BOX–BEHNKEN DESIGN APPROACH FOR OPTIMIZATION OF ACECLOFENC LOADED TRANSFEROSOMAL GEL FOR ENHANCED TRANSDERMAL DELIVERY

Objective: The current study aimed to develop and optimize an aceclofenac (ACF)-loaded transferosomal gel for transdermal drug delivery using a Box–Behnken design (BBD), thereby enhancing bioavailability and reducing systemic side effects. Methods: Using different ratios of Span 80 and phosphatidylcholine (PDC), transferosomes were developed using the rotary thin-film hydration method and optimized with BBD. The independent variables in transferosome preparation were the amount of Span 80 and PDC. The dependent variables were entrapment efficiency (EE), drug release (DR), and drug content (DC). Drug and excipient compatibility were determined using differential scanning calorimetry and Fourier transform infrared spectroscopy. The prepared transferosomes were characterized for DC, particle size distribution, EE, zeta potential, polydispersity index (PDI), in vitro DR and morphology by scanning electron microscopy (SEM). The optimized ACF transferosomal formulation was incorporated into a gel and evaluated for pH, spreadability, viscosity, ex vivo skin permeation, and stability. Results: The optimized formulation had a spherical shape, a vesicular size of 157±27.16 nm, a PDI of 0.26±0.058, and an EE of 89.69±4.2%. The optimized transferosomal gel showed an ex vivo permeation of 3900±57.21 μg/cm2 over 24 h through the skin of albino Wistar rats. SEM demonstrated the smooth surface. The DR kinetics adhered to a zero-order model, showing a sustained release pattern and confirming improved transdermal penetration of ACF through transferosome technology. Conclusion: Transferosomes are effective nanoscale carriers for ACF, significantly enhancing the transdermal penetration of ACF through transferosome technology as confirmed by ex vivo skin permeation studies.