Biopharmaceutical characterization of topical liposome formulations bearing 5-fluorouracil

Abstract

Liposome dispersions and liposome gel formulations for topical administration were evaluated as modified release delivery systems for 5-fluorouracil. Drug substance has been entrapped in the internal aqueous compartment of liposomes during the preparation. The concentration of 5-fluorouracil in the hydration medium was varied and the effect on the liposome characteristics was considered. Liposome gel formulations were prepared by incorporation of liophylized liposomes into a structured vehicle of chitosan. The decrease of the amount of aqueous phase bearing total drug quantity (drug/aqueous phase ratio from 1:100, 1:60, 1:40) led to an increase of the percentage of liposome-entrapped drug, and decreased percentage of drug release, while particle size analysis showed no changes in vesicle size. Liposome gel formulations showed initially a higher drug release rate in comparision with liposome dispersions, which could be related to the release of “free” 5-fluorouracil, leaked from liposomes due to the process of liophylization. This was followed by slower release (after 1.5 hour) as a result of the influence of the viscosity of the gel matrix.