Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 60-780 Poznan, Poland.
Department of Experimental and Clinical Pharmacology, Medical College of Rzeszow University, The University of Rzeszow, 35-310 Rzeszow, Poland; Interdyscyplinarny Center Preclinical and Clinical Research, The University of Rzeszow, 36-100 Werynia, Poland.
J Pharm Biomed Anal. 2022 Aug 5;217:114822. doi: 10.1016/j.jpba.2022.114822. Epub 2022 May 7.
The thermal behaviour of crystalline and amorphous carvedilol (CAR) phases was studied by advanced thermal analysis using Quantum Design Physical Property Measurement System and Differential Scanning Calorimetry. Theoretical functions describing crystalline carvedilol heat capacity at low temperatures and the Debye-Einstein function for high temperatures were obtained. Based on the experimental heat capacity values, solid and liquid baselines were established, and the state functions (H, S, G) for solid and liquid states were calculated. A comprehensive characterization of melting and glass transition processes was obtained. CAR is easily amorphizable by cooling the liquid. The residual entropy, which quantifies the extent of frozen-in disorder in the amorphous solid, for glassy CAR was estimated as 51 J·mol·K. The Kauzmann temperature (T) was estimated based on enthalpy and entropy. Molecular motions in the amorphous phase were also studied. The activation energy for structural relaxation (E = 539 kJ·mol) and fragility parameter (m = 91) were obtained from the non-isothermal physical ageing. The isothermal physical ageing kinetics of amorphous CAR was studied by applying Kohlrausch-Williams-Watts (KWW) model. The mean molecular relaxation time constant (τ = 117 min) and relaxation constant (β = 0.33) were obtained. CAR was classified as a fragile glass-former. Furthermore, τ constant for samples aged at 303.15 K is very low, thus, the physical ageing will occur during the short- and long-term storage of amorphous CAR, potentially changing its physicochemical properties during the ageing process. However, the results of molecular mobility studies (high molecular motions) show that the relationship between molecular motions in a glassy solid and its tendency to crystallization does not seem to follow an expected pattern, i.e., no crystallization occurred by thermal treatment of glassy, supercooled liquid and liquid phases of CAR as one would expect. Modern calorimetry and quantitative thermal analysis provided the fundamental kinetic and thermodynamic information about the crystalline and amorphous states of CAR.
采用先进的热分析方法，使用量子设计物理性能测量系统和差示扫描量热法研究了结晶型和非晶型卡维地洛（CAR）的热行为。得到了描述低温下结晶型卡维地洛热容的理论函数和高温下德拜-爱因斯坦函数。基于实验热容值，建立了固、液基线，并计算了固、液态的状态函数（H、S、G）。获得了熔融和玻璃化转变过程的综合特征。通过冷却液体，CAR 很容易非晶化。对于玻璃态 CAR，估计其残余熵为 51 J·mol·K，该熵量化了非晶固体中冻结无序的程度。根据焓和熵估计了卡扎曼温度（T）。还研究了非晶相中的分子运动。通过非等温物理老化获得了结构弛豫的活化能（E=539 kJ·mol）和脆性参数（m=91）。通过应用 Kohlrausch-Williams-Watts（KWW）模型研究了非晶态 CAR 的等温物理老化动力学。得到了平均分子弛豫时间常数（τ=117 min）和弛豫常数（β=0.33）。CAR 被归类为脆性玻璃形成体。此外，在 303.15 K 老化的样品中，τ 常数非常低，因此，在非晶态 CAR 的短期和长期储存过程中会发生物理老化，在老化过程中其物理化学性质可能会发生变化。然而，分子迁移率研究（高分子迁移率）的结果表明，玻璃态固体中的分子迁移率与其结晶趋势之间的关系似乎并不遵循预期模式，即不会像预期的那样通过对玻璃态、过冷液体和 CAR 的液态进行热处理而发生结晶。现代量热法和定量热分析为 CAR 的晶态和非晶态提供了基本的动力学和热力学信息。
