TY - JOUR
T1 - Impact of Different Saccharides on the In-Process Stability of a Protein Drug During Evaporative Drying
T2 - From Sessile Droplet Drying to Lab-Scale Spray Drying
AU - Dieplinger, Johanna
AU - Pinto, Joana T.
AU - Dekner, Michael
AU - Brachtl, Gerald
AU - Paudel, Amrit
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4/3
Y1 - 2023/4/3
N2 - Objectives: Solid biopharmaceutical products can circumvent lower temperature storage and transport and increase remote access with lower carbon emissions and energy consumption. Saccharides are known stabilizers in a solid protein produced via lyophilization and spray drying (SD). Thus, it is essential to understand the interactions between saccharides and proteins and the stabilization mechanism. Methods: A miniaturized single droplet drying (MD) method was developed to understand how different saccharides stabilize proteins during drying. We applied our MD to different aqueous saccharide-protein systems and transferred our findings to SD. Results: The poly- and oligosaccharides tend to destabilize the protein during drying. The oligosaccharide, Hydroxypropyl β-cyclodextrin (HPβCD) shows high aggregation at a high saccharide-to-protein molar ratio (S/P ratio) during MD, and the finding is supported by nanoDSF results. The polysaccharide, Dextran (DEX) leads to larger particles, whereas HPBCD leads to smaller particles. Furthermore, DEX is not able to stabilize the protein at higher S/P ratios either. In contrast, the disaccharide Trehalose Dihydrate (TD) does not increase or induce protein aggregation during the drying of the formulation. It can preserve the protein’s secondary structure during drying, already at low concentrations. Conclusion: During the drying of S/P formulations containing the saccharides TD and DEX, the MD approach could anticipate the in-process (in) stability of protein X at laboratory-scale SD. In contrast, for the systems with HPβCD, the results obtained by SD were contradictory to MD. This underlines that depending on the drying operation, careful consideration needs to be applied to the selection of saccharides and their ratios.
AB - Objectives: Solid biopharmaceutical products can circumvent lower temperature storage and transport and increase remote access with lower carbon emissions and energy consumption. Saccharides are known stabilizers in a solid protein produced via lyophilization and spray drying (SD). Thus, it is essential to understand the interactions between saccharides and proteins and the stabilization mechanism. Methods: A miniaturized single droplet drying (MD) method was developed to understand how different saccharides stabilize proteins during drying. We applied our MD to different aqueous saccharide-protein systems and transferred our findings to SD. Results: The poly- and oligosaccharides tend to destabilize the protein during drying. The oligosaccharide, Hydroxypropyl β-cyclodextrin (HPβCD) shows high aggregation at a high saccharide-to-protein molar ratio (S/P ratio) during MD, and the finding is supported by nanoDSF results. The polysaccharide, Dextran (DEX) leads to larger particles, whereas HPBCD leads to smaller particles. Furthermore, DEX is not able to stabilize the protein at higher S/P ratios either. In contrast, the disaccharide Trehalose Dihydrate (TD) does not increase or induce protein aggregation during the drying of the formulation. It can preserve the protein’s secondary structure during drying, already at low concentrations. Conclusion: During the drying of S/P formulations containing the saccharides TD and DEX, the MD approach could anticipate the in-process (in) stability of protein X at laboratory-scale SD. In contrast, for the systems with HPβCD, the results obtained by SD were contradictory to MD. This underlines that depending on the drying operation, careful consideration needs to be applied to the selection of saccharides and their ratios.
KW - biopharmaceutical
KW - miniaturized droplet drying
KW - saccharide
KW - spray drying
KW - stabilization
UR - http://www.scopus.com/inward/record.url?scp=85151408921&partnerID=8YFLogxK
U2 - 10.1007/s11095-023-03498-w
DO - 10.1007/s11095-023-03498-w
M3 - Article
C2 - 37012535
AN - SCOPUS:85151408921
SN - 0724-8741
VL - 40
SP - 1283
EP - 1298
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 5
ER -