Microspheres of salbutamol sulphate (SS) with poly(lactic acid-co-glycolic acid) (PLGA 85115) were prepared by the modified solvent evaporation method using a double emulsion. In the preparation of the formulations, we used a 2(3) factorial design based on three independent variables: drug loading, amount of gelatin and concentration of PVA. The dependent variables are particle size of the microspheres and entrapment ratio % in the microspheres. The effect of the three independent variables on the particle size and entrapment ratio % were evaluated with analysis of variance and response surface graphs. The in vitro release studies were carried out by shaking in isotonic phosphate buffer solution: pH 7.4. The particle sizes of microspheres were determined by infrared particle size apparatus (IPS). The interaction between PLGA and drug was investigated by DSC and FT-IR analysis. Extended release was obtained for 96 h with F8 formulation microspheres. The best release profile (F8 formulation) fitted the dissolution model proposed by Baker and Lonsdale. In vitro degradation of the best formulation was investigated using scanning electron microscopy. The pore size increased with time and then degraded becoming empty holes.