Objective: Solubility is a key parameter as it is one of the main causes for poor bioavailability. The objective was to improve the solubility and dissolution profile of poorly-soluble silymarin with a water-soluble carrier fulvic acid. Materials and methods: Phase solubility studies were carried out for the determination of stoichiometric ratio between silymarin and fulvic acid by Higuchi and Connors method. The binary systems made by physical mixing and kneading methods were characterized by drug content, solubility studies, solid-state characterization by DSC, FT-IR, dissolution studies and ex vivo permeation studies. Results and discussion: The phase-solubility studies between silymarin and fulvic acid revealed AL type of curve, indicating linear increase in drug solubility with increase in carrier concentration and from these apparent stability constant and Gibbs free energy transfer values were calculated. It was found that the reaction conditions became more favorable as the concentration of fulvic acid increased from 0.2% to 2% w/v, indicating the spontaneity of solubilization process at higher carrier concentrations. Physical mixture and kneading showed increased solubility and dissolution rates compared with pure drug. In DSC, no melting peak of silymarin was seen, indicating that it was in amorphous form inside the carrier and FT-IR studies demonstrated interactions between drug and carrier. Conclusion: Improvement in solubility, dissolution profiles and permeation was observed in physical mixture and kneading as compared to pure drug establishing the role of fulvic acid as a promising carrier which can be used to formulate silymarin with better in vitro and in vivo performances.
Shamama Javed, Kanchan Kohli and Waquar Ahsan