Variable Temperature Studies of a Polymorphic System Comprising Two Pairs of Enantiotropically Related Forms:  [S,S]-Ethambutol Dihydrochloride

Of the four known polymorphs of [S,S]-ethambutol dihydrochloride, two transform in an enantiotropic single-crystal-to-single-crystal phase transformation from Form II to Form I on heating. The crystal structures of these two forms have been solved and compared. Because the other two forms are metastable and are only obtained from the melt, single-crystal data could not be obtained on them. However, all four forms have been characterized, and their relative thermodynamic relationships have been investigated by variable-temperature solid-state 13C NMR, variable-temperature powder X-ray diffraction studies, differential scanning calorimetry, and optical microscopy.