Miscibility of Nifedipine and Hydrophilic Polymers as Measured by ^1H-NMR Spin-Lattice Relaxation
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概要
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The miscibility of a drug with excipients in solid dispersions is considered to be one of the most important factors for preparation of stable amorphous solid dispersions. The purpose of the present study was to elucidate the feasibility of ^1H-NMR spin-lattice relaxation measurements to assess the miscibility of a drug with excipients. Solid dispersions of nifedipine with the hydrophilic polymers poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose (HPMC) and α,β-poly(N-5-hydroxypentyl)-L-aspartamide (PHPA) with various weight ratios were prepared by spray drying, and the spin-lattice relaxation decay of the solid dispersions in a laboratory frame (T_1 decay) and in a rotating frame (T_<1ρ> decay) were measured. T_<1ρ> decay of nifedipine-PVP solid dispersions (3:7, 5:5 and 7:3) was describable with a mono-exponential equation, whereas T_<1ρ> decay of nifedipine-PHPA solid dispersions (3:7, 4:6 and 5:5) was describable with a bi-exponential equation. Because a mono-exponential T_<1ρ> decay indicates that the domain sizes of nifedipine and polymer in solid dispersion are less than several nm, it is speculated that nifedipine is miscible with PVP but not miscible with PHPA. All the nifedipine-PVP solid dispersions studied showed a single glass transition temperature (T_g), whereas two glass transitions were observed for the nifedipine-PHPA solid dispersion (3:7), thus supporting the above speculation. For nifedipine-HPMC solid dispersions (3:7 and 5:5), the miscibility of nifedipine and HPMC could not be determined by DSC measurements due to the lack of obviously evident T_g. In contrast, ^1H-NMR spin-lattice relaxation measurements showed that nifedipine and HPMC are miscible, since T_<1ρ> decay of the solid dispersions (3:7, 5:5 and 7:3) was describable with a mono-exponential equation. These results indicate that ^1H-NMR spin-lattice relaxation measurements are useful for assessing the miscibility of a drug and an excipient in solid dispersions.
- 公益社団法人日本薬学会の論文
- 2007-08-01
著者
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Kawanishi Tohru
National Institute Of Health Sciences
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MURANUSHI NORIYUKI
Shionogi Research Laboratories, Shionogi & Co., Ltd.
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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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Kitamura Satoshi
Astellas Pharma Inc.
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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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TANAKA Kazuyuki
Astellas Pharma Inc.
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TAKAKURA Asako
Shionogi & Co., Ltd.
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HAYASHI Takashi
Shionogi & Co., Ltd.
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Takakura Asako
Shionogi & Co. Ltd.
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Muranushi Noriyuki
Shionogi & Co. Ltd.
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Hayashi Takashi
Shionogi & Co. Ltd.
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