New solid modifications of nateglinide

New modifications of the antidiabetic drug nateglinide were found and characterized by means of thermal analysis, vibrational spectroscopy and X-ray powder diffractometry. In particular it has been verified that the product obtained during the final steps of the nateglinide synthesis is the hemihydrate form which melts at about 86 °C provided that the adopted experimental conditions hinder the removal of the crystallization water. Otherwise, if the crystallization water is removed, the hemihydrate transforms to a new anhydrous polymorph that melts at 102.8 °C. The anhydrous polymorph, if stored at room temperature and humidity, gradually changes to H polymorph while, if stored in water vapour saturated atmosphere, it gets back water and reverts to the hemihydrate form. On the contrary, both an isothermal treatment at 80 °C and melt cooling bring to the B polymorph.