Perspective Impact of Gelling Agents on the Mechanistic Behavior for the Topical Delivery of Flufenamic Acid Nano-Ethosomal Dispersion

Abstract

Objective: This work involves the preparation and in vitro characterization of a topical gel formulation that is capable of deep skin permeation, providing the anti-inflammatory effect for the optimum nano ethosomal dispersion formula. Methods: The optimum ethosomal dispersion was prepared (in our laboratory) by utilizing 3% flufenamic acid (FA), 30% ethanol, 1% phosphatidylcholine (PC), 10% propylene glycol, and 1% cholesterol by cold method and 20 minutes’ ultra-sonication. Four ethosomal gel formulas (G1-G4) were prepared by using carbopol 934 and carbopol 940 at 1% and 1.5% concentration at a 1:1 ratio as a gelling agent. These formulas were further subjected to in vitro characterization to assess their physical appearance, consistency, viscosity, spreadability, in vitro drug release, and ex-vivo skin permeation and deposition. Results: The results revealed that the formula (G1) demonstrated the best homogeneity, consistency, and spreadability as well as an initial release of 68.53% after 10 hours, that continued up to 89.36% after 24 hours, and a significantly higher drug release percentage at pH 7.4 than pH 5.5 with substantially higher ex vivo abdominal rat skin permeation (60.74%) and deposition percentages (36.87%%) in comparison to flufenamic acid plain gel prepared conventionally which demonstrated 23.73% and 14.96% skin permeation and deposition percentages after 24 hours. Conclusion: This work was successful in preparing a novel topical gel using ethosomal nanocarriers, promoting efficient topical skin delivery of the anti-inflammatory FA with a once-daily application, which improved patient compliance.