Investigation of polymorphism of mexiletine hydrochloride by Fourier transform infrared and differential scanning calorimetric techniques

Abstract

Six modified forms of mexiletine [1-methyl-2-(2,6-dimethylphenoxy)ethylamine] hydrochloride were identified and compared by Fourier transform infrared (FTIR) and differential scanning calorimetric (DSC) techniques. Three of these forms have not previously been described. A Euclidean (least squares) algorithm was used for calculating the hit quality indices (HQI). An HQI near 0.0 (⩽0.1) indicates that a very small difference exists between two spectra. A higher HQI indicates a diminishing likelihood that they are the same. A wavenumber range from 2100 to 400 cm^–1 was used. At higher wavenumbers the reproducibility was poorer because of the absorption of νOH, ν_as CO₂ and νNH, which were influenced by a variety of effects. An HQI matrix was constructed and the elements of it clearly demonstrated the degree of identity or divergence with regard to each pair of modified crystalline forms. Two peaks appeared in thermograms of forms I–V. Peaks at lower temperatures (122–162 °C) belonged to crystalline transitions, and those at higher temperatures (202 °C) belonged to the melting of form VI obtained after transition. The FTIR and DSC results showed that both complicated relationships between the polymorphs and kinetically and thermodynamically controlled transformations into other forms can occur during storing and handling of samples.