Conformational polymorphs of a muscle relaxant, metaxalone

Abstract

Metaxalone (MTX) is a muscle relaxant which is used to relieve pain caused by strains and sprains. MTX has been in the market under the brand name of Skelaxin since 1962, and two polymorphs of MTX were first mentioned in a patent published in 2007. However, their crystal structures, stability relationship, and dissolution profiles have not yet been analyzed. We herein report two conformational polymorphs of racemic MTX with an objective to unravel the structural origin of polymorphism and study their phase transformations, stability, solubility, and dissolution properties. Both forms were obtained concomitantly by cooling crystallization experiments from ethyl acetate. Crystal structure analysis revealed that the MTX molecule adopts different conformations in the polymorphs. Interestingly, the imide group of the MTX forms an imide-imide catemer synthon in Form A and an imide-imide dimer synthon in Form B. Thermal analysis and solubility measurements suggest an enantiotropic relationship between the polymorphs with Form B being the thermodynamically stable form at ambient conditions. The metastable Form A converts to stable Form B in slurry and solid-state grinding experiments and dissolves faster than the stable Form B at 37 °C. © 2011 American Chemical Society.