Preparation and characterization of silymarin synchronized-release microporous osmotic pump tablets

Abstract

The pharmacological activity of herbal medicine is an overall action of each component in accordance with their original proportion. An efficient, sustained, and controlled-release drug delivery system of herbal medicine should ensure the synchronized drug release of each active component during the entire release procedure. In this study, silymarin (SM), a poorly soluble herbal medicine, was selected as a model drug to develop a synchronized-release drug delivery system: an SM microporous osmotic pump (MPOP) tablet. The SM was conjugated with phospholipid (SM phytosome complex, SM-PC) to improve the solubility, and the difference in the apparent octanol–water partition coefficient between the two components was significantly reduced. The dissolution rate of SM-PC was significantly higher than SM active pharmaceutical ingredients and was the same as that of the commercial SM capsule. The SM-PC was used to generate the MPOP tablet. SM was mixed with poly(ethylene) oxide and sodium chloride (an osmotic agent) to form the MPOP core, followed by coating with cellulose acetate and poly(ethylene) oxide to generate the SM MPOP. The results demonstrated that SM MPOP could synchronically and sustainably release the five active components within 12 hours (the similar coefficient f₂ between two components was >65), and the average cumulative release rate was 85%. Fitting of the drug-release curve showed a zero-order release profile for SM MPOP. Our study showed that the phytosome complex technique combined with the MPOP system will achieve synchronized release of the various active components of herbal medicine and have potential applications in developing sustained release preparations in herbal medicine.

Keywords:

• silymarin
• synchronized release
• sustained release
• phytosome complex
• microporous osmotic pump tablets
• dissolution test

Supplementary material

Table S1 Statistical analyses of the release profile among three drugs

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No 81073064) and Natural Science Foundation of Fujian Province of China (No 2015J01491).

Authors contributions

All authors made substantial contributions to conception and design, Dr Qi-ping Zeng and Zhi-hong Liu performed research and acquired data. Dr Ai-wen Huang and Dr Jing Zhang undertook analysis and interpretation of data. All authors took part in either drafting the article or revising it critically for important intellectual content. All authors gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.