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Surface Composition and Formulation Heterogeneity of Protein Solids Produced by Spray Drying

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Abstract

Purpose

The aim of this study is to determine the effects of saccharide-containing excipients on the surface composition of spray-dried protein formulations and their matrix heterogeneity.

Methods

Spray-dried formulations of myoglobin or bovine serum albumin (BSA) were prepared without excipient or with sucrose, trehalose, or dextrans. Samples were characterized by solid-state Fourier-transform infrared spectroscopy (ssFTIR), differential scanning calorimetry (DSC), size exclusion chromatography (SEC) and scanning electron microscopy (SEM). Protein surface coverage was determined by X-ray photoelectron spectroscopy (XPS), while conformational differences were determined by solid-state hydrogen/deuterium exchange with mass spectrometry (ssHDX-MS).

Results

Structural differences were exhibited with the inclusion of different excipients, with dextran formulations indicating perturbation of secondary structure. XPS indicated sucrose and trehalose reduced protein surface concentration better than dextran-containing formulations. Using ssHDX-MS, the amount of deuterium incorporation and populations present were the largest in the samples processed with dextrans. Linear correlation was found between protein surface coverage and ssHDX-MS peak area (R2 = 0.853) for all formulations with saccharide-containing excipients.

Conclusions

Lower molecular weight species of saccharides tend to enrich the particle surface and reduce protein concentration at the air-liquid interface, resulting in reduced population heterogeneity and improved physical stability, as identified by ssHDX-MS.

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Acknowledgments and Disclosures

This study was partially supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI132681 and R01AI146160. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA

    Nathan E. Wilson, Tarun Tejasvi Mutukuri, Lynne S. Taylor, Elizabeth M. Topp & Qi Tony Zhou

  2. Birck Nanotechnology Center, Purdue University, 1205 West State Street, West Lafayette, Indiana, 47907, USA

    Dmitry Y. Zemlyanov

Authors
  1. Nathan E. Wilson
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  2. Tarun Tejasvi Mutukuri
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  3. Dmitry Y. Zemlyanov
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  4. Lynne S. Taylor
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  5. Elizabeth M. Topp
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  6. Qi Tony Zhou
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Correspondence to Elizabeth M. Topp or Qi Tony Zhou.

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Wilson, N.E., Mutukuri, T.T., Zemlyanov, D.Y. et al. Surface Composition and Formulation Heterogeneity of Protein Solids Produced by Spray Drying. Pharm Res 37, 14 (2020). https://doi.org/10.1007/s11095-019-2738-9

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  • DOI: https://doi.org/10.1007/s11095-019-2738-9

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