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시클로덱스트린과의 포접에 의한 케토고나졸의 비점막 흡수증가
Enhanced Nasal Absorption of Ketoconazole by Inclusion with Cyclodextrin
박기배 서보연 안홍직 노현구 온윤성 이광표 ( Gee - Bae Park , Bo - youn Seo , Hong - Jik Ann , Hyun - Goo Rho , Yun - Sung Onn , Kwang - Pyo Lee )
UCI I410-ECN-0102-2008-510-000804378

Inclusion complexes of ketoconazole(KT) with α^-, β^- cyclodextrin(CD) and dimethyl-β-cyclodextrin (CD) and dimethyl-β-cyclodextrin(DMβCD) as nasal absorption enhancer were prepared in 1:2 molar ratios by freeze-drying and solvent evaporation methods. In order to compare with the intrinsic absorptivity of KT in the jejunum(J) and the nasal cavity(N), the in situ simultaneous perfusion method was employed. The in situ recirculation study revealed that KT-CD inclusion complexes with the greater stability constant and the faster dissolution rate proportionally increased the absorption of KT in the J and N of rats. The rank order of apparent KT permeability(P_(app) : ㎝/sec × 10^(-5)±S.E.), corrected by surface area of absorption, was 5.10±0.3(N, KT-DMβCD) >4.13±0.4(N, KT-β-CD) >3.52±0.2(N, KT-α-CD) >2.76±0.3(J, KT-DMβCD) >2.61±0.5(J, KT-β-CD) >2.42±0.4(J, KT-α-CD) at pH 4.0. The in crease in permeability of KT-DMβCD inclusion complex was 2.6 folds in the J and 4.5 folds in the N when the perfusing solution was changed from the buffer(pH 4.0) to saline. The absorption rate of KT-DMβCD inclusion complex after nasal administration was more rapid than those of ketoconazole alone and KT-DMβCD inclusion complex after oral administration to rats. In comparision with an oral administration of ketoconazole suspension in corn oil, the relative bioavailability was calculated 137.3% for the oral and 195.0% for nasal KT-DMβCD inclusion complex in rats. The present results suggest that KT-DMβCD inclusion complex may serve as a potential nasal absorption enhancer for the nasal delivery of ketoconazole.

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