活性成分(AI)在聚合物固体分散体中的自扩散系数是生命科学合理配方设计的重要参数之一。在其应用温度范围内测量产品的此参数可以,然而,是难以实现和耗时的(由于扩散的缓慢动力学)。这项研究的目的是提供一个简单而省时的平台,用于根据Vrentas和Duda的自由体积理论(FVT)的修改版预测无定形和半结晶聚合物中的AI自扩散率[A.Mansuri,M.Völkel,T.费尔巴哈,J.温克,A.W.P.维米尔,W.Hoheisel,M.Thommes,改进的自由体积理论,用于无定形聚合物中小分子的自扩散,大分子。(2023)]。这项工作中讨论的预测模型需要纯组分性质作为其输入,并涵盖T<1.2Tg的近似温度范围,二元混合物的整个组成范围(只要存在分子混合物),和聚合物的整个结晶度范围。在这种情况下,AIs吡虫啉的自扩散系数,吲哚美辛,和溴氰菊酯在聚乙烯吡咯烷酮中的预测,聚乙烯吡咯烷酮/醋酸乙烯酯,聚苯乙烯,聚乙烯,和聚丙烯。结果突出了固体分散体的动力学脆性对分子迁移的深远重要性;尽管聚合物的分子量增加,但在某些情况下可能需要更高的自扩散系数。我们在玻璃形成剂的异质动力学理论的背景下解释了这一观察[医学博士Ediger,过冷液体中的空间非均质动力学,安努。Rev.Phys.Chem.51(2000)99-128],将其归因于脆性聚合物中“流体样”移动区域的更强存在,为分散体内的AI扩散提供了便利的途径。改进的FVT进一步允许识别一些结构和热物理材料性质对具有聚合物的二元分散体中的AI的平移迁移率的影响。此外,通过进一步考虑扩散路径的曲折度和无定形相和结晶相界面处的链固定,可以估计半结晶聚合物的自扩散系数。
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 self-diffusivity 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. Völkel, 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 semi-crystalline 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.