Wood-Yang Amy J, Palacios Joshua I, Sankaranarayanan Abishek, Prausnitz Mark R
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Wallace Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Pharmaceutics. 2025 Sep 3;17(9):1156. doi: 10.3390/pharmaceutics17091156.
Oral delivery of biologics offers advantages for patient access and adherence compared to injection, but suffers from low bioavailability due to mucosal barriers and drug degradation in the gastrointestinal tract. We previously developed an oral self-pressurized aerosol (OSPRAE) capsule that uses effervescent excipients to generate CO gas, building internal pressure to eject powdered drug at high velocity across intestinal mucosa. Here, we developed two key design improvements: (i) an enteric covering to protect the capsule delivery orifice in gastric fluids and (ii) reduced humidity content of capsules to extend shelf-life. Enteric-covered capsules prevented drug release in simulated gastric fluid and then enabled rapid release upon transfer to simulated intestinal fluid. Burst pressure for enteric-covered capsules was ~3-4 times higher than non-covered capsules. After storage for up to three days, the capsules' effervescent excipients pre-reacted, making them unable to achieve high pressure during subsequent use. To address this limitation, we prepared capsules under reduced humidity conditions, which inhibited pre-reaction of effervescent excipients during storage, and a polyurethane coating to improve water uptake into the capsule to drive the effervescence reaction in intestinal fluid. These design improvements enable improved functionality of OSPRAE capsules for continued translation in pre-clinical and future clinical development.
与注射给药相比，生物制剂口服给药在患者接受度和依从性方面具有优势，但由于黏膜屏障和胃肠道中的药物降解，其生物利用度较低。我们之前开发了一种口服自加压气雾剂（OSPRAE）胶囊，该胶囊使用泡腾赋形剂产生CO气体，建立内部压力以高速将粉末状药物喷射穿过肠黏膜。在此，我们进行了两项关键的设计改进：（i）一种肠溶包衣，以保护胶囊在胃液中的输送孔；（ii）降低胶囊的湿度含量以延长保质期。肠溶包衣胶囊可防止药物在模拟胃液中释放，然后在转移至模拟肠液时实现快速释放。肠溶包衣胶囊的爆破压力比未包衣胶囊高约3至4倍。储存长达三天后，胶囊的泡腾赋形剂会提前发生反应，使其在后续使用过程中无法达到高压。为了解决这一限制，我们在降低湿度的条件下制备胶囊，这可抑制储存期间泡腾赋形剂的提前反应，并使用聚氨酯涂层来改善胶囊对水分的吸收，以驱动肠液中的泡腾反应。这些设计改进提高了OSPRAE胶囊的功能，以便在临床前和未来的临床开发中继续进行转化。
