Department of Experimental and Clinical Pharmacology, Medical College of Rzeszow University, The University of Rzeszow, 35-310, Rzeszow, Poland.
Department of Experimental and Clinical Pharmacology, Medical College of Rzeszow University, The University of Rzeszow, 35-310, Rzeszow, Poland; National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.
Eur J Pharm Sci. 2023 Apr 1;183:106397. doi: 10.1016/j.ejps.2023.106397. Epub 2023 Feb 1.
The characterization of cytisine (CYT) and its blends with poly(lactic acid) was performed using thermal analysis, elemental analysis, infrared spectroscopy, and powder X-ray diffractometry. The heat capacities, total enthalpy, and phase transitions of CYT were established from 1.8 to 448.15 K (-271.35 - 175 °C) by advanced thermal analysis. Data were obtained using a Quantum Design Physical Property Measurement System (PPMS) and a differential scanning calorimetry (DSC). The low-temperature heat capacity of the crystalline CYT in the range of 1.8 to 300 K (-271.35 - 26.86 °C) was measured by PPMS and fitted to a theoretical model in the low temperature region below 11 K (-262.15 °C), to orthogonal polynomials in the middle range 5 K < T < 60 K (-268.15 °C < t < -213.15 °C) and to the Debye and Einstein functions in the high range of temperature above 60 K (-213.15 °C). The liquid heat capacity was calculated based on the approximated linear regression data above the molten state of the experimental heat capacity of CYT obtained by the standard DSC measurements, and it was expressed as C = 0.0838T + 346.78 J·K·mol. The calculated heat capacity in the solid state was extended to a higher temperature and was used, together with liquid heat capacity, as the reference baselines for the advanced thermal analysis of CYT. The PPMS and DSC/TMDSC methods are complementary methods for thermal analysis of cytisine. The PPMS method allowed determination of the equilibrium heat capacity in the solid state, which together with the equilibrium heat capacity in the liquid state allowed to analyze of the experimental apparent heat capacity of cytisine obtained based on DSC. The melting temperature and the total heat of fusion of crystalline material were established as 431.8 K (158.65 °C) and 26.5 kJ·mol, respectively. The solid and liquid heat capacities and transition parameters of CYT were applied to calculate total enthalpies for fully amorphous and crystalline states. Analyses of DSC and X-ray confirmed the presence of the solid-solid transition linking with not so far described a polymorphism phenomenon of CYT. Based on the thermogravimetric analysis the temperature of degradation of CYT was determined as 460.5 K (187.35 °C). Also, a preliminary thermal analysis of the blends of cytisine and poly(lactic acid) as a new candidate for drug delivery system was presented.
采用热分析、元素分析、红外光谱和粉末 X 射线衍射法对烟碱（CYT）及其与聚乳酸（PLA）共混物进行了表征。使用先进的热分析技术，在 1.8 至 448.15 K（-271.35 至 175°C）范围内确定了 CYT 的热容、总焓和相变。数据是使用 Quantum Design 物理性质测量系统（PPMS）和差示扫描量热法（DSC）获得的。使用 PPMS 测量了在 1.8 至 300 K（-271.35 至 26.86°C）范围内结晶 CYT 的低温热容，并将其拟合到低温区域（低于 11 K（-262.15°C））的理论模型，5 K < T < 60 K（-268.15°C < t < -213.15°C）的正交多项式和高于 60 K（-213.15°C）的温度的德拜和爱因斯坦函数。根据通过标准 DSC 测量获得的 CYT 实验热容的熔融状态以上的近似线性回归数据计算了液体热容，并表示为 C = 0.0838T + 346.78 J·K·mol。将固态热容扩展到更高的温度，并与液态热容一起，作为 CYT 高级热分析的参考基准。PPMS 和 DSC/TMDSC 方法是烟碱热分析的互补方法。PPMS 方法允许确定固态平衡热容，与液态平衡热容一起，用于分析基于 DSC 获得的结晶烟碱的实验表观热容。结晶材料的熔点和总熔融热分别确定为 431.8 K（158.65°C）和 26.5 kJ·mol。CYT 的固态和液态热容以及相变参数用于计算完全非晶态和晶态的总焓。DSC 和 X 射线分析证实存在与迄今未描述的 CYT 多晶现象相关的固态-固态转变。根据热重分析，确定 CYT 的降解温度为 460.5 K（187.35°C）。此外，还提出了烟碱和聚乳酸（PLA）共混物作为药物输送系统新候选物的初步热分析。
