Lorenzo-Lamosa M L, Remuñán-López C, Vila-Jato J L, Alonso M J
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Spain.
J Control Release. 1998 Mar 2;52(1-2):109-18. doi: 10.1016/s0168-3659(97)00203-4.
Among the different approaches to achieve colon-selective drug delivery, the use of polymers, specifically biodegraded by colonic bacteria, holds great promise. In this work a new system which combines specific biodegradability and pH-dependent release is presented. The system consists of chitosan (CS) microcores entrapped within acrylic microspheres. Sodium diclofenac (SD), used as a model drug, was efficiently entrapped within CS microcores using spray-drying and then microencapsulated into Eudragit L-100 and Eudragit S-100 using an oil-in-oil solvent evaporation method. The size of the CS microcores was small (1.8-2.9 microns) and they were encapsulated within Eudragit microspheres (size between 152 and 233 microns) forming a multireservoir system. Even though CS dissolves very fast in acidic media, at pH 7.4, SD release from CS microcores was delayed, the release rate being adjustable (50% dissolved within 30-120 min) by changing the CS molecular weight (MW) or the type of CS salt. Furthermore, by coating the CS microcores with Eudragit, perfect pH-dependent release profiles were attained. No release was observed at acidic pHs, however, when reaching the Eudragit pH solubility, a continuous release for a variable time (8-12 h) was achieved. A combined mechanism of release is proposed, which considers the dissolution of the Eudragit coating, the swelling of the CS microcores and the dissolution of SD and its further diffusion through the CS gel cores. In addition, infrared (IR) spectra revealed that there was an ionic interaction between the amine groups of CS and the carboxyl groups of Eudragit, which provided the system with a new element for controlling the release. In conclusion, this work presents new approaches for the modification of CS as well as a new system with a great potential for colonic drug delivery.
在实现结肠选择性药物递送的不同方法中，使用聚合物，特别是可被结肠细菌生物降解的聚合物，具有很大的前景。在这项工作中，提出了一种结合特定生物降解性和pH依赖性释放的新系统。该系统由包裹在丙烯酸微球内的壳聚糖（CS）微核组成。将双氯芬酸钠（SD）用作模型药物，通过喷雾干燥将其有效地包裹在CS微核内，然后使用油包油溶剂蒸发法将其微囊化到Eudragit L - 100和Eudragit S - 100中。CS微核的尺寸很小（1.8 - 2.9微米），它们被包裹在Eudragit微球（尺寸在152至233微米之间）内，形成了一个多储库系统。尽管CS在酸性介质中溶解非常快，但在pH 7.4时，SD从CS微核中的释放被延迟，通过改变CS的分子量（MW）或CS盐的类型，释放速率是可调的（50%在30 - 120分钟内溶解）。此外，通过用Eudragit包衣CS微核，获得了完美的pH依赖性释放曲线。在酸性pH值下未观察到释放，然而，当达到Eudragit的pH溶解度时，实现了可变时间（8 - 12小时）的持续释放。提出了一种联合释放机制，该机制考虑了Eudragit包衣的溶解、CS微核的溶胀以及SD的溶解及其通过CS凝胶核的进一步扩散。此外，红外（IR）光谱显示CS的胺基与Eudragit的羧基之间存在离子相互作用，这为该系统提供了一个控制释放的新因素。总之，这项工作提出了修饰CS的新方法以及一种具有结肠药物递送巨大潜力的新系统。
