FORMULATION AND EVALUATION OF ETODOLAC-LOADED ETHOSOMAL GEL FOR DEEPER DERMAL DELIVERY IN THE MANAGEMENT OF CHRONIC INFLAMMATIONQ

Abstract

Etodolac is a non-steroidal anti-inflammatory drug widely used in the treatment of pain and inflammation. Oral administration of Etodolac is often associated with gastrointestinal side effects and first-pass metabolism, while conventional topical formulations may show limited skin penetration.The present study aimed to formulate and evaluate an Etodolac-loaded ethosomal gel for enhanced topical drug delivery and sustained drug release.Etodolac-loaded Ethosomes were prepared by the cold method using ethanol, soya lecithin, propylene glycol, and distilled water. Nine formulations (F1–F9) were developed by varying the concentrations of lecithin and propylene glycol. The prepared ethosomes were evaluated for encapsulation efficiency and in vitro drug release. The optimized formulation was further characterised for particle size, polydispersity index (PDI), and zeta potential, and then incorporated into a Carbopol 940 gel base. The resulting ethosomal gel was evaluated for pH, spreadability, viscosity, drug content, and skin irritation. Drug release kinetics were analysed using zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. Diffusion studies for both the prepared Etodolac ethosomal gel and the marketed Proxym (Etodolac) gelwere compared.  Among all formulations, F9 was found to be the optimized formulation, showing the highest encapsulation efficiency of 95.72 ± 0.28% and maximum cumulative drug release of 96.67% at 12 h. The optimized formulation exhibited a particle size of 328.1 nm, PDI of 0.507, and zeta potential of -40.0 mV, indicating nanosized vesicles with good physical stability. The ethosomal gel showed satisfactory physicochemical properties, with pH 6.0, spreadability 6.65 g·cm/sec, drug content 99.52%, viscosity 48,750 ± 320 cps, and no signs of skin irritation. Release kinetic analysis revealed that the optimized formulation best followed zero-order kinetics.Drug diffusion from prepared Etodolac ethosomal gel found as 96.4%, and that of marketed preparation found as 82.6%. The developed Etodolac-loaded ethosomal gel demonstrated satisfactory formulation characteristics, high drug encapsulation, nanosized vesicle formation, good stability, and sustained drug release. The study suggests that ethosomal gel is a promising topical delivery system for Etodolac, with potential to improve therapeutic efficacy and better release from the marketed preparation.