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M. Sc. Tanja Stolzke

M. Sc. Tanja Stolzke Foto von M. Sc. Tanja Stolzke

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Fakultät Bio- und Chemieingenieurwesen
Emil-Figge-Str. 70
44227 Dortmund

Raum G2-514

Stabilization and Aggregation of Biopharmaceuticals

Abstract:

The development of protein formulations for administration of monoclonal antibodies (mAbs) is an important and growing field in pharmaceutical biotechnology [1]. The low solubilities achieved in state of the art formulations commonly only allows their administration via intravenous injection [1]. An increase in protein concentration, which enables the subcutaneous administration, requires the addition of suitable excipients / excipient mixtures to stabilize the protein in solution and increase solubility. A method for their identification, furthermore delivering a mechanistic understanding, will be identified within this work.

 

Description:

In order to engineer high-concentration protein formulations (HCPFs), the addition of excipients is typically required to increase the protein solubility and stability. Frequently used excipients in the (bio)-pharmaceutical industry include: amino acids, salts, sugars, polymers, and surfactants that already have a Food and Drug Administration (FDA) approval [1,2]. The selection of suitable excipients for development of HCPFs is commonly performed on the basis of heuristics (“trial and error”) and is carried out by high-throughput screening methods [3]. Within this work, suitable excipients and their potential will be identified based on a mechanistic understanding of the underlying molecular interactions. Based on the investigations and characterization of interactions (e.g. light-scattering analytics, physical models), it’s the aim of this work to predict thermodynamic properties of aqueous protein solutions. This will lead to a reduction in time and experimental effort in investigations of suitable protein formulations.

 

References:

[1] S. Mitragotri, P. A. Burke, R. Langer:
"Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies"
Nat.Rev. Drug Discov., 13, (9), 655-72, 2014
10.1038/nrd4363
[2] V. Kumar, N. Dixit, L. L. Zhou, W. Fraunhofer:
"Impact of short range hydrophobic interactions and long range electrostatic forces on the aggregation kinetics of a monoclonal antibody and a dual-variable domain immunoglobulin at low and high concentrations"
Int. J. Pharm., 421, (1), 82-93, 2011
10.1016/j.ijpharm.2011.09.017
[3]

M. A. H. Capelle, R. Gurny, T. Arvinte:
"High troughput screening of protein formulation stability: Practical considerations"
Europ. J. Pharm. Biopharm., 65, 131-148, 2007
10.1016/j.ejpb.2006.09.009

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