Optimizing the Formula of Polymeric-Based Aripiprazole Nanosuspension Using Response Surface Methodology for Intranasal Drug Delivery

This study aimed to optimize the formula of aripiprazole nanosuspension for intranasal drug delivery. Response Surface Methodology (RSM) was employed to determine the influence of independent variables, including drug concentration, polymer concentration, and the ratio of polymer combination, on the nanosuspension characteristics. The parameters under investigation were particle size (d mean), polydispersity index, and drug content. Fifteen formulas were prepared using the high-shear homogenization–ultrasonication method, and the Design Expert software was applied for optimum formula determination. The result showed significant effects of the independent variables on the nanosuspension characteristics, with particle sizes ranging from 143.6 – 334.6 nm, PDI values of 0.302 – 0.649, and drug content was 98.7 – 102.1 %. The predicted optimum formula had a drug concentration of 28 mg/mL in the organic solvent, polymer concentration of 1.5% (w/v), and HPMC to PVP ratio of 1.4 with desirability of 0.94. Additionally, it exhibited desirable characteristics, such as a particle size of 171.2  11.4 nm, a PDI value of 0.317  0.02, and a high drug content of 100.04  0.65%. In conclusion, the presented methodology appeared to be perfect for the optimization of the aripiprazole nanosuspension formula to ensure suitability for nose-to-brain drug delivery.