In-vitro release and antifungal activity of ketoconazole from different dermatological vehicles with reduced level of drug

To optimize the clinical efficacy of ketoconazole from dermatological product, this research has been carried out by evaluating drug release/permeation profile from various dermatological vehicles with reduced amount of drug. The optimized formulation was compared against Commercial cream (2%).;Formulations containing 1% w/w drug were developed using 2% HPMC gel, cationic emulsion and non-ionic emulsion as the vehicles. Penetration enhancers like: DMSO (Dimethyl sulfoxide), PG (Propylene glycol) and DGME (Diethylene glycol monoethyl ether) were used at various levels (5%, l0% and 15%). Commercial product 2% w/w ketoconazole cream was used as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for 2 and 6 hours.;Among the formulations evaluated, the general rank order of drug release from these samples through the cellulose membrane was observed to be HPMC gel base > cationic emulsion base > non-ionic emulsion base. In addition, the effects of various penetration enhancers showed variable effects. However, the HPMC gel based vehicle showed significant effect in enhancing the drug release in presence of DMSO. The formulation containing 10% DMSO in gel base gave a maximum drug release of 17.11% when compared to commercial cream which gave 4.57%. Again, the formulation containing 10% DMSO in cationic emulsion base showed around 7.69% release in comparison to commercial cream after 2 hours when cellulose membrane was used as a diffusion barrier. Furthermore, these formulations were studied over an extended period of 6 hours. Formulations with 10% DMSO in gel base and 10% DMSO in cationic emulsion base demonstrated 31.91% and 12.76% in comparison to commercial cream which showed 8.46% release of the drug through cellulose membrane. Finally, these formulations were extended to study on human cadaver skin as diffusion barrier. As anticipated the drug release from both the formulations tested were significantly reduced due to resistance created by the skin. After 6 hours, the drug release from HPMC gel base with 10% DMSO was 3.04°A and from commercial cream 0.55% drug was released after 6 hours. Again, this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their anti-fungal activity using Saccharomyces cerevisiae. The results correlated to the in-vitro drug release profile where both HPMC and cationic cream exhibited greater zone of inhibition than compared to commercial product.;The release data from all the samples were used to calculate various physical parameters including diffusion coefficient, permeability coefficient, partition coefficient, steady state flux and lag period. Surprisingly we observed that from the optimum formulation (IA2 10% DMSO in gel base) the values for diffusion coefficient, and steady state flux were found to be highest and the values for lag time and partition coefficient were lowest. This can be support the fact that the drug from this formulation is readily diffusible to the skin at a steady rate after its application at the site.;In-vitro diffusion studies and anti-fungal studies proved useful in screening various dermatological formulations of ketoconazole compared to commercial product of 2% cream. The HPMC gel base (with 10% DMSO) with reduced level of drug represents more than 5-fold increase through human cadaver skin and improved anti-fungal activity in comparison to 2% commercial cream. This supports that by using an appropriate vehicle and proper incorporation of drug we can optimize the drug release from topical formulation for maximum therapeutic activity.