Comparison of bulk and microfluidic methods to monitor the phase behaviour of nanoparticles during digestion of lipid-based drug formulations using in situ X-ray scattering.
File(s)2019Hong_PhaseChangeNPsDigestionXRay_Accepted.pdf (2.09 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-11-27
Date Acceptance
2019-11-02
Citation
Soft Matter, 2019, 15 (46), pp.9565-9578
ISSN
1744-683X
Publisher
Royal Society of Chemistry
Start Page
9565
End Page
9578
Journal / Book Title
Soft Matter
Volume
15
Issue
46
Copyright Statement
© The Royal Society of Chemistry 2019
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31724682
Subjects
03 Chemical Sciences
09 Engineering
02 Physical Sciences
Chemical Physics
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2019-11-14