Muselík Jan, Komersová Alena, Elbl Jan, Svoboda Roman, Matzick Kevin, Macháčková Jana, Nevyhoštěná Marie, Krepelková Zuzana, Novotný Jaroslav, Franc Aleš
Department of Pharmaceutical Technology, Faculty of Pharmacy, Masaryk University, Palackého tř. 1, 612 00 Brno, Czech Republic.
Department of Physical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 95, 532 10 Pardubice, Czech Republic.
J Pharm Sci. 2025 May 8;114(7):103815. doi: 10.1016/j.xphs.2025.103815.
The present study aims to develop capsules employing hot melt extrusion (HME) and fused deposition modeling (FDM) three-dimensional (3D) printing approach. The primary objective was to establish a colon drug delivery system (CDDS) based on multiple release mechanisms. In the study, 3D printed hydroxypropylmethylcellulose (HPMC) based capsules containing polysaccharides (alginate, chitosan pectin from citrus and pectin from apple) were used to provide a time-triggered and microbiota-triggered release mechanism. Thirteen capsule compositions were tested, and physico-chemical properties, disintegration time, dissolution characteristic (lag time) and 50 days accelerated stability were assessed. In addition, an enteric coating by Eudragit S was tested to enhance protection against the gastric environment. Disintegration time of the capsule under in vivo conditions was verified in healthy volunteers by oral administration of the caffeine-loaded capsule and determination of the first-appearance time of caffeine in the saliva. Furthermore, in vivo monitoring of the transition time in piglets was performed by X-ray examination after oral administration of BaSO-loaded capsules. Optimal capsule composition was identified as HPMC and pectin from citrus in 80:20 wt% ratio. Printed capsules showed suitable physico-chemical properties, lag time and stability. Minimal drug release in the upper gastrointestinal tract (∼5 %) for the first 8-10 h was ensured by both coated and uncoated capsules. In addition, as demonstrated by the in vivo transition time monitoring assay, with accelerated passage of the capsule through the gastrointestinal tract, degradation is significantly accelerated (∼4 h) by a microbiota-triggered mechanism, effectively targeting the colon. Using 3D printing, a colonic-specific drug delivery system was prepared that could potentially be suitable for treating patients with various intestinal physiological conditions.
本研究旨在采用热熔挤出（HME）和熔融沉积建模（FDM）三维（3D）打印方法开发胶囊。主要目标是建立一种基于多种释放机制的结肠给药系统（CDDS）。在该研究中，使用3D打印的基于羟丙基甲基纤维素（HPMC）的胶囊，其含有多糖（藻酸盐、柑橘壳聚糖果胶和苹果果胶），以提供时间触发和微生物群触发的释放机制。测试了13种胶囊组合物，并评估了其物理化学性质、崩解时间、溶解特性（滞后时间）和50天加速稳定性。此外，还测试了用Eudragit S进行肠溶包衣，以增强对胃环境的保护。通过口服含咖啡因的胶囊并测定唾液中咖啡因的首次出现时间，在健康志愿者中验证了体内条件下胶囊的崩解时间。此外，口服含硫酸钡的胶囊后，通过X射线检查对仔猪的过渡时间进行了体内监测。确定最佳胶囊组合物为重量比为80:20的HPMC和柑橘果胶。打印的胶囊显示出合适的物理化学性质、滞后时间和稳定性。包衣和未包衣的胶囊在前8-10小时内均确保在上消化道中的药物释放最少（约5%）。此外，如体内过渡时间监测试验所示，随着胶囊在胃肠道中的快速通过，微生物群触发机制可显著加速降解（约4小时），有效地靶向结肠。使用3D打印制备了一种结肠特异性给药系统，该系统可能适用于治疗各种肠道生理状况的患者。
