title: Investigation of PEG crystallization in frozen PEG-sucrose-water solutions: II. Characterization of the equilibrium behavior during freeze-thawing.
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' g 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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, 308 Harvard St. SE, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Bakul S
authors.initials: BS
authors.lastname: Bhatnagar
authors.forename: Susan M
authors.initials: SM
authors.lastname: Martin
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Teagarden
authors.forename: Evgenyi Y
authors.initials: EY
authors.lastname: Shalaev
authors.forename: Raj
authors.initials: R
authors.lastname: Suryanarayanan
mesh_terms: D003460:Crystallization; D005615:Freezing; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D013395:Sucrose / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D011092:Polyethylene Glycols; D013395:Sucrose