Phase behavior of poloxamer 188 in frozen aqueous solutions - Influence of processing conditions and cosolutes.

The aim of the study is to investigate the thermal behavior of poloxamer 188 (P188) in binary (P188-water) and ternary (P188-trehalose-water) solutions during freezing and thawing. The thermal behavior of P188 in frozen (binary and ternary) systems was characterized by differential scanning calorimetry (DSC) and low-temperature X-ray powder diffractometry (XPRD) as a complementary technique. The influence of processing conditions (cooling rate, annealing) and a noncrystallizing co-solute (addition of trehalose) on the behavior of P188 was evaluated during freezing as well as thawing. In rapidly cooled (10 °C/min) aqueous binary solutions, P188 (10% w/v) was retained in the amorphous state. At slower cooling rates (0.5-5 °C/min), the extent of crystallization depended on the cooling rate. In ternary P188-trehalose-water systems (P188 4% w/v, trehalose 0-10% w/v), a concentration dependent inhibition of P188 crystallization was observed with increasing trehalose concentration. However, irrespective of trehalose concentration, annealing resulted in P188 crystallization. The presence of trehalose as well as the processing conditions (cooling rate and annealing) influenced the physical state of P188 at different stages of freezing and thawing. As the cooling rate decreased, the extent of P188 crystallization progressively increased. In presence of trehalose (≥4.0% w/v) crystallization of P188 (4.0% w/v) was inhibited and this effect could be reversed by annealing. Depending on the intended application, the physical form of P188 could be modulated, by annealing even in presence of a noncrystallizing solute.