Preparation and Characterization of Silymarin Synchronized and Sustained Release Dropping Pill.

PURPOSE: This study aimed to develop a synchronized and sustained-release silymarin dropping pill, and to evaluate its pharmacokinetic characteristics. METHOD: Polyoxyethylene stearate, glyceryl monostearate, and stearic acid were used to prepare the dropping pills. X-ray powder diffraction, differential scanning calorimetry, and release were used to evaluate its physicochemical properties. The plasma concentration of silybin in beagle dogs after oral administration of silymarin dropping pills and silymarin capsule was determined by RP-HPLC. RESULTS: Synchronized release was achieved with high similarity factor f2 values between every set of two of the five components. Mean plasma concentration-time curves of silymarin after oral administration of dropping pills in beagle dogs were in accordance with first-order absorption and open twocompartment model. The Tmax, Cmax, and AUC0-∞ of dropping pills in beagle dogs were 0.8750±0.13 h, 0.8183±0.07 µg·ml-1, and 2.274±0.90 µg·h·ml-1, respectively. Silymarin dropping pills prolonged in vivo exposure and reduced maximum in vivo concentration, achieving a stable level in the serum. CONCLUSION: The combination of solid dispersion technique and dropping pill formulation allowed synchronized release of multiple components in herbal medicine, and has potential application in the development of sustained release in herbal medicine.

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

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 f 2 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.