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KMID : 0043320100330010095
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Archives of Pharmacal Research
2010 Volume.33 No. 1 p.95 ~ p.101
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Enhanced Oral Bioavailability of Flurbiprofen by Combined Use of Micelle Solution and Inclusion Compound
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Choi Han-Gon
Li Dong-Xun
Oh Dong-Hoon
Yong Chul-Soon
Kim Jong-Oh
Seo Youn-Gee
Han Myo-Jeong
Balakrishnan Prabagar
Yan Yi-Dong
Joe Jung-Hyun
Park Sang-Man
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Abstract
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The main purpose of this study was to evaluate the effect of a mixed drug solution containing a surfactant and β-cyclodextrin (β-CD) on the solubility and bioavailability of a poorly watersoluble drug, flurbiprofen. Solubility, dissolution and in vivo pharmacokinetics of flurbiprofen in the presence of surfactant, β-CD or mixture of surfactant and β-CD were investigated. Among the surfactants tested, Tween 80 produced the highest improvement in the aqueous solubility of flurbiprofen. The solubility of flurbiprofen increased linearly as a function of β-CD, resulting in B8 type that suggested a formation of inclusion complex in a molar ratio of 1:1. The solubility of flurbiprofen increased further when Tween 80 was included in addition to β-CD, suggesting that a micelle formation in the presence of Tween 80 was the likely reason for additional increase. Furthermore, the data suggested that Tween 80 did not interfere with the inclusion interaction between flurbiprofen and β-CD. The solubility of flurbiprofen was the highest in the mixed system containing 1.3 mM β-CD and 0.3% w/v Tween 80, and the maximum solubility of 160 μg/mL was achieved. Consistent with the enhanced solubility, the plasma exposure (both AUC and Cmax) of flurbiprofen when dosed as the mixed system was significantly higher (as much as 2 to 3-fold) than that without surfactant or β-CD, with surfactant alone, or with β-CD alone. Therefore, the mixed system consists of surfactant and β-CD could be used as an effective oral dosage form to improve bioavailability of poorly water soluble drugs such as flurbiprofen.
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KEYWORD
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Tween 80, β-cyclodextrin, Flurbiprofen, Solubility, Bioavailability
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