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

PURPOSE: Spray 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. METHODS: Single 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. RESULTS: A 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11095-020-02942-5.