Optimizing Nimesulide Loaded Cubosomal Gel for Enhanced Efficacy: A Systematic Engineering Approach with Factorial Design for Topical Applications

The primary aim of this study is to develop a cubosome nanoformulation for the optimized delivery of nimesulide, with a focus on improving its efficacy and reducing adverse effects. The ultimate goal is to advance the pharmaceutical application of nimesulide by achieving sustained release kinetics.

A systematic approach was employed to develop nine cubosomal formulations using a top-down strategy with the primary focus on optimizing the lipid (glyceryl monooleate - GMO: X₁) and surfactant (Pluronic F-127 - PF-127: X₂) concentrations. The selection of these variables was based on a 3²-factorial design. The impact of varying concentrations of GMO and PF-127 on critical parameters such as particle size distribution and entrapment efficiency were thoroughly investigated.

The optimized formulation demonstrated favorable characteristics, including a particle size ranging from 153.5 ± 4.99 to 199.6 ± 10.23 nm, and EE between 70.5 ± 1.85 to 88 ± 2.17%. Zeta potential values ranged from − 35.6 to -40.5 mV, while PDI values fell within the range of 0.32 to 0.51. In vitro investigations revealed a meticulously sustained drug release profile with regulated kinetics observed over a 24 h period. Rheological studies provided insights into the viscoelastic behaviour and structural integrity of the cubosomal gel formulation. Ex vivo absorption studies conducted on goat skin demonstrated superior drug absorption and sustained release patterns compared to a commercially available gel.

The study concludes that the application of nimesulide-loaded cubosomal gel has the potential to enhance drug absorption and facilitate sustained release. This nanoformulation presents a promising strategy for improving the topical delivery of nimesulide while minimizing adverse effects.