Abstract

Contagious infections caused by the Herpes simplex virus are globally known to be lifelong, with periodic re-activation. Available medications have limitations in terms of poor oral bioavailability and lower efficacy on topical administration. No preventive or therapeutic vaccine has been developed till date. The aim of the study is to develop and optimize Penciclovir topical formulations with enhanced drug delivery to the site and improved onset of action. Based on Penciclovir-solubility, different oils and surfactants were screened. Concentrations of mineral oil, polysorbate 20 and labrafil M1944 were chosen based on pseudoternary phase diagrams. The optimized Penciclovir-Nano emulsion through I-Optimal design contains Smix and oil in concentrations of 16 %-21 % and 5 %-25 %, respectively. Results obtained for transmittance, droplet size, and zeta potential are 90.2 %-97.5 %, 64-450 nm, and 12-42 mV, respectively. Nano-emulsion gel was prepared using optimized Penciclovir-Nano emulsion and different types and variations in concentration levels of gelling agents. Higher concentrations of gelling agents enhance the rheological properties of Penciclovir- Nano-emulsion gel. The Penciclovir-Nano-emulsion gel formulation (Carpool 940 at 1.8 % w/w) has shown an improved drug release profile in comparison with Penciclovir-cream and free Penciclovir-gel. Ex vivo permeability studies were performed using human Cadaver skin, the enhancement factors of 1.87 and 1.49 were obtained against free Penciclovir-gel and Penciclovir-cream, respectively. In silico drug permeation studies were conducted using a developed human skin model, and the LogP of the optimized formulation was determined, revealing a significant change compared to the cream and free drug formulations.