Liraglutide aggregation in prefilled syringes is driven by dual interfacial stress from air-water and silicone oil-water interfaces acting together, not by either stress alone.
Dual interfaces, not oneNeither air nor silicone oil alone causes liraglutide aggregation — their combined interfacial stress is the culprit
What the researchers found
Dual air-water + silicone oil-water interfacial stress, not either alone, drives liraglutide fibrillation in PFS. First-ever SRS visualization of peptide adsorption on silicone oil at sub-micrometer resolution. NMR showed aggregation without specific binding.
Why it matters
GLP-1 drugs in prefilled syringes must remain stable. Understanding the dual-interface mechanism enables design of better devices that prevent drug degradation.
How the study worked
Biophysical characterization (SEC, CD, ThT fluorescence) of liraglutide stability under varying silicone oil, headspace, and agitation, with SRS chemical imaging and NMR spectroscopy for molecular interaction analysis.
What this study cannot tell us
In vitro accelerated stress conditions may not perfectly replicate clinical storage. Specific to liraglutide; other peptides may behave differently.
How to read the evidence
Rigorous biophysical characterization with novel imaging techniques. Definitive mechanistic insight for PFS design.
When this study was published
Published in 2025.
The bigger picture
Peptide drug stability in delivery devices is a critical but underappreciated pharmaceutical challenge. This molecular-level understanding enables better device design for all peptide drugs.
Questions still open
- Can headspace-free syringe designs eliminate the fibrillation risk?
- Would alternative lubricants to silicone oil solve the problem?
- Does this apply to semaglutide and tirzepatide in their PFS formulations?
Common questions
Why does liraglutide sometimes form clumps in syringes?
Does this affect my medication?
Read the original research
Molecular Mechanisms of Liraglutide Aggregation Induced by Dual Air-Water and Silicone-Oil-Water Interfacial Stress.
Molecular pharmaceutics, 23(2), 1295-1309
Citation
Hamada, Naomi; Cutts, Aaron; Song, Jing; Hu, Guangli; Fu, Dan; Wuelfing, W Peter; Su, Yongchao; Ling, Jing. (2026). Molecular Mechanisms of Liraglutide Aggregation Induced by Dual Air-Water and Silicone-Oil-Water Interfacial Stress.. Molecular pharmaceutics, 23(2), 1295-1309. https://doi.org/10.1021/acs.molpharmaceut.5c01837