Abstract
Our objective was to characterize the nonequilibrium thermal behavior of frozen aqueous solutions containing PEG and sucrose. Aqueous solutions of (i) sucrose (10%, w/v) with different concentrations of PEG (1-20%, w/v), and (ii) PEG (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 differential scanning calorimeter. Annealing was performed at temperatures ranging from -50 to -20°C for 2 or 6 h. Similar experiments were also performed in the low-temperature stage of a powder X-ray diffractometer. A limited number of additional DSC experiments were performed wherein the samples were cooled to -100°C. In unannealed systems with a fixed sucrose concentration (10%, w/v), the T′g decreased from -35 to -48°C when PEG concentration was increased from 1% to 20% (w/v). On annealing at -25°C, PEG crystallized. This was evident from the increase in T′g and the appearance of a secondary melting endotherm in the DSC. Low-temperature XRD provided direct evidence of PEG crystallization. Annealing at temperatures ≤40°C did not result in crystallization and a devitrification event was observed above the T′g. In unannealed systems with a fixed PEG concentration (10%, w/v), the T′g increased from -50 to -40°C when sucrose concentration was increased from 5% to 50%, w/v. As the annealing time increased (at -25°C), the T′g approached that of a sucrose-water system, reflecting progressive PEG crystallization. A second glass transition at ∼ -65°C was evident in unannealed systems [10%, w/v sucrose and 10 (or 20%), w/v PEG] cooled to -100°C. Investigation of the nonequilibrium behavior of frozen PEG-sucrose-water ternary system revealed phase separation in the freeze-concentrate. Annealing facilitated PEG crystallization.
Original language | English (US) |
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Pages (from-to) | 2609-2619 |
Number of pages | 11 |
Journal | Journal of Pharmaceutical Sciences |
Volume | 99 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2010 |
Bibliographical note
Funding Information:The XRD experiments were performed at the University of Minnesota I. T. Characterization Facility, which receives partial support from the NSF through the NNIN program. We thank Linda Sauer and Ryan Wold for their assistance with low-temperature XRD experiments. Julie Stambek from Pfizer Global Biologics is acknowledged for performing the density measurements on PEG–water and PEG–sucrose–water systems.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
Keywords
- Cryoprotectant
- Crystallization
- Eutectic melting
- Freeze-concentration
- Freeze-drying
- Freeze-thawing
- Low-temperature XRD
- Lyophilization
- PEG
- Phase separation
- Sucrose
- Ternary phase diagram