Effect of Preparation Temperature in Solvent Evaporation Process on Eudragit RS Microsphere Properties

Eudragit RS 100 microspheres containing ketoprofen as a model drug were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The influence of various preparation temperatures : 10, 25, 35, and 40 ℃, on particle size and morphology, drug content and release kinetics, and drug crystal state was evaluated. With increasing temperature, microsphere average size was found to increase and particle size distribution to widen significantly. At 10 ℃ particles of irregular shape are formed, whereas higher temperatures gradually improve the sphericity of microspheres. As can be seen from SEM photographs, particle surface roughness decreases as preparation temperature increases. It was found that temperature had no effect either on ketoprofen microencapsulation efficiency or on its crystal state, but it does influence emulsion-stabilizer incorporation. Ketoprofen forms solid solution in Eudragit matrix and maintains amorphous state for significant period of time. Drug release rates from microspheres correlated with microspheres' surface roughness and to a lesser extent with particle size.