Background:Domperidone (DOM), a dopamine receptor antagonist, is used as antiemetic for the treatment of gastroparesis, vomiting, and nausea. The low water solubility of DOM leads to a low dissolution rate and variable bioavailability. The aim of this study was to enhance the solubility of DOM by the preparation of micron-sized particles.Materials and Methods:The in situ micronization process was carried out using solvent change method in the presence of Soluplus® or PEG6000 as stabilizing agents. DOM was dissolved in appropriate solvent (acetone and methanol 1:1 v/v), and the stabilizing agent was dissolved in water (as nonsolvent). The nonsolvent was poured rapidly into the drug solution under stirring by a homogenizer, and the resultant was freeze dried. The crystalline shape and particle size of DOM and interaction of DOM with stabilizers were investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC), and then, dissolution test was carried out.Results:Optimum formulation was composed of DOM (0.5%) and PEG6000 (0.1%) with the lowest particle size (3 μm) and the highest DE60% (95.95%) as compared to pure DOM (particle size of 13.4 μm and DE60% 52.18%).Conclusion:SEM micrographs showed uniform and spherical shape of microcrystals. FTIR, XRD, and DSC studies indicated the micron size of the microcrystals and no interference between the drug and the stabilizer.