Dual Functionality of Poloxamer 188 in Freeze-Dried Protein Formulations: A Stabilizer in Frozen Solutions and a Bulking Agent in Lyophiles

Jinghan Li, Bhushan Munjal, Chaowang Zeng, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

Abstract

Poloxamer 188 (P188) was hypothesized to be a dual functional excipient, (i) a stabilizer in frozen solution to prevent ice-surface-induced protein destabilization and (ii) a bulking agent to provide elegant lyophiles. Based on X-ray diffractometry and differential scanning calorimetry, sucrose, in a concentration-dependent manner, inhibited P188 crystallization during freeze-drying, while trehalose had no such effect. The recovery of lactate dehydrogenase (LDH), the model protein, was evaluated after reconstitution. While low LDH recovery (∼60%) was observed in the lyophiles prepared with P188, the addition of sugar improved the activity recovery to >85%. The secondary structure of LDH in the freeze-dried samples was assessed using infrared spectroscopy, and only moderate structural changes were observed in the lyophiles formulated with P188 and sugar. Thus, P188 can be a promising dual functional excipient in freeze-dried protein formulations. However, P188 alone does not function as a lyoprotectant and needs to be used in combination with a sugar.

Original languageEnglish (US)
Pages (from-to)2555-2564
Number of pages10
JournalMolecular pharmaceutics
Volume21
Issue number5
DOIs
StatePublished - May 6 2024

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society.

Keywords

  • X-ray diffractometry
  • conformational stability
  • differential scanning calorimetry
  • freeze-drying
  • lactate dehydrogenase
  • poloxamer
  • protein activity
  • protein formulation
  • surfactant

MRSEC Support

  • Shared

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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