Crystal polymorphism of local anaesthetic drugs

Crystal polymorphs of pramocaine hydrochloride (PRCNC) and pramocaine (PRCN) free base were produced and characterized by means of thermomicroscopy, differential scanning calorimetry (DSC), FTIR- and FT-Raman-spectroscopy as well as X-ray-powder diffractometry. The relative thermodynamic stabilities of all forms were determined and are represented in semi-schematic energy/temperature diagrams. PRCN, which is a viscous liquid at room temperature and insoluble in water, was found to exist in two different crystal forms with the melting points 23.5°C (mod. I°) and 12.5°C (mod. II). The water-soluble PRCNC crystallizes in three different crystal modifications. Mod. II° is the thermodynamically stable form at room temperature and is present in commercial products. This form is obtained by crystallization from solvents and transforms on heating at about 95°C into the high temperature form mod. I which melts at 171.0°C. Both compounds show conformational polymorphism with forms of low kinetic stability. This revised version was published online in July 2006 with corrections to the Cover Date.