Effects of Sugars and Polymers on Crystallization of Poly(ethylene glycol) in Frozen Solutions: Phase Separation Between Incompatible Polymers |
| |
Authors: | Izutsu Ken-ichi Yoshioka Sumie Kojima Shigeo Randolph Theodore W Carpenter John F |
| |
Institution: | (1) National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158, Japan;(2) Department of Chemical Engineering, University of Colorado, Boulder, Colorado;(3) School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado |
| |
Abstract: | Purpose. This study examined the effect of third components (low-molecular-weight saccharides and polymers) on the crystallization of poly(ethylene) glycol (PEG) in frozen solutions, focusing on the relationship between their crystallization-inhibiting ability and molecular compatibility.
Methods. Effects of sugars and polymers on the crystallization of PEG 3000 in frozen solution were monitored by differential scanning calorimetry (DSC). Pulsed-NMR was employed to monitor the molecular mobility of water and solutes in the frozen solutions. Miscibility between PEG and third components in aqueous solution was estimated from the lowering of cloud point of PEG 20,000. Thermal analysis of frozen solutions containing some non-crystallizing solutes was used to examine the possibility of phase separation in frozen solutions.
Results. Some sugars and polymers inhibited the crystallization of PEG and formed practically stable amorphous phases among ice crystals. The mobility of solute molecules in the amorphous phase increased above the softening temperature of maximally concentrated solutions (Ts), whereas that of water molecules appeared at a lower temperature. Mono- and disaccharides that are relatively less miscible with PEG in solution inhibit PEG crystallization to a lesser degree. Two Ts regions were observed in frozen solutions containing both polyvinylpyrrolidone (PVP) and dextran, at much lower concentrations than those causing aqueous two-phase separation at ambient temperatures.
Conclusions. Ice crystallization raises the concentration of solutes in the remaining solution, which can lead to phase separation in the amorphous phase. Molecular compatibility between components is an important factor determining their propensity to phase separate and crystallize. |
| |
Keywords: | frozen solution phase separation poly(ethylene glycol) crystallization molecular interaction |
本文献已被 SpringerLink 等数据库收录! |
|