Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II.

Objective: To prepare and optimize the topical elastic liposome (EL)-loaded carbopol-980 gel of 5-Fluorouracil (5-FU) containing permeation enhancers (azone, propylene glycol (PG) and lauryl alcohol (LA)) and further evaluation for permeation flux of 5-FU, the activation energy and irritation in the rat skin.

Methods: EL formulations were prepared using phosphatidylcholine and varied surfactants (Span 60, Span 80 and Tween-80) by rotator evaporation method and optimized by experimental design. In vitro characterizations dictated the EL containing Span 80 (lipid:surfactant = 7:3) (EL3-S80) for further optimization of gel. Different gel formulations (5% w/w) with varying concentration (1-3%) of permeation enhancers were prepared and evaluated for viscosity, spreadability, the 5-FU permeation and deposition. The activation energy using the Franz diffusion cell and the plausible irritation using the Draize test were assessed on the albino rat and rabbit, respectively.

Results And Discussion: EL3-S80 was selected as an optimized EL owing to maximum desirability (0.99) and enhanced 5-FU flux (187.86 ± 14.1 μg/cm(2)/h). EL3-S80 suspension loaded gels (0.5%) revealed reduced viscosity leading to higher spreadability than blank gel. EL containing 3% azone in gel, EL containing 3% LA in gel and EL containing 3% PG in gel portrayed 187.86 ± 14.1, 117.7 ± 13.4 and 106.7 ± 7.3 μg/cm(2)/h as enhanced 5-FU flux values, respectively as compared to drug solution (8.8 ± 0.76 μg/cm(2)/h). Furthermore, reduced value of activation energy (2.63-folds) and the non-irritancy of gel could be effective and safe.

Conclusion: ELA-3 gel formulation could be used as an effective and economic gel in cutaneous cancer and skin-related keratoses.