A. C. Schmidt
Aug 12, 2005
Citations
0
Influential Citations
16
Citations
Journal
Journal of Thermal Analysis and Calorimetry
Abstract
SummaryChloroprocaine hydrochloride (2-CPCHC) is a local anaesthetic agent of the ester type preferentially used for epidural anaesthesia. The compound, official in the USP, was found to exist in two polymorphic crystal forms which have been characterized by thermomicroscopy, differential scanning calorimetry (DSC), pycnometry, FTIR-, FT-Raman-spectroscopy as well as X-ray powder diffractometry. Based on these data the relative thermodynamic stability of the two forms was determined and is represented in a semi-schematic energy/temperature diagram. Mod. I° is the thermodynamically stable form at room temperature. This form is present in commercial products and can be crystallized from ethanol. Mod. II can be obtained by annealing the supercooled melt in a temperature range between 100 and 130°C. Upon heating mod. II exhibits an exothermic phase transition (ΔtrsHII-I: -5.0±0.5 kJ mol-1) at about 134°C to mod. I° (melting point 175°C, ΔfusHI: 46.6±0.6 kJ mol-1). The exothermic transformation of mod. II to mod. I° confirms that mod. I° is thermodynamically stable in the entire temperature range (heat of transition rule) whereas mod. II is monotropically related to mod. I°, i.e. is metastable at all temperatures below its melting point. Mod. II is of low kinetic stability at room temperature and the transformation to mod. I° starts within a few minutes at room temperature. The N-H band in the infrared spectrum of mod. I° (3433 cm-1) lies at significantly higher wavenumbers than that of mod. II (3413 cm-1) indicating differences in the hydrogen bonding arrangement. Furthermore, the measured density of mod. I° is lower than the density of mod. II and thus both, the IR- and the density-rule are violated in this polymorphic system.