title: Investigation of PEG crystallization in frozen PEG-sucrose-water solutions. I. Characterization of the nonequilibrium behavior during freeze-thawing.
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 degrees C at 5 degrees C/min and heated to 25 degrees C at 2 degrees C/min in a differential scanning calorimeter. Annealing was performed at temperatures ranging from -50 to -20 degrees 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 degrees C. In unannealed systems with a fixed sucrose concentration (10%, w/v), the T'g decreased from -35 to -48 degrees C when PEG concentration was increased from 1% to 20% (w/v). On annealing at -25 degrees 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 <or=-40 degrees 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 degrees C when sucrose concentration was increased from 5% to 50%, w/v. As the annealing time increased (at -25 degrees C), the T'g approached that of a sucrose-water system, reflecting progressive PEG crystallization. A second glass transition at approximately -65 degrees C was evident in unannealed systems [10%, w/v sucrose and 10 (or 20%), w/v PEG] cooled to -100 degrees C. Investigation of the nonequilibrium behavior of frozen PEG-sucrose-water ternary system revealed phase separation in the freeze-concentrate. Annealing facilitated PEG crystallization.
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: D003080:Cold Temperature; D003460:Crystallization; D004304:Dosage Forms; D005615:Freezing; D007053:Ice; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D012996:Solutions; D013395:Sucrose / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction; D014965:X-Rays
chemical_list: D004304:Dosage Forms; D007053:Ice; D012996:Solutions; D014867:Water; D011092:Polyethylene Glycols; D013395:Sucrose