Development, Optimization, and Evaluation of a Salicylic Acid-Loaded Transferosomal Gel for Enhanced Topical Management of Acne Vulgaris

Background: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit, and salicylic acid is one of the most widely used topical keratolytic agents for its management. However, conventional topical formulations of salicylic acid show limited penetration across the stratum corneum, restricted follicular residence time, and require frequent application. Objective: The present study aimed to develop, optimize and evaluate a salicylic acid-loaded transferosomal gel as an ultra-deformable vesicular carrier for improved skin penetration and sustained topical delivery of the drug. Methods: Preformulation studies (organoleptic evaluation, solubility, melting point, UV calibration and FTIR) were performed on salicylic acid. Transferosomal vesicles were prepared by the ethanol injection method using soya lecithin, cholesterol and Tween 80, and eight batches (F1–F8) were evaluated for appearance, pH, vesicle size, polydispersity index (PDI), entrapment efficiency, deformability index and drug content. The optimized suspension was incorporated into Carbopol 934 gel bases (G1–G5) and evaluated for appearance, homogeneity, pH, viscosity, spreadability, gel consistency, drug content, in vitro drug release, FTIR drug–excipient compatibility, zeta potential and SEM morphology. Release data were fitted to zero-order, first-order, Higuchi and Korsmeyer–Peppas kinetic models. Results: Formulation F6 emerged as the optimized transferosomal suspension, with a mean vesicle size of 158 nm, PDI of 0.108, entrapment efficiency of 93.00 ± 0.72%, deformability index of 92.41 ± 0.86%, and drug content of 96.8%. Among the gel batches, G5 (1.5% w/w Carbopol 934) was optimized, showing a smooth, homogeneous, translucent appearance, pH of 5.66, spreadability of 133.93 g·cm/s, homogeneity index of 99.89%, and drug content of 97.5%. FTIR spectra confirmed retention of all characteristic salicylic acid peaks in the optimized gel with only minor shifts (≤ 7 cm⁻¹), indicating drug–excipient compatibility. In vitro release from G5 was sustained, reaching 97.34% at 12 h, and best fitted the Korsmeyer–Peppas model (R² = 0.9945), indicating a diffusion-controlled, non-Fickian release mechanism. Conclusion: A salicylic acid-loaded transferosomal gel with desirable physicochemical, rheological and sustained drug-release properties was successfully developed, representing a promising patient-compliant alternative to conventional topical formulations for acne management.