Inhomogeneous Distribution of Components in Solid Protein Pharmaceuticals: Origins, Consequences, Analysis, and Resolutions

Khanh T. T. Nguyen, Henderik W. Frijlink, Wouter L. J. Hinrichs*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

1 Citation (Scopus)
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Abstract

Successful development of stable solid protein formulations usually requires the addition of one or several excipients to achieve optimal stability. In these products, there is a potential risk of an inhomogeneous distribution of the various ingredients, specifically the ratio of protein and stabilizer may vary. Such inhomogeneity can be detrimental for stability but is mostly neglected in literature. In the past, it was challenging to analyze inhomogeneous component distribution, but recent advances in analytical techniques have revealed new options to investigate this phenomenon. This paper aims to review fundamental aspects of the inhomogeneous distribution of components of freeze-dried and spray-dried protein formulations. Four key topics will be presented and discussed, including the sources of component inhomogeneity, its consequences on protein stability, the analytical methods to reveal component inhomogeneity, and possible solutions to prevent or mitigate inhomogeneity.

Original languageEnglish
Pages (from-to)134-153
Number of pages20
JournalJournal of Pharmaceutical Sciences
Volume109
Issue number1
DOIs
Publication statusPublished - Jan-2020

Keywords

  • phase separation(s)
  • freeze-drying
  • spray drying
  • protein formulation(s)
  • stability
  • solid-state
  • analysis
  • imaging method(s)
  • spectroscopy
  • AMORPHOUS PHASE-SEPARATION
  • HUMAN GROWTH-HORMONE
  • NEAR-INFRARED SPECTROSCOPY
  • GLASS-TRANSITION TEMPERATURES
  • DRYING-INDUCED VARIATIONS
  • ATOMIC-FORCE MICROSCOPY
  • RAY-POWDER DIFFRACTION
  • STORAGE STABILITY
  • LACTATE-DEHYDROGENASE
  • FREEZE-CONCENTRATION

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