Quality by Design-based Optimization of Formulation and Process Variables for Controlling Particle Size and Zeta Potential of Spray Dried Incinerated Copper Nanosuspension

Background: In the present study copper nanosuspension was prepared from Incinerated Copper Powder (ICP) by top down media milling. Glycyrrhiza glabra (GG) and Gum Acacia (GA) were used as stabilizers in the formulation. Methods: Box Behnken Design was used to investigate the effect of formulation and process variables on particle size and zeta potential and optimize their ratio to get target product profile. The ratio of GA and GG to ICP was varied along with milling time and its speed. Further the prepared nanosuspensions were solidified using spray drying. Results: The particle size was found to be decreased with the increase in GG to ICP ratio, milling time and milling speed, whereas, reverse effect on particle size was observed with an increase in GA to ICP ratio. The zeta potential was found to be increased with the increase in GG to CB ratio and milling speed and it decreased with the increase in GA to ICP ratio and milling time. The obtained value for particle size was 117.9 nm and zeta potential were -9.46 mV which was in close agreement with the predicted values by the design which was, 121.86 nm for particle size and -8.07 mV for zeta potential respectively. This indicated the reliability of optimization procedure. The percentage drug loading of copper in the nanosuspension was 88.26%. The micromeritic evaluation of obtained spray dried nanoparticles revealed that the particles were having good flow and compactibility. Conclusion: It can be concluded that application of media milling, design of experiment and spray drying have offered very good copper nanosuspension that has the potential to be scaled up on industrial scale.