Phytosome Containing Silymarin for Oral Administration: Formulation and Physical Evaluation

Abstract

Silymarin is a unique flavonoid complex isolated from milk thistle (Silybum marianum). It has been widely used as a hepatoprotective agent. Orally administered silymarin can be absorbed rapidly but only 20-50% of silymarin will be absorbed through gastrointestinal tract, resulting in low bioavailability. Those limitations are due to its low solubility, either in water and oil, and its low intestinal permeability. This study was aimed to develop silymarin-containing phytosome in order to improve the bioavailability of silymarin with sufficient safety and stability. This system consisted of silymarin-phospholipid complex prepared by solvent evaporation method, which was incorporated to form phytosome vesicles using thin layer method with various concentrations and molar ratios of silymarin and phospholipid. The vesicle size of phytosome was reduced with sonication. The results demonstrated that formula with 2% silymarin-phospholipid complex and molar ratio of silymarin to phospholipid of 1:5 showed the best phytosomal characteristics, with mean vesicle diameter of 133.534 ± 8.76 nm, polidispersity index of 0.339 ± 0.078, entrapment efficiency of 97.169 ± 2.412 %, and loading capacity of 12.18 ± 0.30 %. The preparation remained stable after freeze-thaw stability test. Analysis of Infrared spectroscopy and Differential Scanning Calorimetry confirmed the presence of physical and chemical interactions between silymarin and phospholipid within complex formation. Well formed and discrete vesicles were revealed by Transmission Electron Microscopy analysis, drug content measurement, and freeze-thaw stability test.