Comparison of Molecular Mobility in the Glassy State Between Amorphous Indomethacin and Salicin Based on Spin-Lattice Relaxation Times |
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Authors: | Email author" target="_blank">Katsuhiko?MasudaEmail author Sachio?Tabata Yasuyuki?Sakata Tetsuo?Hayase Etsuo?Yonemochi Katsuhide?Terada |
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Institution: | (1) Department of Pharmaceutics, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan;(2) Discovery Technology Laboratory II, Mitsubishi Pharma Corporation, Aoba-ku, Yokohama, Kanagawa, Japan;(3) Yokohama Laboratory, Mitsubishi Chemical Group Science and Technology Research Center, Inc., Aoba-ku, Yokohama, Kanagawa, Japan;(4) Yokkaichi Laboratory, Mitsubishi Chemical Group Science and Technology Research Center, Inc., Toho-cho, Yokkaichi, Mie, Japan;(5) Pharmaceutical Technology Coordination Department, Mitsubishi Pharma Corporation, Hasaki Kashima, Ibaraki, Japan |
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Abstract: | 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 (T1c) 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 T1c values were investigated using solid-state 13C-nuclear magnetic resonance (NMR) at temperatures below the glass transition temperature (Tg). All NMR spectra were obtained using the T1c measurement method combined with variable-amplitude cross-polarization, the Torchia method, and total sideband suppression method.Results. The T1c 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 Tg, 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 13C NMR provides valuable information on the physical stability of amorphous pharmaceuticals. |
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Keywords: | amorphous indomethacin amorphous salicin molecular mobility solid-state 13C NMR spin-lattice relaxation times (T1c) |
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