Heczko Dawid, Jurkiewicz Karolina, Grelska Joanna, Kamiński Kamil, Paluch Marian, Kamińska Ewa
Department of Pharmacognosy and Phytochemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1, 41-500 Chorzów, Poland.
J Phys Chem B. 2020 Dec 31;124(52):11949-11961. doi: 10.1021/acs.jpcb.0c08083. Epub 2020 Dec 16.
Dielectric studies under various temperature () and pressure () conditions on five active pharmaceutical ingredients (APIs) with antifungal properties-itraconazole (ITZ), posaconazole (POS), terconazole (TER), ketoconazole (KET), and fluconazole (FLU)-were carried out. We have thoroughly studied the connection between the pressure coefficient of the glass transition temperature (d/d) and the activation volume of both relaxation modes (Δ, Δ) with respect to the molecular weight () or molar volume () in these systems. Besides, high pressure data revealed that the time scale separation between and δ- or α'-processes increases with pressure in ITZ and TER. What is more, the activation entropy, which is a measure of cooperativity, calculated from the Eyring model for the secondary (β)-relaxation in ITZ and POS, increased and decreased, respectively, in the compressed samples. To understand these peculiar results, we have carried out X-ray diffraction (XRD) measurements on the pressure-densified glasses and found that pressure may induce frustration in molecular organization and destroy the medium-range order while enhancing the short-range correlations between molecules. This finding allowed us to conclude that varying molecular spatial arrangement is responsible for the extraordinary dynamical behavior of ITZ, POS, and TER at high pressure.
在不同温度（）和压力（）条件下，对五种具有抗真菌特性的活性药物成分（API）——伊曲康唑（ITZ）、泊沙康唑（POS）、特康唑（TER）、酮康唑（KET）和氟康唑（FLU）——进行了介电研究。我们深入研究了这些体系中玻璃化转变温度的压力系数（d/d）与两种弛豫模式的活化体积（Δ，Δ）相对于分子量（）或摩尔体积（）之间的关系。此外，高压数据表明，在ITZ和TER中，与δ-或α'-过程之间的时间尺度分离随压力增加。更重要的是，根据Eyring模型计算的ITZ和POS中二级（β）弛豫的活化熵（衡量协同性的指标），在压缩样品中分别增加和减少。为了理解这些奇特的结果，我们对压力致密化玻璃进行了X射线衍射（XRD）测量，发现压力可能会导致分子组织中的受挫，并破坏中程有序，同时增强分子间的短程相关性。这一发现使我们得出结论，分子空间排列的变化是导致ITZ、POS和TER在高压下具有非凡动力学行为的原因。
