Unbound MEDLINE

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.

Abstract

OBJECTIVE
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.
METHOD
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.
RESULTS
A linear increase in solubility of silymarin with respect to the weight fraction of the carrier has been observed.
RESULTS
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).
CONCLUSION
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.

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  • Publisher Full Text

    • Authors

    Hussein A, El-Menshawe S, Afouna M

    Institution

    Department of Pharmaceutics, Minia University, Minia, Egypt.

    Source

    Die Pharmazie 67:3 2012 Mar pg 209-14

    MeSH

    Animals
    Area Under Curve
    Biological Availability
    Calorimetry, Differential Scanning
    Capsules
    Chemistry, Pharmaceutical
    Drug Carriers
    Excipients
    Gelatin
    Half-Life
    Hydrogen-Ion Concentration
    Male
    Polyethylene Glycols
    Protective Agents
    Rabbits
    Silymarin
    Solubility
    Temperature

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22530301