Characterisation of indomethacin and nifedipine using variable-temperature solid-state NMR

Apperley, David C.; Forster, Angus H.; Fournier, Romain; Harris, Robin K.; Hodgkinson, Paul; Lancaster, Robert W.; Rades, Thomas

Abstract

We have characterised the stable polymorphic forms of two drug molecules, indomethacin (1) and nifedipine (2) by C-13 CPMAS NMR and the resonances have been assigned. The signal for the C-Cl carbon of indomethacin has been studied as a function of applied magnetic field, and the observed bandshapes have been simulated. Variable-temperature H-1 relaxation measurements of static samples have revealed a T-1 rho minimum for indomethacin at 17.8 degrees C. The associated activation energy is 38 kJ mol(-1). The relevant motion is probably an internal rotation and it is suggested that this involves the C-OCH3 group. Since the two drug compounds are potential candidates for formulation in the amorphous state, we have examined quench-cooled melts in detail by variable-temperature C-13 and H-1 NMR. There is a change in slope for TH1H at the glass transition temperature (T-g) for indomethacin, but this occurs a few degrees below Tg for and T-1 rho(H) nifedipine, which is perhaps relevant to the lower real-time stability of the amorphous form for the latter compound. Comparison of relaxation time data for the crystalline and amorphous forms of each compound reveals a greater difference for nifedipine than for indomethacin, which again probably relates to real-time stabilities. Recrystallisation of the two drugs has been followed by proton bandshape measurements at higher temperatures. It is shown that, under the conditions of the experiments, recrystallisation of nifedipine can be detected already at 70 degrees C, whereas this does not occur until 110 degrees C for indomethacin. The effect of crushing the amorphous samples has been studied by C-12 NMR; nifedipine recrystallises but indomethacin does not. The results were supported by DSC, powder XRD, FTIR and solution-state NMR measurements. Copyright (c) 2005 John Wiley & Sons, Ltd.

Citation

Apperley, D. C., Forster, A. H., Fournier, R., Harris, R. K., Hodgkinson, P., Lancaster, R. W., & Rades, T. (2005). Characterisation of indomethacin and nifedipine using variable-temperature solid-state NMR. Magnetic Resonance in Chemistry, 43(11), 881-892. https://doi.org/10.1002/mrc.1643

• Journal Article Type: Article
• Publication Date: 2005-11
• Journal: Magnetic Resonance in Chemistry
• Print ISSN: 0749-1581
• Electronic ISSN: 1097-458X
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 43
• Issue: 11
• Pages: 881-892
• DOI: https://doi.org/10.1002/mrc.1643
• Public URL: https://durham-repository.worktribe.com/output/1572062