Solid-state characterization of falicaine hydrochloride and isomorphic dyclonine hydrochloride

Two homologous local anaesthetic drugs, falicaine (propipocaine) hydrochloride (1-(4-propoxyphenyl)-3-(1-piperidinyl)-1-propanone hydrochloride, PPCHC) and dyclonine hydrochloride (1-(4-butoxyphenyl)-3-(1-piperidinyl)-1-propanone hydrochloride, DCNHC) were characterized by thermal analysis (hot-stage-microscopy, differential scanning calorimetry, thermogravimetry), vibrational spectroscopic methods (FTIR-, FT-Raman-spectroscopy), powder X-ray diffractometry, solid-state-/solution-NMR and water-vapor sorption analysis. The formation and thermodynamic stability of the two different solid phases of both the compounds is described and presented in a flow chart and energy/temperature-diagram, respectively. Of the two substances investigated, mod. II° is the thermodynamically stable form at room temperature. This form is present in commercial products of PPCHC as well as of DCNHC, and it endothermally transforms to the less stable form mod. I, at about 10 K prior to the melting points. The stable mod. II° crystallizes from all tested solvents. Mod. I crystallizes from the super cooled melt. According to the heat of transition rule, mod. I is the thermodynamically less stable form below the transition temperature (enantiotropism). The transition temperatures as well as the melting points of the stable forms could be experimentally determined. The sorption isotherms show a distinct higher hygroscopicity for the less stable mod. I of PPCHC and DCNHC. Solid-state NMR spectra were used to obtain both structural- and molecular-level mobility information.