New Lyophilization Methods Stabilize Insulin for Oral Solid Dosage Forms | Research

The takeaway

Co-lyophilized ternary insulin-sucrose-polymer systems achieved enhanced stability against manufacturing and storage stresses while maintaining amorphous structure for oral dosage incorporation.

Oral insulin enabled
Ternary lyophilization protects insulin through manufacturing, storage, and GI conditions — a key barrier for oral peptide drugs

What the researchers found

Ternary insulin-sucrose-polymer lyophilized systems maintained amorphous glass stability and protected insulin bioactivity through manufacturing compression, temperature stress, storage humidity, and simulated GI conditions.

Why it matters

Oral insulin has been pursued for decades without success. Solving the stability problem during manufacturing and storage is a crucial step toward making it reality.

How the study worked

Co-lyophilization of insulin with sucrose and various polymers, characterization by DSC, FTIR, and stability testing under manufacturing (compression), storage (ICH conditions), and simulated GI challenges.

What this study cannot tell us

In vitro stability testing. Oral bioavailability in vivo not assessed. Specific polymer combinations need optimization for each peptide drug. Manufacturing scale-up needed.

How to read the evidence

Thorough formulation science study with comprehensive stability characterization. In vitro only; bioavailability unknown.

When this study was published

Published in 2025.

The bigger picture

This formulation approach could be applied to any peptide drug that needs oral delivery, addressing a fundamental barrier in peptide pharmaceutical development.

Questions still open

Which polymer-sucrose combination provides the best long-term insulin stability?
Would this formulation achieve meaningful oral insulin bioavailability in humans?
Can the approach be extended to GLP-1 peptides for oral delivery?

Common questions

Why can't you just put insulin in a pill?

Insulin is a fragile peptide that breaks down during pill manufacturing (compression), storage, and in stomach acid. This study solved the manufacturing and storage problems by freeze-drying insulin with stabilizing sugars and polymers.

Is oral insulin coming soon?

This is one piece of the puzzle. The stability problem during manufacturing and storage is addressed here, but achieving sufficient absorption from the gut remains the main remaining challenge.

Read the original research

Design of co-lyophilised ternary insulin-sucrose-polymer systems with enhanced amorphous glass stability.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 218, 107450

View on PubMed ↗Publisher’s paper ↗

Citation

Giannachi, Claudia; Allen, Evin; Vucen, Sonja; Crean, Abina. (2026). Design of co-lyophilised ternary insulin-sucrose-polymer systems with enhanced amorphous glass stability.. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 218, 107450. https://doi.org/10.1016/j.ejps.2026.107450