Spray Dryer Gas Heater Material for Low-Impurity Semaglutide

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Solution Overview

Problem

The generation of impurities during the spray drying process of semaglutide is attributed to the interaction between acetaldehyde and the peptide, which is influenced by the material of the gas heater, leading to increased impurity levels when using Incoloy 800 compared to stainless steel 316.

Innovation Solution

The use of a gas heater with an inner surface comprising iron and less than 18.5% chromium, such as stainless steel 316, reduces the generation of impurities by minimizing the formation of acetaldehyde during the spray drying process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If GLP-1 peptide is spray dried using conventional methods, then the peptide can be converted to powder form, but the peptide aggregates and loses potency

Engineering Contradiction:
Improvepeptide potencyVSAvoidpeptide aggregation
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

A stabilizing agent is introduced as an intermediary substance during the spray drying process. This stabilizing agent prevents peptide aggregation by maintaining proper spacing and conformation of peptide molecules during the transition from liquid to powder form, thereby preserving peptide potency while enabling powder formation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention modifies critical process parameters including spray drying temperature, inlet/outlet temperature differential, and peptide concentration in the solution. These parameter changes create optimal conditions that prevent peptide aggregation during drying while maintaining potency, resolving the contradiction between powder formation and peptide stability.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If peptide concentration is increased to improve efficiency, then less processing time is required, but peptide aggregates form more readily

Engineering Contradiction:
Improveprocessing efficiencyVSAvoidpeptide aggregation
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The stabilizing agent acts as a mediator that enables higher peptide concentrations to be processed without aggregation. By introducing this intermediary substance, the system can achieve improved productivity through higher concentrations while the stabilizing agent prevents the harmful aggregation effects that would normally occur at such concentrations.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If spray drying temperature is increased to reduce drying time, then productivity improves, but peptide potency is reduced due to thermal degradation

Engineering Contradiction:
Improvedrying speedVSAvoidpeptide potency
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The invention optimizes the temperature parameters of the spray drying process, specifically controlling the inlet and outlet temperatures within a range that enables sufficiently fast drying for productivity while preventing thermal degradation that would reduce peptide potency. This parameter optimization resolves the contradiction between drying speed and peptide stability.

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The implementation of a gas heater with a specific chromium content significantly decreases impurity levels, enhancing the purity and stability of the semaglutide product.

Implementation Method 1

spray drying a glp-1 peptide

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP3938094B1Process for spray drying a GLP-1 peptide
Publication Date: 2026.05.06 NOVO NORDISK AS
  • EP3938094B1 patent drawingFigure 1~2

AI summary

The present invention relates to a process for spray drying of a feed solution comprising semaglutide, said process comprising introducing the feed solution comprising semaglutide in a solvent into a spray dryer and introducing an atomising gas and a drying gas, characterised in that the spray dryer comprises a gas heater for the drying gas with an inner surface comprising iron and less than 18.5% chromium.