Department of Physical Chemistry, A.M. Butlerov Institute of Chemistry, Kazan Federal University, 420008, Kremlevskaya, 18, Kazan, Russia.
Department of Physical Chemistry, A.M. Butlerov Institute of Chemistry, Kazan Federal University, 420008, Kremlevskaya, 18, Kazan, Russia.
Int J Pharm. 2021 Apr 15;599:120427. doi: 10.1016/j.ijpharm.2021.120427. Epub 2021 Mar 2.
The use of the amorphous forms of drugs is a modern approach for the enhancement of bioavailability. At the same time, the high cooling rate needed to obtain the metastable amorphous state often prevents its investigation using conventional laboratory methods such as differential scanning calorimetry, X-ray powder diffractometry. One of the ways to overcome this problem may be the application of Fast Scanning Calorimetry. This method allows direct determination of the critical cooling rate of the melt and kinetic parameters of the crystallization for bad glass formers. In the present work, the amorphous states of dopamine hydrochloride and atenolol were created using Fast Scanning Calorimetry for the first time. Critical cooling rates and glass transition temperatures of these drugs were determined. Based on the values of the kinetic fragility parameter, dopamine hydrochloride glass can be considered strong, while atenolol glass is moderately strong. Both model-based and model-free approaches were employed to determine the kinetic parameters of cold crystallization of dopamine and atenolol. The results were compared with the data from isothermal crystallization experiments. The Nakamura crystallization model provides the best description of the crystallization process and can be used to predict the long term stability of the amorphous forms of the drugs. The presented approaches may find applications in predicting the storage time and choosing the optimal storage conditions of the amorphous drugs prone to crystallization.
药物无定形形式的使用是提高生物利用度的一种现代方法。同时，获得亚稳无定形状态所需的高冷却速率通常会阻止使用常规实验室方法（如差示扫描量热法、X 射线粉末衍射法）对其进行研究。克服这个问题的一种方法可能是应用快速扫描量热法。该方法允许直接确定熔体的临界冷却速率和不良玻璃形成物的结晶动力学参数。在本工作中，首次使用快速扫描量热法制备了盐酸多巴胺和阿替洛尔的无定形状态。确定了这些药物的临界冷却速率和玻璃化转变温度。基于动力学脆性参数的值，可以认为盐酸多巴胺玻璃是强玻璃，而阿替洛尔玻璃是中等强度的玻璃。采用基于模型和无模型的方法来确定多巴胺和阿替洛尔的冷结晶动力学参数。将结果与等温结晶实验数据进行了比较。Nakamura 结晶模型对结晶过程的描述最好，可以用于预测药物无定形形式的长期稳定性。所提出的方法可以用于预测易结晶的无定形药物的储存时间和选择最佳储存条件。
