Evaluation of drug release & anti-bacterial activity of metronidazole from dermatological bases using reduced level of the drug.

摘要

To optimize the clinical efficacy of metronidazole 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 gel and Cream.;Formulations containing 0.4% w/w drug were developed using 2 % 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 0.75% w/w metronidazole cream and gel respectively were included as a controls 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. 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 the presence of Urea. The formulation containing 0.4 % w/w metronidazole and 5% w/w Urea gave a maximum drug release of 37.9 % when compared to 21.2% from the commercial gel. And Anionic emulsion base with PG 10 % gave a release about 14% when compared to 7 % commercial cream. These represents a twofold increase in the release of metronidazole from the formulations. Furthermore, these formulations were studies over an extended period of 12 hours , it gave 63 % drug release from HPMC gel base compared to over 32 % from commercial gel and 23.2 % from anionic cream base against 14 % 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 HPMC gel base is 1.13% & commercial gel is 0.57 % and Anionic emulsion base is 2.55 % & commercial cream is 0.79 % . Once again this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their antibacterial effects using Periodontal bacteria. The results correlated to the in-vitro drug release profile, where both HPMC & Anionic cream exhibited greater zone of inhibition than compared to commercial products.;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 antibacterial studies proved useful in screening various dermatological formulations of Metronidazole compared to commercial products containing 0.75 % gel and cream . The HPMC & Anionic based formulation with reduced level of drug represents more than two fold increase through human cadaver skin and augmented antibacterial 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.