Design and Hepatoprotective Evaluation of Biphenyl Dimethyl Dicarboxylate (DDB) and Silymarin Solid Dispersion and Self-Micro Emulsifying Drug Delivery Systems

Biphenyl Dimethyl Dicarboxylate (DDB) and Silymarin are widely used drugs for the treatment of hepatitis C virus, have poor bioavailability due to their low aqueous solubility that limits their dissolution rates. To overcome these limitations solid dispersions (SDs) and self-microemulsifing drug delivery systems (SMEDDS) were prepared in an attempt to improve their release profile. SDs were prepared using co-precipitation and melting methods at various drug-polymer ratios. Polyethylene glycol (PEG 6000), polyvinylpyrrolidone (PVP K30 and PVP K17) or sodium desoxycholate were used to prepare SDs by co-precipitation method. PEG 4000, PEG 6000 or poloxamers (F68 and F127) were used to prepare SDs by melting method. On the other hand, Ternary phase diagram was constructed using Miglyol 812 (oil), Tween 80 (surfactant), Transcutol HP (co-surfactant) and water to identify the efficient self-microemulsification region. In-vitro release studies were studied for the prepared SDs and SMEDDS. DDB release from all prepared SDs did not show any significant improvement when compared to their corresponding commercial product except for the melts prepared by poloxamer F68 used in 1:5 drug to carrier weight ratio. Silymarin release from all SDs was significantly improved when compared to their corresponding physical mixture, Silymarin powder or its commercial product. Silymarin:Sodium desoxycholate with 1:3 weight ratio, gave the highest drug dissolution behaviour. On the other hand, it was found that the optimal formulation with the best Self-microemulsifying and dissolution behaviour for DDB or Silymarin consisted of 10% Miglyol 812, 40% Tween 80, and 50% Transcutol HP. This formulation showed higher extends of DBB or Silymarin release compared to their powder or commercial products. The optimized formulations of DDB or Silymarin SDs and SMEDDS were evaluated regarding their hepatoprotective activity against carbon tetrachloride-induced oxidative stress in Albino rats when challenged with commercial products DBB pillules and Mariagon capsules. These develobed formulations might be useful in the prevention of used successfully hepatic fibrosis. [Hanan. M. Ellaithy, Yassin. E. Hamza and Soha. M. Kandil. Design and Hepatoprotective Evaluation of Biphenyl Dimethyl Dicarboxylate (DDB) and Silymarin Solid Dispersion and Self-Micro Emulsifying Drug Delivery Systems. Life Science Journal. 2011;8(1):298-310] (ISSN:1097–8135). http://www.lifesciencesite.com.