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

Frederik J S Doerr,Alastair J Florence,Scott A Frank,Becky Lee,Rebecca L Davis-Harrison,Lee J Burns,Jeremy Hinds

doi:10.1007/s11095-020-02942-5

Abstract

PurposeSpray drying plays an important role in the pharmaceutical industry for product development of sensitive bio-pharmaceutical formulations. Process design, implementation and optimisation require in-depth knowledge of process-product interactions. Here, an integrated approach for the rapid, early-stage spray drying process development of trehalose and glucagon on lab-scale is presented.MethodsSingle droplet drying experiments were used to investigate the particle formation process. Process implementation was supported using in-line process analytical technology within a data acquisition framework recording temperature, humidity, pressure and feed rate. During process implementation, off-line product characterisation provided additional information on key product properties related to residual moisture, solid state structure, particle size/morphology and peptide fibrillation/degradation.ResultsA psychrometric process model allowed the identification of feasible operating conditions for spray drying trehalose, achieving high yields of up to 84.67%, and significantly reduced levels of residual moisture and particle agglomeration compared to product obtained during non-optimal drying. The process was further translated to produce powders of glucagon and glucagon-trehalose formulations with yields of >83.24%. Extensive peptide aggregation or degradation was not observed.ConclusionsThe presented data-driven process development concept can be applied to address future isolation problems on lab-scale and facilitate a systematic implementation of spray drying for the manufacturing of sensitive bio-pharmaceutical formulations.

Highlights

Techniques for the isolation of peptide-based systems are of considerable interest for the development of novel pharmaceutical peptide products [1, 2]
The presented data-driven process development concept can be applied to address future isolation problems on lab-scale and facilitate a systematic implementation of spray drying for the manufacturing of sensitive bio-pharmaceutical formulations
The results demonstrate that vacuum drying could be utilised on lab-scale as a secondary drying step for spray dried powders produced during early process development, but is most effective for pure GLUC peptide solids

Summary

Introduction

Techniques for the isolation of peptide-based systems are of considerable interest for the development of novel pharmaceutical peptide products [1, 2]. Freeze drying and spray drying are often methods of choice for the solidification of unstable or sensitive bio-pharmaceutical formulations. Operating conditions must be carefully selected during process development to avoid thermal damage due to exposure of the material to excessive drying temperatures or mechanical damage caused by shear stress during the pumping of liquid feed and atomisation in the spray nozzle. Despite these process risks, the rapid drying kinetics and the evaporative cooling effect allow the processing of heat sensitive materials. Carbohydrates are often employed as excipients as they can preserve the protein’s active conformation via preferential exclusion, water replacement and glass immobilization mechanisms [9,10,11]

Methods

Results

Conclusion