DESIGN AND DEVELOPMENT OF TRIFAROTENE-LOADED TRANSFERSOMAL GEL USING BOX-BEHNKEN DESIGN

Abstract

The present study aimed to develop and optimize a transferosomal formulation using Design of Experiments
(DoE) and evaluate its suitability for incorporation into a topical gel delivery system. A three-factor, three-
level experimental design was employed to investigate the effects of Soya Phosphatidylcholine (Soya PC)
concentration, ethanol volume, and stirring speed on vesicle size and entrapment efficiency. Thirteen
transferosomal formulations were prepared and evaluated. The entrapment efficiency ranged from 68.2% to
86.8%, while vesicle size varied between 133.4 and 190.5 nm. Formulation F8 was identified as the
optimized formulation, exhibiting an entrapment efficiency of 86.8% and vesicle size of 180.2 nm, which
closely matched the predicted values obtained from the optimization model.
The optimized transferosomes were incorporated into gel formulations and evaluated for viscosity, pH, drug
content, extrudability, and spreadability. Among the developed gels, formulation FG2 exhibited desirable
physicochemical characteristics with a pH of 6.78, viscosity of 9450 cP, drug content of 95.80%, and
satisfactory spreadability and extrudability. In vitro drug release studies demonstrated sustained drug release
over 8 hours, with FG2 showing 91.80% cumulative drug release. Release kinetic analysis revealed that the
formulation followed first-order kinetics (R² = 0.9947) with diffusion-controlled drug release behavior.
Stability studies conducted under refrigerated and room temperature conditions for three weeks indicated no
significant changes in physical appearance or drug content. The findings suggest that the optimized
transferosomal gel is a promising topical drug delivery system capable of enhancing drug entrapment,
providing controlled release, and maintaining stability during storage.