The achievement of desirable pharmacokinetic parameters from particulate drug delivery systems are dependent on the physical characteristics of the systems namely, particle dimension, loading of therapeutic agent, encapsulation efficiency, in vitro release kinetics. This study aimed to evaluate the main and interaction effects of the formulation variables on those physical characteristics and also to optimize the best combination of the variables to formulate small size particles with high encapsulation efficiency. The results showed that all the process variables (amount of polycaprolactone and stirring speed) except the amount of surfactant contributed significantly to the parameters previously mentioned. The best optimized formulation was experimentally validated for the closeness to the theoretical estimates.