Laponite, a form of layered aluminosilicates, and itraconazole, a water insoluble drug, were hybridized through an interfacial reaction at the boundary between water and a water-immiscible liquid. The reaction was carried out under a controlled pH to maintain both physical and chemical stability of the drug. The X-ray diffraction patterns and spectroscopic analyses indicated that itraconazole was intercalated into the interlayer space of clay with a lateral monolayer structure. No significant chemical structural change of itraconazole was seen through the formation of the hybrid. The hybrid system exhibited enhanced solubility and controlled release of itraconazole. The released amount of itraconazole could be controlled in the range from 18 to 75%, depending on the kinds of cations in the release media.