In-vitro diffusion studies to develop and evaluate various semi-solid vaginal bases to optimize miconazloe nitrate release with reduced level of drug

Due to insufficient moisture in the vaginal cavity, the diffusion and dissolution of drug at the site strongly influence the clinical efficacy of the product. This study was undertaken to develop and evaluate various semi-solid dosage forms of Miconazole Nitrate to optimize the release of this hydrophobic drug at the vaginal site.;Formulations containing 2% of Miconazole Nitrate were developed using HPMC gel, nonionic and cationic emulsion based vehicles. Penetration enhancers including propylene glycol, dimethylsxlfoxide and diethyleneglycolmonoethylether at various levels were studied. Diffusion studies were carried out with Franz Diffusion Cells. Using a commercial product as a control, all samples were screened on an equal sample weight basis for the drug release through the cellulose membrane. The formulation with best release was modified to have 1% drug, and this along with the commercial product containing 2% drug were evaluated for 12 hours using human cadaver skin for comparison purposes.;The general order of drug release from three different vehicles was observed to be Cationic emulsion > HPMC > Nonionic system. Among all samples with 2% drug, the cationic emulsion with 5% DMSO gave the maximum release, where the sample exhibited 9% drug release compared to only 3.5% from the control after 2 hours. This formulation was modified to contain (1%) drug, and studied for 12 hours in human cadaver skin against commercial product with 2% drug. Here, the drug release was observed to be 47.3% from the sample and only 10.2% from the control. This represents almost 5 folds increase in the drug release compared to control. These data were used to calculate physical parameters that influence drug diffusion. The values for the steady state flux and diffusion coefficient were the highest from the optimum formulation, and were the lowest for lag time and partition coefficient.;The cationic cream matching the physiological pH with 1% drug gave significantly higher release compared to the commercial product containing 2% drug. This suggests that using an appropriate formulation design, it is possible to enhance the drug release for an optimum clinical efficacy even with the reduced level of drug.