Polymorphism in metoclopramide hydrochloride and metoclopramide

Metoclopramide hydrochloride (MCPHCl.H2O) and metoclopramide base (MCP) have been studied by DSC, thermomicroscopy, X-ray diffraction and infrared spectroscopy. MCPHCl.H2O does not readily lose water of crystallization either from the solid state or from the melt, but depending on the conditions, dehydration can give rise to two anhydrous polymorphs, MCPHCl/Form I (mp 187 degrees C) and MCPHCL/Form II (mp 155 degrees C). Form I crystallizes from the melt of Form II and not by a reversible solid-solid transition. The anhydrous hydrochloride therefore shows monotropic polymorphism where Form I is the stable polymorph and Form II, a metastable polymorph. Thermal analysis of MCP shows that the base exists as two enantiotropic polymorphs. The transition of the form stable at room temperature (MCP/Form I) to the form stable at high temperatures (MCP/Form II mp 147 degrees C) occurs extremely rapidly at 125 degrees C but the reverse process requires one month at room temperature (approximately equal to 22 degrees C). It is therefore possible to compare the X-ray diffraction powder patterns and infrared spectra of MCP Forms I and II.