Mechanistic assessment and control of poloxamer activity: exploiting bulk hydration to maximise solubilisation capacity

Abstract Although literature describes pluronic micellisation behaviour in solution, it does not elucidate the associated solubilisation capacities achieved nor how this capacity changes with micellisation potential, particularly when considering the impact of changes in the composition of the bulk media. This study, for the first time, employed differential scanning calorimetry, supported by micrometric analysis and drug loading studies, to mechanistically investigate the behaviour and impact of bulk hydration on changes in polymer chain-bulk interactions of Pluronic F-127. Employing a model hydrophobic drug (1,6-Diphenyl-1,3,5-hexatriene (DPH)) and pharmaceutically relevant carbamazepine, Pluronic F-127 solubilisation activity was shown to significantly increase up to 18 folds once the threshold of 2.5 times its critical micellisation concentration (CMC) is crossed. Particle properties such as size, polydispersity and drug loading were studied to understand the relationship between polymer behaviour and drug solubilisation. This study provides a paradigm for controlling loading capacity of poorly soluble drugs, that can be carefully tuned through the selection of well hydrated excipients that indirectly influence polymer behaviour.