Tanshinol sustained-release pellets with absorption enhancer: optimization, characterization, pharmacokinetics and pharmacodynamics.

The objective of this study was to develop tanshinol sustained-release pellets (TS-SRPs) for the treatment of angina. Considering the poor intestinal absorption of TS, sodium caprate (SC) was used as an absorption enhancer for bioavailability improvement. Single-pass intestinal perfusion in rats demonstrated that the permeability of TS was remarkably enhanced, when the weight ratio of TS to SC was 1:3. Then, the cores were prepared with TS, SC and MCC at a weight ratio of 1:3:16 via extrusion-spheronization, followed by coating with Eudragit(®) RS30D/RL30D dispersion (9:1, w/w). In vitro release studies revealed that release methods and rotation rates had no significant effects on the drug release of optimized TS-SC-SRPs except for the dissolution media. The release behavior was characterized as non-Fick diffusion mechanism. The pellets possessed a dispersion-layered spherical structure and were stable during three months of storage at 40 °C/75% RH. Compared with TS immediate-release pellets, the AUC0-24 in healthy rabbits was increased by 1.97-fold with prolonged MRT (p < .05). Pharmacodynamic studies in rabbits with angina showed that the optimized TS-SC-SRPs had a steady and improved efficacy with synchronous drug concentration-efficacy. Consequently, preparation of sustained-release pellets with absorption enhancer provides a potential strategy to prolong the release and enhance the efficacy for hydrophilic drugs with poor intestinal absorption.