Enhancement of the in-vitro dissolution and in-vivo oral bioavailability of silymarin from liquid-filled hard gelatin capsules of semisolid dispersion using Gelucire 44/14 as a carrier.
The purpose of this study was to improve peroral bioavailability of the very poorly water-soluble hepatoprotectant silymarin through formation of semisolid dispersion (SD) system with Gelucire 44/14.
Binary SD systems were prepared by the solvent-fusion method and confirmed by differential scanning calorimetry (DSC). The solubility and in vitro release at pH values of 1.2 and 7.4 were then determined. The pharmacokinetic parameters and relative bioavailability of orally administrated silymarin pure (SP), silymarin-Gelucire 44/14 SD (GL) capsules were assessed and compared to that of Hepaticum (silybin-cyclodextrin) capsules (CP) as a reference standard (RF) using New Zealand albino rabbits.
A linear increase in solubility of silymarin with respect to the weight fraction of the carrier has been observed.
The solubility of silymarin SD increased - 1.5-to-7-fold (relative to pure silymarin) at 1-to-15% of Gelucire 44/14 which in turn dramatically increased the dissolution rate of silymarin-Gelucire SD (91% within 10 min). The DSC study showed complete disappearance of the silymarin endothermic peak confirming formation of silymarin SD. In the bioavailability study, SD of silymarin with Gelucire 44/14 profoundly increased the AUC(0-12) and C(max) values (-13-fold relative to RS).
The solubility and dissolution pattern of silymarin were found to be carrier ratio dependent. Moreover, the in vitro solubility and dissolution data established very good correlation with the calculated in vivo pharmacokinetic parameters. The ratios between the mean AUC(0-12) for GL capsules and that of CP capsules was significantly higher (156.2%). However, the Tmax values of the three formulations remained eventually unchanged.
Department of Pharmaceutics, Minia University, Minia, Egypt.
SourceDie Pharmazie 67:3 2012 Mar pg 209-14
Area Under Curve
Calorimetry, Differential Scanning
Pub Type(s)Journal Article