Clinical Pharmacokinetic Profiles of Hanmi SMEDDS Silymarin Soft Capsule Preparation

Silibinin(silybin) is the active component of silymarin from Silybum marianum and has hepatoprotective effect. It is water-insoluble and has low bioavailability. To improve its bioavailability, self-microemulsifying drug delivery system (SMEDDS) has been developed by Hanmi Pharmaceutical Company (Silyman^R 140 soft capsule). In this study, the pharmacokinetic profiles of Silyman^R were examined and compared it with a reference preparation, L Caps 140 of B Pharmaceutical Company. This study was approved by Yonsei University Severance Hospital IRB(approval No. CR0004) and followed the bioequivalence test guideline of Korean FDA. Eighteen healthy adult volunteers were allocated based on 2 x 2 Latin square cross-over design. They were given 2 capsules (each contains silymarin 140 mg (60 mg as silibinin)) of either drug at each period and crossed over after a week of drug-free washout period. Blood concentration of silibinin was measured by HPLC. The C_(maX) and AUC of the Silyman^R were 1542.0±402.7 ng/ml and 3323.3 e±824.7 ng·h/ml, respectively, and were significantly higher than those of reference preparation. The T_(max) was 0.8±0.3 h and significantly shorter than reference preparation. The K_e and T_½ of both drugs were comparable. Percent differences in means against reference preparation were +88.3% for AUC, +222.6% for C_(max), and -61.1 % for T_(max).ope