Investigations of polyethylene glycol mediated ternary molecular inclusion complexes of silymarin with beta cyclodextrins.

ABSTRACT

Objective To evaluate the effect of Polyethylene glycol and β-cyclodextrin on the solubility and dissolution of silymarin, a poorly water soluble herbal drug. Methodology Effects of beta cyclodextrins and Polyethylene glycol on solubility of silymarin were evaluated by phase solubility studies both separately as well as in combination. Solid inclusion complexes of silymarin –β-cyclodextrin in 11 molar ratio were prepared with and without polyethylene glycol by kneading method then evaluated for solubility dissolution and physical nature by XRD, FT-IR and NMR spectroscopy studies. Results The aqueous solubility of silymarin was linearly increased as a function of the concentration of β-cyclodextrin alone and in the presence of polyethylene glycol. Beta cyclodextrin formed molecular inclusion complexes with silymarin in11 molar ratio as revealed by phase solubility diagram. The ternary complexes of silymarin, β-cyclodextrin and polyethylene glycol demonstrated better dissolution than those of silymarin and its binary complexes with β-cyclodextrin alone. Silymarin - β-cyclodextrin complex caused 1.3 fold increase in the dissolution rate of silymarin, which was further increased up to 1.7 fold in presence of small amount of polyethylene glycol. Conclusion The presence of polyethylene glycol markedly enhances the molecular complexation and solubilizing efficiencies of β-cyclodextrin on silymarin.