Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Biotechnology Discovery Research, Indianapolis, IN, 46285, USA.
Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Synthetic Molecule Design and Development, Indianapolis, IN, 46285, USA.
Pharm Res. 2024 Nov;41(11):2259-2270. doi: 10.1007/s11095-024-03785-0. Epub 2024 Nov 1.
The oral absorption of a peptide is driven by a high local concentration of a permeation enhancer (PE) in the gastrointestinal tract. We hypothesized that a controlled release of both PE and peptide from a solid formulation, capable of maintaining an effective co-localized concentration of PE and peptide could enhance oral peptide absorption. In this study, we aimed to develop a 3D-printed two-compartment capsular device with controlled pulsatile release of peptide and sodium caprate (C10).
3D-printed two-compartment capsular device was fabricated using a fused deposition modeling method. This device was then filled with LY peptide and C10. The release profile was modulated by changing the thickness and polymer type of the capsular device. USP apparatus II dissolution test was used to evaluate the impacts of device thickness and polymer selection on release profile in vitro. An optimal device was then enteric coated with HPMCAS.
A strong linear relationship between the thickness of capsular devices and the delay in the release onset time was observed. An increase in the device thickness or the use of PLA decreased the release rate. The capsular device with compartment 1, compartment 2 and fence thickness of 0.4; 0.95 and 0.5 mm, respectively, and the use of PVA achieved desired pulsatile release profiles of both peptide and C10. Furthermore, enteric-coated capsular devices with HPMCAS had similar pulsatile release profiles compared to non-enteric coated devices.
These findings suggest potential application of 3D-printing techniques in the formulation development for complex modified drug release products.
肽的口服吸收是由胃肠道中高局部浓度的渗透增强剂（PE）驱动的。我们假设，从固体制剂中控制释放 PE 和肽，并能够维持有效的局部共存浓度的 PE 和肽，可增强口服肽的吸收。在这项研究中，我们旨在开发一种具有受控脉冲释放肽和月桂酸钠（C10）的 3D 打印两腔胶囊装置。
使用熔融沉积建模方法制造 3D 打印两腔胶囊装置。然后将该装置填充有 LY 肽和 C10。通过改变胶囊装置的厚度和聚合物类型来调节释放曲线。使用 USP 仪器 II 溶解试验评估装置厚度和聚合物选择对体外释放曲线的影响。然后用 HPMCAS 对最佳装置进行肠溶包衣。
观察到胶囊装置厚度与释放起始时间延迟之间存在很强的线性关系。装置厚度的增加或 PLA 的使用会降低释放速率。具有腔室 1、腔室 2 和围栏厚度分别为 0.4、0.95 和 0.5 毫米的胶囊装置，以及使用 PVA，实现了对肽和 C10 的理想脉冲释放曲线。此外，与非肠溶包衣装置相比，具有 HPMCAS 的肠溶包衣胶囊装置具有相似的脉冲释放曲线。
这些发现表明 3D 打印技术在复杂改良药物释放产品的制剂开发中具有潜在的应用。
