Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia.
Soft Matter. 2019 Nov 27;15(46):9565-9578. doi: 10.1039/c9sm01440c.
The performance of orally administered lipid-based drug formulations is crucially dependent on digestion, and understanding the colloidal structures formed during digestion is necessary for rational formulation design. Previous studies using the established bulk pH-stat approach (Hong et al. 2015), coupled to synchrotron small angle X-ray scattering (SAXS), have begun to shed light on this subject. Such studies of digestion using in situ SAXS measurements are complex and have limitations regarding the resolution of intermediate structures. Using a microfluidic device, the digestion of lipid systems may be monitored with far better control over the mixing of the components and the application of enzyme, thereby elucidating a finer understanding of the structural progression of these lipid systems. This work compares a simple T-junction microcapillary device and a custom-built microfluidic chip featuring hydrodynamic flow focusing, with an equivalent experiment with the full scale pH-stat approach. Both microfluidic devices were found to be suitable for in situ SAXS measurements in tracking the kinetics with improved time and signal sensitivity compared to other microfluidic devices studying similar lipid-based systems, and producing more consistent and controllable structural transformations. Particle sizing of the nanoparticles produced in the microfluidic devices were more consistent than the pH-stat approach.
口服脂质药物制剂的性能在很大程度上取决于消化，而了解消化过程中形成的胶体结构对于合理的制剂设计是必要的。先前使用既定的批量 pH -stat 方法（Hong 等人，2015 年）结合同步加速器小角 X 射线散射（SAXS）的研究已经开始阐明这一主题。使用原位 SAXS 测量进行的此类消化研究很复杂，并且在中间结构的分辨率方面存在限制。使用微流控装置，可以更好地控制组件的混合和酶的应用来监测脂质系统的消化，从而更深入地了解这些脂质系统的结构进展。这项工作比较了简单的 T 形分叉微毛细管装置和具有流体动力学流动聚焦功能的定制微流控芯片，与具有全规模 pH-stat 方法的等效实验进行了比较。发现这两种微流控装置都适合在原位 SAXS 测量中跟踪动力学，与研究类似脂质基系统的其他微流控装置相比，具有更好的时间和信号灵敏度，并且产生更一致和可控的结构转变。与 pH-stat 方法相比，在微流控装置中产生的纳米颗粒的粒径更一致。
