Investigation of PEG crystallization in frozen PEG-sucrose-water solutions: II. Characterization of the equilibrium behavior during freeze-thawing

Bakul S. Bhatnagar, Susan M. Martin, Dirk L. Teagarden, Evgenyi Shalaev, Raj Suryanarayanan

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Our objective was to characterize, by DSC and XRD, the equilibrium thermal behavior of frozen aqueous solutions containing polyethylene glycol (PEG) and sucrose. Aqueous solutions of (i) PEG (2.5-50% w/w), (ii) sucrose (10% w/v) with different concentrations of PEG (1-20% w/v), and (iii) PEG (2% or 10% w/v) with different concentrations of sucrose (2-20% w/v), were cooled to -70°C at 5°C/min and heated to 25°C at 2°C/min in a DSC. Annealing was performed for 2 or 6 h at temperatures, ranging from -50 to -20°C. Experiments under similar conditions, on select compositions, were also performed in a powder X-ray diffractometer. Two endotherms, observed during heating of a frozen PEG solution (10% w/v), were attributed to PEG-ice eutectic melting and ice melting, and were confirmed by XRD. At higher PEG concentrations (≥37.5% w/w), only the endotherm attributed to the PEG-ice eutectic melting was observed. Inclusion of sucrose decreased both PEG-ice melting and ice melting temperatures. In unannealed systems with a fixed sucrose concentration (10% w/v), the PEG-ice melting event was not observed at PEG concentration ≤5% w/v. Annealing for 2-6 h facilitated PEG crystallization. In unannealed systems with a fixed PEG concentration (10% w/v), an increase in the sucrose concentration increased the devitrification but decreased the PEG-ice melting temperature. The PEG-ice melting temperatures obtained by DSC and XRD were in good agreement. In ternary systems at a fixed PEG to sucrose ratio, the $T_{\rm g}^\prime$ as well as the PEG-ice melting temperature were unaffected by the total solute concentration. XRD confirmed the absence of a PEG-sucrose-ice ternary eutectic. When the PEG to sucrose ratio was systematically varied, the PEG-ice and ice melting temperatures decreased with an increase in the sucrose concentration. However, at a fixed PEG to sucrose ratio, the PEG-ice melting temperature, was unaffected by the total solute concentration.

Original languageEnglish (US)
Pages (from-to)4510-4524
Number of pages15
JournalJournal of Pharmaceutical Sciences
Volume99
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • Cryo-protectant
  • Crystallization
  • Eutectic melting
  • Freeze-concentration
  • Freeze-drying
  • Freeze-thawing
  • Freezing point depression
  • Low temperature XRD
  • Lyophilization
  • PEG
  • Sucrose
  • Ternary phase diagram

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