The current study deals with the development and optimization of Losartan Potassium (LP) loaded nanoparticles by continuous flow microreactor precipitation methodology for sustained release. Formulation of LP loaded nanoparticles was conducted by using box Behnken (3(3)) experimental design to evaluate the effect of three independent process variables viz., polymer concentration (Ethyl cellulose, Xi), surfactant concentration (Tween 80, X-2) and the inner diameter (1(3) of the microreactor on the preferred responses: encapsulation efficiency (Y-1) and drug release (Y-2) over 12 h. The average particle size and polydispersity index of LP loaded nanoparticles were characterized by particle size analyzer. The interaction between ethyl cellulose and the LP was investigated by FTIR spectroscopy. The surface morphology and physical nature of LP loaded nanoparticle were characterized by FESEM and XRD analysis, respectively. The design formulations showed the encapsulation efficiency within the range of 57.5 to 82.8% with sustained release profile of 77.2 to 100% over 12 h. The actual and predicted values of both the responses were close to each other. It is verified that the Box Behnken factorial design provides a useful platform for the optimization of LP loaded nanoparticle by microreactor precipitation methodology. (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.