Development and Characterization of Silymarin Phospholipid Complex for Improved Solubility, and Toxicological Evaluation in Experimental Animals

Objectives: The silymarin phytosome (SPY) was developed to improve the solubility and dissolution. The prepared phytosome was evaluated for hemolytic, membrane stabilization activity, and in vivo acute and subchronic toxicity. Materials and Methods: The toxicological evaluation was carried out by assessing its effects on liver, kidney, brain, lungs, heart and spleen in a rat model. In addition to confirmation of formation of phytosome, the physical-chemical characterization was done by FTIR, DSC, PXRD, and 1H NMR. Results: The optimized formulation has higher aqueous solubility of SPY compared to that of pure silymarin. The formulation also exhibited a significantly higher rate and extent of silymarin release in dissolution studies. The percent hemolysis for SPY was significantly less than silymarin. As a result, SPY can be concluded to be non-toxic and biocompatible for in vivo administration. SPY significantly inhibited hypotonic solutioninduced hemolysis in a dose-dependent manner. In acute oral toxicity, no treatment-related death or toxic signs were observed. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination revealed no abnormalities. Conclusion: The study shows that SPY is a promising and viable strategy for improving the delivery of silymarin.