Phenytoin ( diphenlhydantoin), a hydantoin derivatives that has long been for its use in epilepsy, Clinical data indicate that systemic or topical phentoin enhances the healing of various types of wounds and chronic ulcers. This pushes us to formulate and optimize some topical dermatological formulations containing phentyoin (PHT) or its sodium salt for treatment of certain skin healing. Dermal films, creams and ointment of phenytoin sodium were designed and developed for the first time by in vitro and clinical evaluation. Dermal patches of phenytoin sodium were prepared by solvent evaporation technique using different concentration of Hydroxypropyl, methylcellulose (HPMC) and Hydroxypropyl cellulose (HPC). Characterization of phenytoin creams and ointment were evaluated from the point of view of drug content, viscosity measurements and drug release studies. Moreover all topical formulations under investigation were evaluated for their physicochemical characteristics; the possible drug-polymer interaction by DSC
and IR studies and kinetic release studies. In vivo evaluation was to evaluate and compare dermal phenytoin patch with phenytoin powder and normal saline in healing of chronic skin ulcer in diabetic patients. Assessment of the ulcers was done statistically weekly interval up to 12 weeks. Patients with post deep acne scars were assigned to PHT cream, placebo cream and microdermabrasion alone. Photographs of ulcers and scars were taken at baseline and at the end of treatment.The results show that, the thickness as well as the weight of the patch increased with the increase in polymer concentration and there was no interaction between the polymers and the drug. In vitro release studies shows that, HPMC enhanced the release rate of phenytoin sodium from prepared films and the drug release followed Higuchi
and first order kinetics. The ulcer volume reduction of the phenytoin patch group was greater and statistically significant comparing with phenytoin powder and control groups. Phenytoin patch appears to be the most stable and effective topical formula in the healing of chronic diabetic ulcer.The results of the phenytoin release from ointment bases showed that emulsion based ointment exhibited the higher phenytoin release as well as lower viscosity than other formulations. Therefore it was selected for further evaluation because of its lower viscosity, easy to remove from the skin, creamy in nature and higher release of phenytoin . On the other hand, the release of phenytoin from cold cream bases increase as the borax concentration increased. Kinetic studies revealed that the best fitted model for phenytoin selected formula was Higuchi kinetic model. The clinical investigation revealed a significant difference between phenytoin ointments treated group and other groups and has proven that, phenytoin ointment help in better and faster resolution of the acne lesion as well as in reducing inflammation