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FTIR and nDSC as Analytical Tools for High-Concentration Protein Formulations

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Purpose

The aim of the study is to evaluate Fourier-transform infrared spectroscopy (FTIR) as an analytical tool for high-concentrated protein formulations.

Methods

FTIR is used to determine the melting temperature (T m (FTIR)) of various proteins, such as bovine serum albumin (BSA), immunoglobulin (IgG1), β-lactoglobulin (β-LG), and lysozyme (HEWL), at different protein concentrations (5–100 mg/mL), where four data interpretation methods are discussed. The obtained T m (FTIR) values are further compared to the T m measured by the nanodifferential scanning calorimetry (nDSC) technique.

Results

The T m (FTIR) values of IgG1 and β-LG showed strong consistency and corresponded to the nDSC results irrespective of the method of data interpretation and the protein concentration applied. In contrast, the T m (FTIR) of BSA and HEWL is characterized by significant deviations. Only the midpoint of the second-derivative intensity–temperature curve of the intermolecular β-sheet mode measured at a concentration of 100 mg/mL is consistent with the nDSC results.

Conclusions

Determination of a T m (FTIR) is feasible by the midpoint of the intensity–temperature plot of the arising intermolecular β-sheet band. More significant results are obtained for proteins, which are predominantly composed of intramolecular β-sheet elements as well as at higher protein concentrations. A further study was started to assess the predictability of long-term protein stability by T m (FTIR).

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Acknowledgments

The authors thank Claudia Borst and Franziska Huber for their assistance in the experimental work.

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  1. Hanns-Christian Mahler

    Present address: F. Hoffmann-La Roche Ltd, Grenzacherstrasse 170, CH-4070, Basel, Switzerland

Authors and Affiliations

  1. Merck KGaA, Global Pharmaceutical Development, Darmstadt, Germany

    Susanne Matheus & Hanns-Christian Mahler

  2. Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University Munich, Munich, Germany

    Wolfgang Friess

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  1. Susanne Matheus
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  2. Wolfgang Friess
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Correspondence to Hanns-Christian Mahler.

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Matheus, S., Friess, W. & Mahler, HC. FTIR and nDSC as Analytical Tools for High-Concentration Protein Formulations. Pharm Res 23, 1350–1363 (2006). https://doi.org/10.1007/s11095-006-0142-8

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