Ketorolac tromethamine is a drug with narrow therapeutic index and short biological half-life. This study was aimed at developing and optimizing proniosomal formulation of ketorolac tromethamine in order to improve its bioavailability. The prepared proniosomal gel formulations were evaluated and the effect of the varying composition of non ionic surfactant and cholesterol in various formulations were studied, such as vesicle shape, zeta potential, entrapment efficiency, and in- vitro drug release study. The presence of cholesterol made the proniosomes more stable with high drug entrapment efficiency and retention properties. The highest entrapment efficiency was observed with sodium cholate 88.17 ± 0.95 as compared to those formulation prepared with span60 and with sodium deoxycholate. Formulation F1 (LCI-I), zeta potential value was observed -20.0 mV, which is a measure of net charge of proniosomes which made them stable, by preventing aggregation. Formulation  F1 which prepared by sodium cholate, showed highest drug release of 94.048 % after 24 hrs as compared to formulation F6 (LDCI-3) and F9 (LSI-3) which were prepared by sodium deoxycholate and sapn60 showed lowest drug release of 76.35% and 69.12%
