Reinvestigating nanoprecipitationvia Box Benhken Design: A systematic approach

Abstract

This work demonstrates Box Benhken design (BBD)’s capability in exploring scientific principles governing a process, different from its use in process optimization. We have investigated nanoprecipitation (NP) of temozolomide with polycaprolactone. Five factors, surfactant, stirring speed (SS), dropping rate (DR), phase volume ratio (PVR) and drug polymer ratio (DPR) were varied over three levels. Corresponding particle size (238.9±42.24 nm), zeta potential (ZP, -5.92±3.15 mV) poly dispersity index (PDI, 0.176±0.06)) and entrapment efficiency (EE, 65.74±9.83%) were put into different polynomial equations. Analysis of variance, lack of fit tests and regression analysis was applied on these equations to determine theone with best fit. This selected equation was subsequently adapted as the model to describe influence of factors on NP. 3D response surface plots corresponding to models and diagnostic plots relatable to normality of residuals were also constructed. In conclusion, application of BBD efficiently strategized experimental foray conducted to elucidate nanoprecipitation.