The influence of lysozyme on mannitol polymorphism in freeze-dried and spray-dried formulations depends on the selection of the drying process

TY - JOUR

T1 - The influence of lysozyme on mannitol polymorphism in freeze-dried and spray-dried formulations depends on the selection of the drying process

AU - Grohganz, Holger

AU - Lee, Yan-Ying

AU - Rantanen, Jukka

AU - Yang, Mingshi

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/4/15

Y1 - 2013/4/15

N2 - Freeze-drying and spray-drying are often applied drying techniques for biopharmaceutical formulations. The formation of different solid forms upon drying is often dependent on the complex interplay between excipient selection and process parameters. The purpose of this study was to investigate the influence of the chosen drying method on the solid state form. Mannitol-lysozyme solutions of 20 mg/mL, with the amount of lysozyme varying between 2.5% and 50% (w/w) of total solid content, were freeze-dried and spray-dried, respectively. The resulting solid state of mannitol was analysed by near-infrared spectroscopy in combination with multivariate analysis and further, results were verified with X-ray powder diffraction. It was seen that the prevalence of the mannitol polymorphic form shifted from β-mannitol to δ-mannitol with increasing protein concentration in freeze-dried formulations. In spray-dried formulations an increase in protein concentration resulted in a shift from β-mannitol to α-mannitol. An increase in final drying temperature of the freeze-drying process towards the temperature of the spray-drying process did not lead to significant changes. It can thus be concluded that it is the drying process in itself, rather than the temperature, that leads to the observed solid state changes.

AB - Freeze-drying and spray-drying are often applied drying techniques for biopharmaceutical formulations. The formation of different solid forms upon drying is often dependent on the complex interplay between excipient selection and process parameters. The purpose of this study was to investigate the influence of the chosen drying method on the solid state form. Mannitol-lysozyme solutions of 20 mg/mL, with the amount of lysozyme varying between 2.5% and 50% (w/w) of total solid content, were freeze-dried and spray-dried, respectively. The resulting solid state of mannitol was analysed by near-infrared spectroscopy in combination with multivariate analysis and further, results were verified with X-ray powder diffraction. It was seen that the prevalence of the mannitol polymorphic form shifted from β-mannitol to δ-mannitol with increasing protein concentration in freeze-dried formulations. In spray-dried formulations an increase in protein concentration resulted in a shift from β-mannitol to α-mannitol. An increase in final drying temperature of the freeze-drying process towards the temperature of the spray-drying process did not lead to significant changes. It can thus be concluded that it is the drying process in itself, rather than the temperature, that leads to the observed solid state changes.

U2 - 10.1016/j.ijpharm.2013.03.003

DO - 10.1016/j.ijpharm.2013.03.003

M3 - Journal article

C2 - 23500620

SN - 0378-5173

VL - 447

SP - 224

EP - 230

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -