The behaviour and control of Poloxamer activity in aqueous solution: polymer assembly, impact of bulk composition and tuneable nano formulation design

Objectives:
Biocompatible block copolymers, due to their amphiphilic nature, offer solutions to improve drug solubility, targeting, and stability in drug delivery. However, the design and application of these constructs require critical evaluation of the impact of bulk properties on the resultant architecture and assembly of these systems. Pharmaceutically relevant additives influence micellization in aqueous solutions through indirect (salts) or direct (surfactants, solvents, oils, drugs) interactions with copolymer chains, thereby controlling micelle formation and morphology due to their impact on fundamental properties such as critical micelle concentration, critical micelle temperature and phase transition temperatures. This article provides current insights into the behaviour of poloxamers, in aqueous solutions, to understand the impact of addition of bulk modifying excipients on polymer assembly, micellization, morphology and energetics to overcome the challenges presented by poorly soluble drugs.

Methods:
Web of Science (Clarivate) and PubMed scientific journal databases was searched with a focus on Poloxamer behaviour characterisation and activity in the presence of various pharmaceutically relevant excipients namely salts, surfactants, solvents, oils and active pharmaceutical ingredients.

Key Findings:
Poloxamer displays enhanced association activity (decrease in CMC/CMT) in the presence of various excipients through direct and indirect interactions with Poloxamer chains that influence its behaviour. There is a gap in the scope of research that describes the relevance of this enhanced activity for improving solubilisation of poorly water-soluble drugs, as the improvement is only implied and has not been experimentally demonstrated.

Conclusions:
Further studies to elucidate the significance this excipient driven enhanced Poloxamer activity presents for boosting poorly water-soluble drug solubilisation is required. There is a need to identify the significance of employing one excipient strategy on Poloxamer performance against the other, determine if there is synergy between the different influences exerted by different excipient groups as well as if there is any hierarchy among the excipients in exerting their influence. In addition, how this solubilisation behaviour changes as drug properties such as molecular weight and log-P vary should be included.