Vibrational Study of Propantheline Bromide Polymorphism

Propantheline or 2-Propanaminium, N-methyl-N-(1-methylethyl)-N-[2-[(9H-xanthen-9-ylcarbonyl)oxy]ethyl]- bromide is a quaternary ammonium synthetic derivate with modulation activity on vagal tone. It is one of the most parasympatholytic active agent with peripheral activity similar to atropine. It reduces the hypersecretion and the ipermotility of the gastro-intestinal apparatus and it has spasmolitic properties. The presence of two known Propanteline bromide polymorphs is reported in literature1,2: the stable form I and the metastable form II. Through multi-analytical approach used by our group in other pholimorphic studies, in the present communication we report the study and characterization of the studied two forms. For the first time micro-Raman spectroscopy and Hot-Stage Raman microscopy (HSRM) studies of Propantheline polymorphs are reported. Raman techniques were useful tools for distinguish and monitor the conversion of polymorphs cause of changing temperature. The spectroscopic reported data, together with those form previous reports, complete the Propantheline bromide polymorphs knowledge. DSC thermograms and X-Ray powder diffraction data, were also collected. Furthermore XRPD patterns of I and II forms were in agreement with Kountourellis data. Some attributions of significant IR and Raman bands were firstly reported. In summary, the IR spectra permitted to identify I and II polymorphs through their typical bands at 1729, 1250-1235, 1171-1157, 1038, 758-746, 713, 630 cm-1 and 1727-1739, 1260, 1166, 1032, 753-744, 709 cm-1, respectively. The polymorphs characterization through Raman spectroscopy permitted to identify specific bands for form I (1267-1255, 1222, 520, 417-402-380, 294, 255 cm-1) and form II (in particular at 1229, 669, 537-530, 397, 295-282 and 185 cm-1).According to L. Borka results1,6, in this study a conversion of II into I form was observed. The conversion occurred above 100°C with a successive fusion of I form. A further heating caused a decomposition phenomenon. The used temperature program started form 35° until 200°C with an heating rate of 2°C/min. To confirm DSC results of form II, Hot-stage measurements were carried out with the same DSC temperature program (2°C/min; 35-200°C temperature range). By this technique, the same results recovered with DSC thermal curves were noticed: a conversion of II into I form was observed and the successively fusion phenomenon was noticed. At 35°C until 80°C, the micro-Raman spectra correspond to form II, while at 90°C and at 160°C the transformation into I and its melting event were occurred, respectively.Moreover, the thermodynamic and spectroscopic behaviour of ground form I was investigated. Propantheline form I was ground at different times (1, 5, 10, 15, 20 minutes) and FT-IR/ATR and DSC measurements were carried out. In addition, a certain amount of recrystallized Propantheline bromide (form I, II) was placed into a compressing machine to obtain Propantheline bromide tablets using different compression forces (2, 4, 8, 10, 12, 16 and 28 KN). Using Raman microscopy, surfaces and inside tablets studies were carried out for verifying the polymorphic transformations. Polymorphic transformations were not been induced.