Röwekamp Lara, Moch Kevin, Gainaru Catalin, Böhmer Roland
Fakultät Physik, Technische Universität Dortmund, 44221 Dortmund, Germany.
Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.
Mol Pharm. 2022 May 2;19(5):1586-1597. doi: 10.1021/acs.molpharmaceut.2c00077. Epub 2022 Apr 11.
Acetaminophen, nicotine, and lidocaine hydrochloride were investigated in their deeply supercooled liquid states using oscillatory shear rheology. The mechanical spectra of these drugs are presented in modulus, compliance, as well as fluidity formats. Their frequency profiles can be described via models adapted from the field of charge transport. Inspired by the success of this approach, the Barton-Nakajima-Namikawa relation, best known from the same field, was also tested. When adapted to rheology, this approach interrelates static and dynamic characteristics of viscous flow and was found to work excellently. The temperature dependence of the characteristic shear frequencies was checked against the shoving model, which relates them to the temperature-dependent instantaneous shear modulus and acceptable agreement was found. Combined with shear mechanical literature data on ibuprofen and indomethacin, a modified version of the phenomenological model by Gemant, DiMarzio, and Bishop (GDB) was employed to successfully predict the shape and amplitude of the dielectric spectra for all studied liquids, except for lidocaine hydrochloride. For the latter, the modified GDB model is suggested to aid in mapping out the reorientational part of the dielectric response, while the experimental results are strongly superimposed by ionic conduction phenomena. The reverse transformation, the calculation of rheological spectra based on dielectric ones, is also successfully demonstrated. For the example of acetyl salicylic acid, it is shown how dielectric spectra can be used to even predict rheological ones. The limits of the central parameter governing these mutual transformations, the electroviscoelastic material constant, and indications for its correlation with the dielectric relaxation strength are discussed. For pharmaceuticals characterized by a strong dynamical decoupling of the electrical from the mechanical degrees of freedom, the modified GDB model is not expected to be applicable.
使用振荡剪切流变学研究了对乙酰氨基酚、尼古丁和盐酸利多卡因在深度过冷液态下的情况。这些药物的力学谱以模量、柔量以及流动性形式呈现。它们的频率分布可以通过电荷传输领域的适配模型来描述。受此方法成功的启发，同一领域中最著名的巴顿 - 中岛 - 并川关系也进行了测试。当应用于流变学时，这种方法将粘性流动的静态和动态特性相互关联，并且发现效果极佳。根据推挤模型检查了特征剪切频率的温度依赖性，该模型将它们与温度依赖性瞬时剪切模量相关联，发现两者吻合良好。结合布洛芬和吲哚美辛的剪切力学文献数据，采用了由杰曼特、迪马尔齐奥和毕晓普（GDB）提出的现象学模型的修改版本，成功预测了所有研究液体（除盐酸利多卡因外）的介电谱的形状和幅度。对于后者，建议使用修改后的GDB模型来辅助描绘介电响应的重取向部分，而实验结果强烈叠加了离子传导现象。还成功演示了反向转换，即基于介电谱计算流变谱。以乙酰水杨酸为例，展示了如何使用介电谱来预测流变谱。讨论了控制这些相互转换的核心参数——电粘弹性材料常数的局限性，以及其与介电弛豫强度相关性的指示。对于以电学与力学自由度之间强烈动态解耦为特征的药物，预计修改后的GDB模型不适用。
