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FORMATION OF POORLY WATER-SOLUBLE DRUG NANOPARTICLE BY CO-GRINDING WITH CYCLODEXTRINS   :   シクロデキストリン類との混合粉砕による難溶性医薬品のナノ粒子化 

作成者 Wongmekiat, Arpansiree
作成者の別表記 アーパンシリー, ウォンミーキアット
キーワード等 cyclodextrin, pranlukast, co-grinding, moisture condition monopariticle, poorly water-soluble drug, シクロデキストリン, 難溶性医薬品, 混合粉砕, ナノ粒子, 水分量
日本十進分類法 (NDC) 499
内容 学位:千大院医薬博甲第薬2号
抄録:The present study was the investigation of drug nanoparticle formation by co-grinding with cyclodextrin in attempt to improve the solubility and bioavailability of poorly water-soluble pharmaceutical materials. As a model drug, pranlukast hemihydrate (PRK) was used in this study. Pranlukast is a leukotriene antagonist used for the treatment of asthma. Pranlukast exhibits poor aqueous solubility (1.2 μg/ml at 25℃). Powder X-ray diffraction (PXRD) measurement was used to investigate molecular state of drug and CD in the ground mixtures. Nanoparticle formation in the aqueous phase was investigated by particle size analysis and quantitative determination of drug recovered as nanoparticles. Furthermore, the possible mechanism of nanoparticle formation was proposed. Pranlukast was ground with either β-CD anhydrate or β-CD hydrate (10.5H_2O) crystals at a mixing molar ratio of 2:1 (β-CD:PRK). PXRD results indicated that β-CD anhydrate/PRK GM was amorphous after co-grinding, however, the XRD peak of PRK crystals was still observed in case of the β-CD hydrate/PRK GM indicating PRK was in crystalline form even after co-grinding. With regard to the β-CD hydrate/PRK GM, the particle size distribution indicated the existence of very small particles. After sonication, the suspension was found to consist of only particles smaller than 1μm. In contrast, the β-CD anhydrate/PRK GM exhibited poor wettability and gave aggregates floating on the water surface when it was dispersed into water. Quantitative determination of PRK demonstrated that 960f PRK loaded in GM recovered as drug crystalline nanoparticles (mean particle size:192 nm) when the β-CD hydrate/PRK GM was dispersed into water. On the other hand, drug nanoparticles could not be formed when PRK was co-ground with β-CD anhydrate (recovery=1.4%). These results suggested that the water during the co-grinding process affected the formation of nanoparticles.…

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=00022531
フルテキストへのリンク http://mitizane.ll.chiba-u.jp/metadb/up/assist1/Y_K-003.pdf
言語 英語


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cyclodextrin
pranlukast
co-grinding
moisture condition monopariticle
poorly water-soluble drug
シクロデキストリン
難溶性医薬品
混合粉砕
ナノ粒子
水分量