Curcio Claudia, Greco Antonio S, Rizzo Salvatore, Saitta Lorena, Musumeci Teresa, Ruozi Barbara, Pignatello Rosario
Department of Drug Sciences, Section of Pharmaceutical Technology, University of Catania, 95125 Catania, Italy.
Department of Civil Engineering and Architecture (DICAR), University of Catania, 95125 Catania, Italy.
Pharmaceuticals (Basel). 2020 Jun 24;13(6):131. doi: 10.3390/ph13060131.
Development of pH-dependent systems for colon delivery of natural active ingredients is an attractive area of research in the field of nutraceutical products. This study was focused on Eudraguard resins, that are methacrylate copolymers approved as "food grade" by European Commission and useful for the production of food supplements. In particular, Eudraguard Biotic (EUG-B), characterized by a pH-dependent solubility and Eudraguard Control (EUG-C), whose chemical properties support a prolonged release of the encapsulated compounds, were tested. To obtain EUG microparticles, different preparation techniques were tested, in order to optimize the preparation method and observe the effect upon drug encapsulation and specific colonic release. Unloaded microparticles were initially produced to evaluate the influence of polymer characteristics on the formulation process; subsequently microparticles loaded with quercetin (QUE) as a low solubility model drug were prepared. The characterization of microparticles in the solid-state (FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry) indicated that QUE was uniformly dispersed in a non-crystalline state in the polymeric network, without strong signs of chemical interactions. Finally, to assess the ability of EUG-C and EUG-B to control the drug release in the gastric environment, and to allow an increased release at a colonic level, suitable in vitro release tests were carried out by simulating the pH variations along the gastro-intestinal tract. Among the evaluated preparation methods, those in which an aqueous phase was not present, and in particular the emulsion-solvent evaporation method produced the best microparticle systems. The in vitro tests showed a limited drug release at a gastric level and a good specific colon release.
开发用于天然活性成分结肠递送的pH依赖性系统是营养保健品领域一个有吸引力的研究方向。本研究聚焦于Eudraguard树脂，它是一种甲基丙烯酸酯共聚物，被欧盟委员会批准为“食品级”，可用于生产食品补充剂。具体而言，测试了具有pH依赖性溶解性的Eudraguard Biotic（EUG-B）和其化学性质有助于延长包封化合物释放的Eudraguard Control（EUG-C）。为了获得EUG微粒，测试了不同的制备技术，以优化制备方法并观察其对药物包封和特定结肠释放的影响。首先制备未负载微粒以评估聚合物特性对制剂过程的影响；随后制备负载槲皮素（QUE）作为低溶解度模型药物的微粒。固态微粒的表征（傅里叶变换红外光谱、差示扫描量热法和X射线衍射法）表明，QUE以非晶态均匀分散在聚合物网络中，没有明显的化学相互作用迹象。最后，为了评估EUG-C和EUG-B在胃环境中控制药物释放以及在结肠水平实现增加释放的能力，通过模拟胃肠道沿线的pH变化进行了合适的体外释放试验。在评估的制备方法中，那些不存在水相的方法，特别是乳液-溶剂蒸发法产生了最佳的微粒系统。体外试验显示在胃水平药物释放有限，在结肠有良好的特定释放。
