研制及特性分析格列美脲纳米晶体配方及其在大鼠体内的药代动力学评价。
Development and characterization of glimepiride nanocrystal formulation and evaluation of its pharmacokinetic in rats.
机构信息
School of Pharmaceutical Sciences, Jilin University, Changchun, China.
出版信息
Drug Deliv. 2013;20(1):25-33. doi: 10.3109/10717544.2012.742939.
In this paper, orally nanocrystal capsules were produced using nanocrystal formulations in order to optimize dissolution properties of poorly soluble drug glimepiride and improve its bioavailability. The important preparation variables, such as stabilizers, the power input and the time length of ultrasonication on the mean particle size and polydispersity index were investigated systematically, and the optimal values were 0.2% glimepiride (w/v), 1.2% Lipoid S100, 0.6% PEG 6000 (w/v), 0.6% PVPK 30 (w/v), 500 W and 2 min, respectively. Characterization of glimepiride nanocrystal was carried out by X-ray powder diffractometry, differential scanning calorimetry and scanning electron microscopy. In vitro dissolution test, the nanocrystal-loaded capsules of glimepiride showed an evident increase in dissolution rate compared to micronized and market capsules. The in vivo studies demonstrated that a marked enhancement of bioavailability of nanocrystal-loaded capsules was superior compared to the marketed formulation and microcrystal-loaded capsules, which may reduce the risk of side effect by allowing a reduction in either the dose or its frequency of administration.
本文采用纳米晶体制剂制备口服纳米晶胶囊，以优化难溶性药物格列美脲的溶解性能，提高其生物利用度。系统研究了稳定剂、功率输入和超声时间等重要制备变量对平均粒径和多分散指数的影响，优化条件分别为：格列美脲（w/v）0.2%、Lipoid S100 1.2%、PEG 6000（w/v）0.6%、PVPK 30（w/v）0.6%、500 W 和 2 min。采用 X 射线粉末衍射法、差示扫描量热法和扫描电子显微镜对格列美脲纳米晶进行了表征。体外溶出试验结果表明，与微粉化胶囊和市售胶囊相比，载格列美脲纳米晶胶囊的溶出速率明显提高。体内研究表明，与市售制剂和载微晶胶囊相比，载纳米晶胶囊的生物利用度显著提高，这可能通过降低剂量或减少给药频率降低副作用风险。
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