Solute Diffusion in Styrenic Triblock Copolymer Organogels

Gels composed of styrenic triblock copolymer and aliphatic solvent have been recently considered for use in transdermal drug delivery systems (TDDSs) due in part to their adhesive properties and nonpolar chemistry. Past research conducted on these block copolymer organogels has provided some formulation strategies to optimize their adhesiveness, drug retention, in vitro drug release, and in vivo delivery performance. However, the aforementioned studies' characterization of extrinsic properties and use of empirical modeling limit the generalizability of their outlined strategies. The current study presents solute diffusivity-an intrinsic material property-for various copolymer organogels including those with different copolymer molecular weights and concentrations, as well as several unique solutes. Furthermore, the gathered data sets are fitted with a theoretical model that accounts for the nanostructure of organogels including their impenetrable discrete domains (polystyrene) and continuous phase comprising solvated midblocks (poly-[ethylene-propylene] or poly-[ethylene-butylene]) and gel solvent. This model yields the hydrodynamic radius of the penetrant (i.e., solute molecules or aggregates) and its average rate of movement through a given gel. Interpretation of diffusivity values and model fit parameters suggests that copolymer concentration has a considerably stronger effect on solute diffusion than copolymer molecular weight. For example, increasing concentration from 5 wt% to 20 wt% yields a 50% reduction in solute diffusivity whereas molecular weight (at a fixed concentration) is observed to have a negligible impact. Our findings also highlight that solute aggregation behavior must be carefully considered when designing organogel-based TDDSs. The hydrodynamic radii of solutes employed do not correlate with their molecular weights (OA: 282.5 g/mol, 0.3 nm; SMO: 428.6 g/mol, 0.7 nm; AOT: 444.6 g/mol, 2.6 nm; STO: 957.5 g/mol, 0.8 nm), which stems from differing self-assembly behavior in the gel solvent. We anticipate that the presented results and analysis will enable more effective bottom-up design of block copolymer organogels for TDDSs.