Solid Dispersions of Benidipine Hydrochloride. II. Investigation of the Interactions among Drug, Polymer and Solvent in Preparations
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概要
- 論文の詳細を見る
The solubilization mechanism of benidipine hydrochloride in two kinds of organic solvent systems has been investigated : one in an organic solution of Eudragit^<[○!R]> E-100 (OSE), and the other in binary solvent mixtures (BSM) of alchol-cosolvent. In the OSE, the organic solubility of the drug was increased in proportion to the polymer concentration. Fourier transform infrared spectroscopy clearly demonstrated the existence of hydrogen bonds between dimethylamino groups of the polymer and piperidine NH^+ of the drug. The ultraviolet absorption maximum of the drug in the 350 nm region blue-shifted in dichloromethane or chloroform with polymer, whereas this shift was not found in ethanol or acetonitrile with the polymer. In the BSM, the logarithmic maximum solubility of the drug in ethanol-cosolvent mixtures was linearly related to the π^* (dipolarity-polarizability) value of the cosolvent. The initial slope of the drug solubility curve in alcohol-dichloromethane mixtures was in good correlation with the α (hydrogen-bond donor acidity) value alcohol. Therefore, it was understood that the solubilization of benidipine hydrochloride in the OSE resulted form the drug-polymer complexation with the intermolecular hydrogen bonding and dipolar interactions, and the solubilization effect in the BSM arose from the enhancement of the proton donor ability of alcohol molecules by the dipolar interactions with the cosolvent.
- 公益社団法人日本薬学会の論文
- 1996-02-15
著者
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鈴木 秀行
原町赤十字病院 内科
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Suzuki Hideshi
Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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MIYAMOTO Norifumi
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.,
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MASADA Tomoaki
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.,
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HAYAKAWA Eiji
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.,
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ITO Kunio
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.,
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Itoh K
Drug Formulation Research Laboratories Phaemaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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Ito Kunio
Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Suzuki H
Showa College Of Pharmaceutical Sciences
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Suzuki H
Janssen Pharmaceutical K.k. Shizuoka Jpn
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Hayakawa E
Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd
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Hayakawa Eiji
Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Miyamoto Naoki
Medicinal Chemistry Research Laboratries Pharmaceutical Research Division Takeda Chemical Industries
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Masada T
Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Ito K
Janssen Pharmaceutical K.k. Shizuoka Jpn
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Hayakawa Eiji
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., LTD
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