SYSTEMATIC DEVELOPMENT OF BINARY ETHOSOMAL NSAID BASED GEL

The present study describes formulation optimization, ­in-vitro evaluation and ex-vivo assessment of indomethacin loaded binary ethosomal gel using central composite design. Two formulation factors, concentration of lipid and concentration of ethanol were optimized for their effects on vesicle size (Y₁), zeta potential (Y₂), polydispersity index (Y₃), entrapment efficiency (Y₄) and % cumulative drug release (Y₅). The lipid concentration was found to significantly affect particle size, zeta potential and in-vitro drug release and ethanol concentration was found to significantly affect zeta potential while the interaction effects varied with each response. On identification of optimum desirability, an optimized formulation was prepared, characterized and loaded into transdermal gel. The optimized ethosomal formulation showed observed values for Y₁, Y₂, Y₃, Y₄ and Y₅ of 185.5nm, -27mV, 0.237, 87.86% and 45.65% respectively. Ethosomal gels were formulated using carbopol and HPMC and were characterized for pH, spreadability, drug content, viscosity, and % CDR wherein the optimized formulation showed values of 6.85, 31.07 g.cm/sec, 99.87%, 52000cP, and 56.11% respectively. Ex-vivo permeation study for the optimized ethosomal gel was conducted and the drug permeation mechanism was identified. Skin irritation studies performed on Wistar Albino rats showed no erythema or oedema. Stability studies at -20 °C and 2-8 °C showed satisfactory results. Comparison of in-vitro drug release from ethosomal gel and marketed gel depicted that formulated ethosomal gel improved permeation of drugs. Hence, ethosomal formulation could be considered a suitable drug delivery system especially when loaded into transdermal vehicles with a possible reduction in side effects and improvement in drug permeation.