Geng Yuhao, Williams Gareth R
UCL School of Pharmacy, 29 - 39 Brunswick Square, London, WC1N 1AX.
UCL School of Pharmacy, 29 - 39 Brunswick Square, London, WC1N 1AX.
Int J Pharm. 2023 Oct 27:123557. doi: 10.1016/j.ijpharm.2023.123557.
In this work ethyl cellulose (EC) was used as the matrix polymer and loaded with captopril, with the goal to fabricate electrospun fibers as potential sustained-release floating gastro-retentive drug delivery systems. Fibers were prepared with monoaxial and coaxial electrospinning, and both bench-top and scaled-up (needle-based) methods were explored. With monoaxial electrospinning, EC-based fibers in the shape of cylinders and with smooth surfaces were obtained both at 1 and 20 mL/h. For coaxial electrospinning, the drug was encapsulated in the core end fibers generated with core/shell feeding rates of 0.5/1 and 5/10 mL/h. The fibers were cylindrical in shape with a wrinkled surface, and confocal microscopy suggested them to have a core/shell structure. X-ray diffraction and differential scanning calorimetry results showed that all the fibers were amorphous. The encapsulation efficiency of all the formulations was almost 100%. Release studies in simulated gastric fluid indicated that the monoaxial electrospun fibers gave slower release profiles compared with a physical mixture of captopril and EC, but there was still an initial "burst" of release at the start of the experiment. Fibers with low drug-loading (9.09% w/w) showed a slower release than fibers with high loading (23.08% w/w). The coaxial fibers exhibited sustained release profiles with reduced initial burst release. Both monoaxial and coaxial fibers could float on the surface of simulated gastric fluid for over 24 hours at 37 °C. After storage under ambient conditions (19-21°C, relative humidity 30-40%) for 8 weeks, all the fibers remained amorphous and the release profiles had no significant changes compared with fresh fibers. This work thus highlights the potential of coaxial electrospinning for fabricating a sustained-release floating gastro-retentive drug delivery system for captopril.
在本研究中，乙基纤维素（EC）被用作基质聚合物并负载卡托普利，目的是制备电纺纤维作为潜在的缓释胃滞留药物递送系统。采用单轴和同轴电纺制备纤维，并探索了台式和放大（基于针头）方法。通过单轴电纺，在1和20 mL/h的流速下均获得了表面光滑的圆柱形EC基纤维。对于同轴电纺，药物被包裹在以0.5/1和5/10 mL/h的核/壳进料速率生成的核-壳型纤维中。这些纤维呈圆柱形，表面有褶皱，共聚焦显微镜显示它们具有核-壳结构。X射线衍射和差示扫描量热法结果表明，所有纤维均为无定形。所有制剂的包封率几乎为100%。在模拟胃液中的释放研究表明，与卡托普利和EC的物理混合物相比，单轴电纺纤维的释放曲线较慢，但在实验开始时仍有初始“突释”。低载药量（9.09% w/w）的纤维比高载药量（23.08% w/w）的纤维释放更慢。同轴纤维呈现出缓释曲线，初始突释减少。单轴和同轴纤维在37°C下均可在模拟胃液表面漂浮超过24小时。在环境条件（19-21°C，相对湿度30-40%）下储存8周后，所有纤维仍保持无定形，与新鲜纤维相比，释放曲线无显著变化。因此，这项工作突出了同轴电纺在制备用于卡托普利的缓释胃滞留药物递送系统方面的潜力。
