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Microspheres containing theophylline (TH) were prepared from a hydrophobic dextran derivative by emulsion solvent evaporation method. The objective of this study was to evaluate the effects of poor solvent in dispersed phase on the particle properties and drug release characteristics of the microspheres. Mixtures of acetone and water were used as the dispersed phase and liquid paraffin as the continuous phase. The amount of water (poor solvent for polymer) was varied from 0.5 to 2 ml in 15 ml of dispersed phase. Drug release from the microspheres was examined using JPXIV 1st Fluid (pH 1.2) containing 0.02% Tween 20, and their structure was analyzed by scanning electron microscopy (SEM). The drug release behaviors were greatly affected by the amount of water. The percentage released until 8 h were 89% and 23% for 0.5 and 2.0 ml of water, respectively. The release mechanism shifted from Fickian diffusion to zero-order transport as the amount of water increased. According to SEM observations, TH was uniformly distributed over the entire microsphere prepared using 0.5 ml of water, and existed in the center of the microsphere, having a core-shell structure, when prepared using 2 ml of water. The amount of poor solvent in the dispersed phase was found to be a crucial factor determining the internal structure of microspheres and drug release characteristics.

Effect of Amount of Water in Dispersed Phase on Drug Release Characteristics of Dextran Microspheres Prepared by Emulsion-Solvent Evaporation Process