Methods to control the particle sizes of active pharmaceutical ingredients were investigated using sodium ecabet (NaECA) hydrate, which tends to generate large plate-like crystals, as a model compound. In batch-cooling crystallization in H2O, the particle size decreased as the cooling rate was increased. Although the particle size reached 97 mu m at a cooling rate of 40 degrees C/h, this may be too large for formulation without further physical processing. A series of semi-batch crystallization experiments was conducted by adding aqueous Na-ECA solution to aqueous NaCl. In these experiments, the particle sizes decreased to less than 7 mu m as the NaCl concentration was increased to > 1.2% w/w. The particles yielded by semi-batch crystallization showed improved particle size distributions compared to those obtained by the batchcooling crystallization method. The solubility of Na-ECA hydrate decreased to less than 10% of that in pure water as the NaCl concentration was increased to 3.0% w/w. This solubility change enabled the production of a highly supersaturated environment, allowing facile generation of microcrystals with a narrow particle size distribution.