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DISSOLUTION IMPROVEMENT OF A WATER-INSOLUBLE DRUG, (±)-4-(4-cyanoanilino)-5, 6-dihydro-7-hydroxy-7H-cyclopenta [d] pyrimidine 

作成者 碓井, 富佐雄
作成者の別表記 USUI, FUSAO
キーワード等 Insoluble drug, solubilizing, RS-8359, 難溶性薬物, 可溶化
日本十進分類法 (NDC) 490
内容 抄録:(±)-4-(4-cyanoanilino)-5, 6-dihydro-7-hydroxy-7H-cyclopenta [d] pyrimidine (hereinafter denoted as RS-8359) is a water-insoluble compound. Its bioavailability is low because of low solubility in water, and dissolution improvement is necessary to improve the bioavailability. In Part I, effects of water-soluble polymers on the precipitation of RS-8359 in supersaturated solutions containing the polymers were investigated. Hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC) and polyvinylpyrrolidone (PVP) were used as water-soluble polymers. It was observed that RS-8359 in supersaturation precipitated after time lag. Small amounts of these polymers in a phosphate buffer solution (pH 6.8) showed inhibitory effects on the precipitation of RS-8359 in supersaturation. In the cases of HPMC and HPC, the time lag increased as the polymer concentration increased. In the case of PVP, however, the time lag was short and did not increased as the polymer concentration increased. All of the polymers decreased precipitation rates of the compound after the time lag, and the most effective concentrations were found to be 0.01mg/ml for HPMC and HPC, and 0.0001mg/ml for PVP in this experimental range. Two kinds of interaction between the polymer and RS-8359 are suggested. That the precipitates contained the polymers suggests the interaction the polymer and surface of RS-8359 crystal. An increase in the solubility of RS-8359 by the polymers suggests the interaction between the polymer and RS-8359 on the molecular level. It is thought that the interaction between the polymer and RS-8359 on the molecular level increased the time lag, and the interaction between the polymer and the surface of RS-8359 crystal decreased the precipitation rate. In Part II, a study on dissolution improvement of RS-8359 was carried out by preparing solid dispersions by the solvent method. Dissolution properties of solid dispersions are usually improved by decreasing the crystallinity of a targ
学位:千大院薬博甲第107号

寄与者 千葉大学大学院薬学研究院
コンテンツの種類 博士論文 Doctoral Thesis
DCMI資源タイプ text
ファイル形式 application/pdf
ハンドルURL http://mitizane.ll.chiba-u.jp/meta-bin/mt-pdetail.cgi?cd=00022543
フルテキストへのリンク http://mitizane.ll.chiba-u.jp/metadb/up/assist1/Y_K-035.pdf
言語 日本語


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Insoluble drug
solubilizing
RS-8359
難溶性薬物
可溶化