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

Abstract

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 AUC_0–24 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.

Keywords:

• Tanshinol
• sodium caprate
• sustained-release pellets
• optimization
• pharmacokinetics
• pharmacodynamics

Acknowledgements

The authors thank ISP, FMC and Evonik corporations for providing the excipients.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Additional information

Funding

This work was financially supported by National Natural Science Foundation of China (No. 81473151) and the Priority Academic Program Development of Jiangsu Higher Education Institutions.