Phase Behavior of Poloxamer 188 Aqueous Solutions at Subzero Temperatures: A Neutron and X‑ray Scattering Study

Phase transitions of poloxamer 188 (P188) aqueous solutions at freezing temperatures are investigated using small-angle neutron scattering (SANS) and small- and wide-angle X-ray scatterings (SAXS and WAXS). It is shown that P188 solution (10%) undergoes the following sequence of phase transitions during cooling from 25 to −150 °C: micelle solution, solution of monomers, two-phase mixture of liquid crystalline mesophase + ice, and finally crystalline P188 + ice. Formation of the liquid crystalline phase during freezing is likely to be triggered by water freezing to ice and corresponding freeze concentration of the remaining solution. During heating of the frozen solutions, the sequence of the phase transitions is reversed: crystalline P188 + ice, liquid crystalline mesophase + ice, monomer solution + ice, monomer solution, and finally micelle solution. Similar phase transitions are detected for dilute solutions of P188 (1%) except that micelle formation is not observed at 25 °C, consistent with the literature reported critical micelle concentration (CMC) at this temperature. The present study provides new insight into P188 aqueous solutions at freezing temperatures and has practical implications on the design and development of pharmaceutical formulations.