Synchronized and controlled release of multiple components in silymarin achieved by the osmotic release strategy.

The pharmacological activity of herbal medicines is determined by the active components ratio that defines the medicine. Significant alteration of the components ratio will lead to major changes in the pharmacological activities. In designing sustained or controlled release delivery systems of herbal medicines, we developed the concept of synchronized release which was characterized by keeping active components' initial ratio throughout the whole release process. In this study, this concept was extended by developing a novel synchronized release system based on osmotic release strategy, which was designed as a monolithic osmotic tablet consisting of a tablet core and semi-permeable coating of cellulose acetate with mechanically perforated release orifices. The rationale of synchronized release lies in simultaneous release of silymarin multiple components in a solubilized state through the release orifices. To ensure quick solubilization of multiple components, silymarin was first formulated as fast-release solid dispersion before formulating into the osmotic tablet. The concept of synchronized release was well proved by the results of high similarity of the release profiles of the five active components in silymarin (taxifolin, silychristin, silydianin, silybin and isosilybin). Zero-order release profiles can be maintained up to approximately 20 h. High synchronicity and controlled release can be achieved by adjusting the formulation variables. It is indicated that the osmotic release strategy has great potential to achieve synchronized and controlled release of multiple components in herbal medicines.