PURPOSE: The purpose of the current study was to evaluate the molecular mobility of amorphous indomethacin and salicin in the relaxed glassy state based on spin-lattice relaxation times (T(1c)) and to clarify the effects of molecular mobility on their physical stability. METHODS: Pulverized glassy amorphous indomethacin and salicin samples were completely relaxed, and the T(1c) values were investigated using solid-state (13)C-nuclear magnetic resonance (NMR) at temperatures below the glass transition temperature (T(g)). All NMR spectra were obtained using the T(1c) measurement method combined with variable-amplitude cross-polarization, the Torchia method, and total sideband suppression method. RESULTS: The T(1c) value of amorphous indomethacin indicated that 73% of carbons were in a state of monodispersive relaxation, suggesting that the amorphous state was relatively homogeneous and restricted, particularly in backbone carbons. On the other hand, 92% of carbons of amorphous salicin exhibited both fast and slow biphasic relaxation. Individual structures of the salicin molecules behaved heterogeneously, and thus the entire molecule showed relatively fast local as well as slow mobility. CONCLUSIONS: At temperatures below T(g), amorphous salicin had relatively greater molecular mobility than amorphous indomethacin. This difference in the molecular mobility of the two compounds is correlated with their crystallization behavior. Solid-state (13)C NMR provides valuable information on the physical stability of amorphous pharmaceuticals.
PURPOSE: The purpose of the current study was to evaluate the molecular mobility of amorphous indomethacin and salicin in the relaxed glassy state based on spin-lattice relaxation times (T(1c)) and to clarify the effects of molecular mobility on their physical stability. METHODS: Pulverized glassy amorphous indomethacin and salicin samples were completely relaxed, and the T(1c) values were investigated using solid-state (13)C-nuclear magnetic resonance (NMR) at temperatures below the glass transition temperature (T(g)). All NMR spectra were obtained using the T(1c) measurement method combined with variable-amplitude cross-polarization, the Torchia method, and total sideband suppression method. RESULTS: The T(1c) value of amorphous indomethacin indicated that 73% of carbons were in a state of monodispersive relaxation, suggesting that the amorphous state was relatively homogeneous and restricted, particularly in backbone carbons. On the other hand, 92% of carbons of amorphous salicin exhibited both fast and slow biphasic relaxation. Individual structures of the salicin molecules behaved heterogeneously, and thus the entire molecule showed relatively fast local as well as slow mobility. CONCLUSIONS: At temperatures below T(g), amorphous salicin had relatively greater molecular mobility than amorphous indomethacin. This difference in the molecular mobility of the two compounds is correlated with their crystallization behavior. Solid-state (13)C NMR provides valuable information on the physical stability of amorphous pharmaceuticals.
Authors: Subhasish Chatterjee; Antonio J Matas; Tal Isaacson; Cindie Kehlet; Jocelyn K C Rose; Ruth E Stark Journal: Biomacromolecules Date: 2015-12-24 Impact factor: 6.988
Authors: Simon Bates; George Zografi; David Engers; Kenneth Morris; Kieran Crowley; Ann Newman Journal: Pharm Res Date: 2006-09-22 Impact factor: 4.200
Authors: N M Belozerova; P Bilski; M Jarek; J Jenczyk; S E Kichanov; D P Kozlenko; J Mielcarek; A Pajzderska; J Wąsicki Journal: RSC Adv Date: 2020-09-11 Impact factor: 3.361