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

Abstract

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.

Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy

“…The spray-drying parameters were adjusted using standard procedures 22−26 in order to afford the final formulations and particle sizes given in Table 1. 27,28 DNP NMR Spectroscopy. DNP-enhanced solid-state NMR experiments were performed using a 9.4 T Bruker Avance III HD NMR spectrometer equipped with a 3.2 mm LTMAS DNP probe in triple resonance mode 1 H/ 13 C/ 15 N. The probe operated at sample temperatures of about 100 K using a Bruker LTMAS cabinet.…”

“…The latter was then used in a Büchi 290 spray-drier to produce a fine mist and dry it. The spray-drying parameters were adjusted using standard procedures − in order to afford the final formulations and particle sizes given in Table . , …”

“…The spray-drying parameters were adjusted using standard procedures 22 − 26 in order to afford the final formulations and particle sizes given in Table 1 . 27 , 28 …”