摘要
A novel floating osmotic pump controlled release system （FOP） and traditional matrix sustained release tablets （MT） of dipyridamole （DIP） were characterized in terms of pharmacokinetics, drug release, and in vitro-in vivo correlation. In vivo study was performed by a three-crossover study in six beagle dogs relative to the conventional tablet （CT）. A HPLC method for the determination of DIP in the plasma was developed. Cumulative percent of absorption fraction was compared to that of in vitro cumulative release. Both FOP and MT displayed obvious extended release characteristic in vivo while FOP showed a better extended release behavior. The bioavailability of FOP was higher than that of MT and a zero-order release linear correlation of DIP between fraction absorbed in vivo and fraction dissolved in vitro was established for FOP while not for MT. The results indicated the existence of an absorption window in upper part of the GI track of DIP, which meant that floating system could be excellent for the drug delivery. In addition, the in vitro model was a good choice for depicting in vivo absorption and for optimization of the formulation of FOP if it is needed to be bio-equivalent to MT.
本文考察了双嘧达莫凝胶骨架缓释片(MT)和漂浮渗透泵(FOP)两种制剂比格犬体内药物动力学,并作了体内外相关性分析。以双嘧达莫市售普通片为参比制剂设计了三交叉动物体内实验,以高效液相色谱法检测血药浓度。以体内吸收分数与体外累计释放量作比较来评价体内外相关性。结果表明两种缓控释制剂均表现出体内缓释效果,其中FOP缓释效果更好;FOP生物利用度高于MT;体内外相关系FOP优于MT。分析认为双嘧达莫在消化道上端吸收,由此可以认为双嘧达莫制成漂浮制剂有利于口服药物传递;对于FOP来说现用体外释放方法己可反应体内情况,而对于MT体外溶出方法需进一步改进。
