Abstract:
The aim of this work was to develop a microemulsion based hydrogel (MBH)
formulation for topical d r u g delivery of ketoconazole with an objective to
increase the solubility of Ketoconazole which is an azole antifungal agent. The
study was also undertaken to overcome the drawbacks associated with oral
drug delivery systems such as poor solubility of drugs, drug degradation in
gastric environment, hepatic first pass metabolism and gastrointestinal irritation.
Selection of oil was done on the HLB value and solubility. Capmul MCM EP,
tween 80 and isopropyl alcohol (IPA) were selected as oil, surfactant and cosurfactant
respectively for preparation of microemulsion. Pseudoternary phase
diagrams were constructed at various tween 80 and IPA ratios. The 2:1 ratio
represented greater area of microemulsification. Microemulsions were prepared
by water titaration method. The prepared microemulsion was optimized on the
basis of droplet size, zeta potential and drug release. The optimized
microemulsion was further evaluated for % transmittance, pH, viscosity,
conductivity, drug content and stability study. The HPMC (Hydroxy Propyl Methyl Cellulose) K100M (1.5%w/v) was slowly
mixed with optimized microemulsion under stirring for the preparation of
MBH. The developed MBH contained Ketoconazole (1% w/w), Capmul MCM
EP (6.25%w/w), tween 80 and isopropyl alcohol (40% w/w, 2:1), Water (53.75
%w/w) and HPMC K100M (1.5%w/v). The optimized MBH was evaluated for
viscosity, spreadability, drug content, skin irritancy and skin permeability. The
mechanism of drug release from MBH was observed to follow zero order
kinetics on the basis of R2 value (Regression Coefficient) of various
mathematical kinetics models. The antifungal activity of MBH was compared
with marketed Ketoconazole cream and it was found that the zone of inhibition
for MBH was found to be comparable with marketed cream. Thus, the MBH
was successfully formulated for topical delivery to treat fungal skin infections.
