Evaluation of drug release & anti-fungal activity of econazole nitrate from dermatological bases using reduced level of the drug.

摘要

To optimize the clinical efficacy of Econazole nitrate from dermatological product, this research has undertaken by evaluating drug release/permeation profile from various dermatological vehicles with reduced amount of drug. The optimized formulations are compared against Commercial Cream.;Formulations containing 0.5% w/w drug were developed using HPMC gel, Non ionic emulsion and Anionic emulsion as the vehicles. Penetration enhancers using propylene glycol (PG), dimethylsulfoxide (DMSO) and urea at various levels were evaluated. Commercial products 1% w/w Econazole nitrate cream was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and twelve hour studies.;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 > Nonionic emulsion base > Anionic emulsion base, but due to instability next best formulation was considered "Nonionic emulsion . In addition, the effects of various penetration enhancers showed variable effects. However Non-ionic emulsion with DMSO as penetration enhancer gave the best release . The formulation containing 0.5 % w/w Econazole nitrate and 15% w/w DMSO gave a maximum drug release of 40.33% when compared to 2.99% from the commercial cream. This represents a tenfold increase in the release of Econazole nitrate from the formulations. Furthermore, these formulations were studies over an extended period of 12 hours, it gave 63.60% drug release from Non-ionic cream base compared to over 6.50% from commercial cream . Finally these formulation are extended to study on human cadaver skin as diffusion barrier. As expected the drug release from both the formulations tested were significantly reduced due to resistance posed by skin. After 12 hours the drug release from non-ionic cream base was 9.47% & commercial cream is 3.98 % . Once again this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their antifungal effects using yeast . The results correlated to the in-vitro drug release profile, where Non-ionic cream exhibited greater zone of inhibition than compared to commercial product.;The release data from all the samples were treated to calculate various physical parameters including diffusion coefficient, permeability coefficient, partition coefficient, steady state flux and lag period etc. Interestingly, the values for the steady state flux and diffusion coefficient were found to be highest from the optimum formulation and the values for the lag time and partition coefficient were lowest. This supports the evidence that the drug from this formulation is readily diffusible to the skin at a steady rate after its application at the site.;In-vitro drug diffusion studies and in-vitro antifungal studies proved useful in screening various dermatological formulations of Econazole nitrate compared to commercial products containing 1 % cream. The Non-ionic cream based formulation with reduced level of drug represents more than two fold increase through human cadaver skin and augmented antifungal activity. This supports that by using an appropriate vehicle and proper incorporation of drug, one can optimize the drug release from topical formulation for maximum therapeutic effect.