated with HPMC, HPMCP HP‐55 and Eudragit L100/S100 to obtain gradient release in stomach, duodenum and jejunum or ileum respectively. On this basis, a pH‐dependent sustained‐release pellets system, “Guanxin Suhe Sustained‐release Capsules”(GSSC), was prepared by mixing the above three kinds of coated pellets at the weight ratio of 1:1:1. Pharmacokinetic (PK) studies between GSW and GSSC were made on male volunteers and isolated guinea pig hearts by plasma drug concentration method and serum pharmacology method respectively. In plasma drug concentration method, T_max was 0.42 h and 1.08 h for GSW and GSSC respectively, while in the serum pharmacology method, T_max was 0.56 h and 0.52 h respectively. The relative bioavailability of GSSC to GSW was 95.62% and 121.82% separately in the above two methods, indicating a similarity between the two methods in predicting the PK behavior of GSSC.