Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X1, Span 40; X2, and sonication time; X3) on the responses (particle size, Y1, and entrapment efficiency, Y2). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (p p p p max and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.
