Prednisolone acetate (PA)-loaded microspheres were prepared by the spray-drying technique using different polymer (1% and 2%) and drug concentrations (10% and 20%). To obtain the optimum formulation, a three-factor two-level (2(3)) design was employed. The independent variables were polymer molecular weight, polymer concentration, and theoretical drug loading. Responses were the particle size, percentage of encapsulation efficiency, and the t(50%) release. The best formulation was prepared with 20% of PA and 1% of chitosan with medium molecular weight showing relative good yield of production (48.0 + or - 6.7%) and encapsulation efficiency (45.7 + or - 0.3%), and released the drug at a constant rate in 11 days.