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Insights into the influence of the cooling profile on the reconstitution times of amorphous lyophilized protein formulations

Beech, Karen E.; Biddlecombe, James G.; van der Walle, Christopher F.; Stevens, Lee A.; Rigby, Sean P.; Burley, Jonathan C.; Allen, Stephanie; Burley, Jonathan C.; Allena, Stephanie


Karen E. Beech

James G. Biddlecombe

Christopher F. van der Walle

Senior Research Fellow

Professor of Chemical Engineering

Professor of Pharmaceutical Biophysics

Stephanie Allena


Lyophilized protein formulations must be reconstituted back into solution prior to patient administration and in this regard long reconstitution times are not ideal. The factors that govern reconstitution time remain poorly understood. The aim of this research was to understand the influence of the lyophilization cooling profile (including annealing) on the resulting cake structure and reconstitution time. Three protein formulations (BSA 50 mg/ml, BSA 200 mg/ml and IgG1 40 mg/ml, all in 7% w/v sucrose) were investigated after cooling at either 0.5 °C/min, or quench cooling with liquid nitrogen with/without annealing. Significantly longer reconstitution times were observed for the lower protein concentration formulations following quench cool. Porosity measurements found concomitant increases in the surface area of the porous cake structure but a reduction in total pore volume. We propose that slow reconstitution results from either closed pores or small pores impeding the penetration of water into the lyophilized cake.


Beech, K. E., Biddlecombe, J. G., van der Walle, C. F., Stevens, L. A., Rigby, S. P., Burley, J. C., …Allena, S. (2015). Insights into the influence of the cooling profile on the reconstitution times of amorphous lyophilized protein formulations. European Journal of Pharmaceutics and Biopharmaceutics, 96, 247-254.

Journal Article Type Article
Acceptance Date Jul 31, 2015
Online Publication Date Aug 4, 2015
Publication Date Oct 1, 2015
Deposit Date Sep 15, 2017
Publicly Available Date Feb 5, 2019
Print ISSN 0939-6411
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 96
Pages 247-254
Public URL
Publisher URL


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