Lamprecht Alf, Yamamoto Hiromitsu, Takeuchi Hirofumi, Kawashima Yoshiaki
Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 5-6-1 Mitahora Higashi, 502-8585 Gifu, Japan.
J Control Release. 2003 Jul 31;90(3):313-22. doi: 10.1016/s0168-3659(03)00195-0.
The treatment of colon cancer has been aimed by approaches of oral drug administration. 5-Fluorouracil is the standard treatment still nowadays and would be a candidate to be delivered orally to the colon. A pH-sensitive polymer Eudragit P-4135F was used to prepare microspheres by a simple oil/water emulsification process. Process parameters were analyzed in order to optimize the drug loading and release profiles. In further attempts mixtures with Eudragit RS100 were prepared to prolong drug release. Scanning electron microscopy and confocal laser scanning microscopy permitted a structural analysis. The solvent extraction was preferable over solvent evaporation with a view to the encapsulation rate (extraction: 37%; evaporation: 19%) due to the hydrophilic character of the drug while release pattern were nearly unchanged. Eudragit P-4135F, pure or in mixture, was found to retain drug release at pH 6.8 lower than 35% within 6 h. At pH 7.4, nearly immediate release (within 30 min) was observed for pure P-4135F, while mixtures enabled to prolong the release slightly. Analysis of the morphology led to an inhomogeneous polymer distribution of P-4135F and RS100 throughout the particle core. A capsule-like structure was concluded which allowed only slight changes of the release kinetics by the addition of RS100. However, the formulation proved its applicability in-vitro as a promising device for pH-dependent colon delivery of 5-fluorouracil.
结肠癌的治疗一直以口服给药方式为目标。5-氟尿嘧啶至今仍是标准治疗药物，有望制成口服结肠给药制剂。采用pH敏感聚合物Eudragit P-4135F，通过简单的油/水乳化工艺制备微球。分析工艺参数以优化载药率和释放曲线。进一步尝试制备了与Eudragit RS100的混合物以延长药物释放。通过扫描电子显微镜和共聚焦激光扫描显微镜进行结构分析。鉴于药物的亲水性，就包封率而言（萃取法：37%；蒸发法：19%），溶剂萃取法优于溶剂蒸发法，而释放模式几乎没有变化。发现Eudragit P-4135F纯品或其混合物在pH 6.8时6小时内药物释放率低于35%。在pH 7.4时，观察到纯P-4135F几乎立即释放（30分钟内），而混合物能使释放稍有延长。形态分析表明P-4135F和RS100在整个颗粒核心内聚合物分布不均匀。得出存在胶囊样结构的结论，即加入RS100只会使释放动力学稍有变化。然而，该制剂在体外证明了其作为5-氟尿嘧啶pH依赖型结肠给药的有前景装置的适用性。
