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Study breakdown

Spray Drying Process Achieves Over 83% Yield for Glucagon Peptide Without Degradation

evidence
The takeaway

A data-driven spray drying process for glucagon achieved yields above 83% with trehalose stabilization, producing stable peptide powder without significant aggregation or degradation.

>83% yield

Spray drying glucagon and glucagon-trehalose formulations achieved yields above 83.24% while maintaining peptide integrity — no significant aggregation or degradation

What the researchers found

The spray drying process achieved yields up to 84.67% for trehalose and >83.24% for glucagon and glucagon-trehalose formulations. A psychrometric process model identified optimal operating conditions that significantly reduced residual moisture and particle agglomeration compared to non-optimal drying. Critically, extensive peptide aggregation or fibrillation (a common problem with glucagon) was not observed in the spray-dried product, confirming the process preserved peptide integrity.

Why it matters

Peptide drugs like glucagon are notoriously difficult to manufacture because they're fragile and prone to degradation, aggregation, and fibrillation. Most peptide drugs are freeze-dried, which is slow and expensive. If spray drying can reliably produce stable peptide powders at higher throughput, it could reduce manufacturing costs and improve the supply of life-saving peptide medications.

How the study worked

Single droplet drying experiments characterized particle formation. Lab-scale spray drying was implemented with in-line process analytical technology (PAT) monitoring temperature, humidity, pressure, and feed rate in a data acquisition framework. Off-line characterization assessed residual moisture, solid state structure, particle size/morphology, and peptide fibrillation/degradation. A psychrometric model guided identification of feasible operating conditions.

What this study cannot tell us

The study was conducted at lab-scale only; scale-up to commercial manufacturing may introduce additional challenges. Only glucagon was tested, and other peptides with different stability profiles may behave differently. Long-term storage stability of the spray-dried glucagon was not assessed. The study did not compare the bioactivity of spray-dried glucagon to freeze-dried glucagon in biological assays.

How to read the evidence

This is a pharmaceutical process development study with rigorous analytical characterization. The data-driven approach and comprehensive product characterization provide strong evidence for the feasibility of spray drying glucagon, but scale-up validation and long-term stability studies are still needed.

When this study was published

Published in 2020, this study contributes to ongoing efforts to improve peptide drug manufacturing. Spray drying technology for biologics continues to advance.

The bigger picture

As the peptide therapeutics market grows rapidly (with drugs like semaglutide, tirzepatide, and others), efficient manufacturing becomes critical. This study demonstrates that spray drying — a faster, more scalable alternative to freeze-drying — can handle sensitive peptides like glucagon without compromising quality. The data-driven approach could accelerate formulation development for the growing pipeline of peptide drugs.

Questions still open

  • Can this spray drying approach be successfully scaled up for commercial peptide drug manufacturing?
  • How does the long-term storage stability of spray-dried glucagon compare to conventionally freeze-dried glucagon?
  • Could this process be adapted for larger, more complex peptide therapeutics like GLP-1 receptor agonists?

Common questions

What is spray drying and why is it useful for peptide drugs?
Spray drying rapidly converts a liquid solution into a dry powder by spraying it into hot air. It's faster and more scalable than freeze-drying (the traditional method for peptide drugs), but peptides are fragile and can be damaged by heat. This study showed that with careful process control, spray drying can produce stable glucagon powder without degrading the peptide.
Why is glucagon manufacturing important?
Glucagon is a life-saving peptide hormone used to treat severe low blood sugar (hypoglycemia), which can be fatal if untreated. Improving its manufacturing process could reduce costs and improve availability. The techniques developed here could also apply to other peptide drugs in the growing peptide therapeutics market.

Read the original research

Peptide Isolation via Spray Drying: Particle Formation, Process Design and Implementation for the Production of Spray Dried Glucagon.

Pharmaceutical research, 37(12), 255

Citation

Doerr, Frederik J S; Burns, Lee J; Lee, Becky; Hinds, Jeremy; Davis-Harrison, Rebecca L; Frank, Scott A; Florence, Alastair J. (2020). Peptide Isolation via Spray Drying: Particle Formation, Process Design and Implementation for the Production of Spray Dried Glucagon.. Pharmaceutical research, 37(12), 255. https://doi.org/10.1007/s11095-020-02942-5