Skin delivery of Propylthiouracil from vesicular systems

Abstract

Vesicular systems are known to improve skin delivery of many drugs with diversity in solubility. The mechanism of skin delivery of these systems is inconclusive and likely to depend on the drug delivered. The aim of this present study was to investigate the skin delivery of a model lyophobic drug from vesicular systems. The study focused on skin delivery mechanism and the factors affecting skin permeation from vesicular systems. In this study, propylthiouracil (PTU) was used as a model lyophobic drug. Three vesicular systems containing PTU, i.e. liposomes, niosomes, and ethosomes, were prepared and characterized with regard to size and size distribution, drug entrapment efficiency, phase transition temperature, and drug release. The skin delivery of PTU from vesicular systems was studied using modified Franz diffusion cells. The newborn pig skin was used as a membrane. The results demonstrated that the vesicle size and the drug entrapment efficiency of PTU vesicular systems depended on the composition of the system. All PTU vesicular systems were in liquid crystalline-state at the temperature used in the study. Drug release studies revealed that all vesicular systems could sustain the release of PTU and the release was consistent with the first order kinetics. The 24-hour cumulative percent release of PTU up to 90% was achieved. In skin permeation study under the non-occlusive condition, the liposomal systems did not enhance PTU permeation through the skin, while the niosomal system and the ethosomal systems were likely to improve PTU skin delivery. The application condition had a considerable impact on skin permeation of PTU from the ethosomal systems. The ethosomal systems were thus selected for further investigation under the occlusive condition. The effect of existence of vesicular structure on PTU permeation from ethosomes was less remarkable than the synergistic enhancing effect of the ethosomal components and the solvent used in the study. Analysis of the data from characterization and skin permeation studies under the occlusive condition indicated that the diffusion of free drug, the mixing of the vesicles with the skin lipids, and the penetration enhancement were all possible to occur in skin permeation of PTU from the ethosomal systems. Therefore, skin delivery of PTU from the ethosomal systems appeared to involved several mechanisms that operated simultaneously.