Feasibility of ^<19>F-NMR for Assessing the Molecular Mobility of Flufenamic Acid in Solid Dispersions
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概要
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The purpose of the present study was to clarify the feasibility of ^<19>F-NMR for assessing the molecular mobility of flufenamic acid (FLF) in solid dispersions. Amorphous solid dispersions of FLF containing poly-(vinylpyrrolidone) (PVP) or hydroxypropylmethylcellulose (HPMC) were prepared by melting and rapid cooling. Spin-lattice relaxation times (T_1 and T_<1ρ>) of FLF fluorine atoms in the solid dispersions were determined at various temperatures (-20 to 150℃). Correlation time (τ_c), which is a measure of rotational molecular mobility, was calculated from the observed T_1 or T_<1ρ> value and that of the T_1 or T_<1ρ> minimum, assuming that the relaxation mechanism of spin-lattice relaxation of FLF fluorine atoms does not change with temperature. The τ_c, value for solid dispersions containing 20% PVP was 2-3 times longer than that for solid dispersions containing 20% HPMC at 50℃, indicating that the molecular mobility of FLF in solid dispersions containing 20% PVP was lower than that in solid dispersions containing 20% HPMC. The amount of amorphous FLF remaining in the solid dispersions stored at 60℃ was successfully estimated by analyzing the solid echo signals of FLF fluorine atoms, and it was possible to follow the overall crystallization of amorphous FLF in the solid dispersions. The solid dispersion containing 20% PVP was more stable than that containing 20% HPMC. The difference in stability between solid dispersions containing PVP and HPMC is considered due to the difference in molecular mobility as determined by τ_c. The molecular mobility determined by ^<19>F-NMR seems to be a useful measure for assessing the stability of drugs containing fluorine atoms in amorphous solid dispersions.
- 公益社団法人日本薬学会の論文
- 2009-01-01
著者
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Kawanishi Toru
National Institute Of Health Sciences
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Kawanishi Tohru
National Institute Of Health Sciences
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MIYAZAKI Tamaki
National Institute of Health Sciences
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YOSHIOKA SUMIE
National institute of Hygienic Sciences
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Yoshioka Sumie
National Institute Of Health Sciences
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ASO Yukio
National Institute of Health Sciences
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