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Article

Be Aggressive! Amorphous Excipients Enabling Single-Step Freeze-Drying of Monoclonal Antibody Formulations

1
Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland
2
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland
3
Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(11), 616; https://doi.org/10.3390/pharmaceutics11110616
Received: 10 October 2019 / Revised: 30 October 2019 / Accepted: 12 November 2019 / Published: 17 November 2019
(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying)
Short freeze-drying cycles for biopharmaceuticals are desirable. Formulations containing an amorphous disaccharide, such as sucrose, are prone to collapse upon aggressive primary drying at higher shelf temperature. We used 2-hydroxypropyl-betacyclodextrin (HPBCD) in combination with sucrose and polyvinylpyrrolidone (PVP) to develop an aggressive lyophilization cycle for low concentration monoclonal antibody (mAb) formulations. Glass transition temperature and collapse temperature of the formulations were determined, and increasingly aggressive cycle parameters were applied. Using a shelf temperature of +30 °C during primary drying, the concept of combining sublimation and desorption of water in a single drying step was investigated. Cake appearance was evaluated visually and by micro-computed tomography. Lyophilisates were further analyzed for reconstitution time, specific surface area, residual moisture, and glass transition temperature. We demonstrated the applicability of single-step freeze-drying, shortening the total cycle time by 50% and providing elegant lyophilisates for pure HPBCD and HPBCD/sucrose formulations. HPBCD/PVP/sucrose showed minor dents, while good mAb stability at 10 mg/mL was obtained for HPBCD/sucrose and HPBCD/PVP/sucrose when stored at 40 °C for 3 months. We conclude that HPBCD-based formulations in combination with sucrose are highly attractive, enabling aggressive, single-step freeze-drying of low concentration mAb formulations, while maintaining elegant lyophilisates and ensuring protein stability at the same time. View Full-Text
Keywords: glass transition; collapse; freeze-drying; cyclodextrin; antibody; cycle optimization; single-step freeze-drying glass transition; collapse; freeze-drying; cyclodextrin; antibody; cycle optimization; single-step freeze-drying
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MDPI and ACS Style

Haeuser, C.; Goldbach, P.; Huwyler, J.; Friess, W.; Allmendinger, A. Be Aggressive! Amorphous Excipients Enabling Single-Step Freeze-Drying of Monoclonal Antibody Formulations. Pharmaceutics 2019, 11, 616. https://doi.org/10.3390/pharmaceutics11110616

AMA Style

Haeuser C, Goldbach P, Huwyler J, Friess W, Allmendinger A. Be Aggressive! Amorphous Excipients Enabling Single-Step Freeze-Drying of Monoclonal Antibody Formulations. Pharmaceutics. 2019; 11(11):616. https://doi.org/10.3390/pharmaceutics11110616

Chicago/Turabian Style

Haeuser, Christina, Pierre Goldbach, Joerg Huwyler, Wolfgang Friess, and Andrea Allmendinger. 2019. "Be Aggressive! Amorphous Excipients Enabling Single-Step Freeze-Drying of Monoclonal Antibody Formulations" Pharmaceutics 11, no. 11: 616. https://doi.org/10.3390/pharmaceutics11110616

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