Probing amorphous and crystalline pharmaceuticals systems using NMR

Abstract

The Ή and '3C solution-state NMR spectra of the three studied drug molecules (indomethacin, nifedipine and carbamazepine) were fully assigned. This led to the characterisation and assignment of the '3C CPMAS SSNMR spectra of the stable polymorphic forms of these molecules. The signal for the с-СІ carbon of indomethacin has been studied as a function of applied magnetic field, and the observed bandshapes have been simulated. A T(_1)(^H)and T(_1p)(^H) study was undertaken on the crystalline materials, as well as on the quench-cooled amorphous and PVP/drug co-melts. This was done in order to fulfill the aim of this research, i.e. to understand the difference in stability of the amorphous compounds and also to investigate the effect of the presence of PVP on the stability and mobility of the drug. It was shown that, under the conditions of the experiments, amorphous indomethacin did not recrystallise until 110 c, whilst in the case of nifedipine and carbamazepine the recrystallisation occurred at 70 c and 75 c respectively. It was also shown that in the case of the co-melts a transition occurs consistently between 65 c and 85 c for the three materials and this seems to be due to the Tg of the co-melts. The comparison of the T(_1)(^H)and T(_1p)(^H) data for the different states showed that amorphisation increased the mobility of the sample, this being more pronounced for carbamazepine and nifedipine than for indomethacin, and also that the co-melts were more stable and slightly more mobile than the amorphous compounds. The comparison of the relaxation data between the pure compounds showed that amorphous indomethacin was more stable than the other two amorphous drugs as slope changes occurred for the latter at a temperature below Tg, whilst this happens at or around Tg for amorphous indomethacin.