Mechanochemical Solid-State Polymerization (XI) : Effect of Water-Insoluble Pharmaceutical Aids on Drug Release from Mechanically Synthesized Polymeric Prodrugs
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概要
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We discuss here the effect of water-insoluble pharmaceutical aids on the nature of drug release from composite polymeric prodrugs synthesized by mechanochemical solid-state polymerization. Magnesium stearate (Mgst) and hydrogen castor oil (HCO) were used as water-insoluble pharmaceutical aids. Composite polymeric prodrugs were synthesized by the mechanochemical solid-state polymerization of a vinyl monomer of 5-fluorouracil (I) in the presence of Mgst or HCO. The molecular weight of the resulting polymeric prodrugs increased with increasing the content of Mgst or HCO. Prodrug hydrolysis was carried out in a heterogeneous system in phosphate buffer at pH 6.8 and 37℃. The rate of drug release from the composite polymeric prodrug containing Mgst (Poly-Mgst) was faster than that from polymeric prodrug containing no pharmaceutical aids (Poly-Non), while hydrolysis of the composite polymeric prodrug containing HCO (Poly-HCO) was slower than Poly-Non. Scanning electron microscope (SEM) photos showed the surface of Poly-HCO was smoother than that of Poly-Non and Poly-Mgst. It was suggested that the slower drug release from Poly-HCO may be responsible for the smaller specific surface area than that of Poly-Non. It was also shown that the rate of drug release from the composite polymeric prodrugs decreases with increasing the content of Mgst or HCO. Hence, novel composite polymeric prodrugs with a variety of drug release rates can be prepared by mechanochemical solid-state polymerization in a totally dry process.
- 公益社団法人日本薬学会の論文
- 2004-11-01
著者
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葛谷 昌之
Matsuyama Univ. Ehime Jpn
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Kondo S
Hoechst Japan Co. Ltd.
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近藤 修二
Hoechst Japan Co. Ltd.
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Kondo Shigemi
Nissui Pharmaceutical Co. Ltd.
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KONDO Shin-ichi
Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical University
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SASAI Yasushi
Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical University
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笹井 泰志
岐阜薬科大学
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KUZUYA Masayuki
Laboratory of Pharmaceutical Physical Chemistry, Gifit Pharmaceutical University
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HOSAKA Shouichi
Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical University
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Hosaka Shouichi
Laboratory Of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University
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Kondo S
Ntt Photonics Laboratories
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Kondo S
Kyoritsu Coll. Pharmacy Tokyo Jpn
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Kondo Shin-ichi
Dep. Of Pharmaceutical Physical Chemistry Gifu Pharmaceutical Univ.
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Kuzuya Masayuki
Laboratory Of Pharmaceutical Physical Chemistry Gifu Pharmaceutical University
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Sasai Yasushi
Gifu Pharmaceutical Univ. Gifu Jpn
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近藤 伸一
岐阜薬科大学
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Kondo Shin-ichi
Laboratory of Pharmaceutical Physical Chemistry, Department of Drug Delivery Technology and Science, Gifu Pharmaceutical University
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