Predicting self-diffusion coefficients in semi-crystalline and amorphous solid dispersions using free volume theory

The self-diffusion coefficient of active ingredients (AI) in polymeric solid dispersions is one of the essential parameters for the rational formulation design in life sciences. Measuring this parameter for products in their application temperature range can, however, be difficult to realise and time-consuming (due to the slow kinetics of diffusion). The aim of this study is to present a simple and time-saving platform for predicting the AI selfdiffusivity in amorphous and semi-crystalline polymers on the basis of a modified version of Vrentas' and Duda's free volume theory (FVT) [A. Mansuri, M. Vo & BULL;lkel, T. Feuerbach, J. Winck, A.W.P. Vermeer, W. Hoheisel, M. Thommes, Modified free volume theory for self-diffusion of small molecules in amorphous polymers, Macromolecules. (2023)]. The predictive model discussed in this work requires pure-component properties as its input and covers the approximate temperature range of T < 1.2 Tg, the whole compositional range of the binary mixtures (as long as a molecular mixture is present), and the whole crystallinity range of the polymer. In this context, the self-diffusion coefficients of the AIs imidacloprid, indomethacin, and deltamethrin were predicted in polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate, polystyrene, polyethylene, and polypropylene. The results highlight the profound importance of the kinetic fragility of the solid dispersion on the molecular migration; a property which in some cases might entail higher self-diffusion coefficients despite an increase in the molecular weight of the polymer. We interpret this observation within the context of the theory of heterogeneous dynamics in glass-formers [M.D. Ediger, Spatially heterogeneous dynamics in supercooled liquids, Annu. Rev. Phys. Chem. 51 (2000) 99-128] by attributing it to the stronger presence of fluid-like mobile regions in fragile polymers offering facilitated routes for the AI diffusion within the dispersion. The modified FVT further allows for identifying the influence of some structural and thermophysical material properties on the translational mobility of AIs in binary dispersions with polymers. In addition, estimates of self-diffusivity in semicrystalline polymers are provided by further accounting for the tortuosity of the diffusion paths and the chain immobilisation at the interface of the amorphous and crystalline phases.

Automated summary

This study presents a simple and time-saving method for predicting the self-diffusion coefficient of active ingredients in polymeric solid dispersions. The predictive model based on modified versions of Vrentas' and Duda's free volume theory covers a wide temperature range and compositional range in binary mixtures. The results highlight the importance of kinetic fragility on molecular migration and offer insights into the influence of material properties on translational mobility.