DESIGN, OPTIMIZATION, AND EVALUATION OF A LORNOXICAM-LOADED TRANSETHOSOMAL GEL FOR ENHANCED TRANSDERMAL DELIVERY

Objective: Lornoxicam is an effective oxicam-class non-steroidal anti-inflammatory agent administered in the managing acute & chronic inflammatory conditions. However, its oral administration is inadequate by deprived aqueous solubility, extensive first-pass metabolism, & gastrointestinal adverse effects. Transdermal drug delivery offers a promising alternative by bypassing hepatic metabolism and enabling sustained drug release, although the stratum corneum restricts effective drug permeation. Transethosomes, ultradeformable vesicular carriers, have shown considerable potential in enhancing transdermal drug transport. Methods: Lornoxicam-loaded transethosomes were obtained by the cold method & optimized by3-factor, 3-level Box–Behnken design. Phospholipid (soya lecithin), surfactant (Tween 80), & ethanol concentrations selected as independent attributes, vesicle size and entrapment efficiency (EE) evaluated as critical responses. Optimized composition fused intoCarbopol-934 gel base & characterized for physicochemical properties, vesicle morphology, zeta potential, in vitro drug release, in vitro permeation, & short-term stability. Results: Optimization studies demonstrated that phospholipid and surfactant concentrations majorly impacted vesicle size &%EE, whereas ethanol played huge role in enhancing membrane fluidity and permeation. The optimized formulation (LRNX-12) exhibited nanosized vesicles (179 nm), improved (81.8%), & a favorable negative zeta potential (−34.6 mV), indicating good stability. Transmission Electron Microscopy analysis confirmed spherical vesicles with smooth morphology consistent with entrapment. The release data were fitted to zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. The highest correlation coefficient was obtained for the Higuchi model (R² = 0.97), indicating diffusion-controlled release. In vitro permeation studies showed significantly higher drug permeation from the transethosomal gel (93% at 24 h) compared with the conventional plain gel (45%). The gel showed acceptable pH, viscosity, spreadability, and good stability. Conclusion: The lornoxicam-loaded transethosomal gel demonstrated enhanced transdermal delivery with sustained release and superior permeation, offering a promising alternative to oral therapy for inflammatory conditions.