In this study we aimed to determine the optimum conditions for sonication in the manufacture of nanostructured lipid carriers (NLC). NLC were developed using a mixture of palm stearin and palm olein, water, and tween as surfactants. The optimum conditions of NLC is defined as having a size below 200 nm, a zeta potential of +30 mV, and a polydispersity index below 0.5. We used response surface methodology with a Box- Behnken experimental design to obtain the optimum conditions for the production of NLC. The independent variables used in this study were amplitude (X-1, kHz), pulse on pulse off (X-2, minute), and time of sonication (X-3, minute), each having three levels. The zeta potential (Y-1, mV), polydispersity index (Y-2), and particle size (Y-3, nm) were used as the dependent variables. The dependent variables were determined by dynamic light scattering using a Malvern Zetasizer Nano ZS. The closest to optimum formulation was obtained at a combination of 35 kHz amplitude, pulses on 9 pulses off 3, and 3 min 25 seconds sonication. This regime resulted in the production of NLCs with a particle size 127.9 nm, a polydispersity index of 0.191, and a zeta potential of -27.3 mV.