a Laboratory of Pharmaceutics, School of Pharmacy , Nihon University , Chiba , Japan.
b Faculty of Pharmaceutical Sciences , Tokushima Bunri University, Kagawa Campus , Kagawa , Japan.
Drug Dev Ind Pharm. 2018 Apr;44(4):582-589. doi: 10.1080/03639045.2017.1405433. Epub 2017 Nov 29.
The aim of this study is to evaluate the relative stability of pharmaceutical cocrystals consisting of paracetamol (APAP) and oxalic acid (OXA) or maleic acid (MLA).
These observations of cocrystal stability under various conditions are useful coformer criteria when cocrystals are selected as the active pharmaceutical ingredient in drug development.
The relative stability was determined from the preferentially formed cocrystals under various conditions.
Cocrystal of APAP-OXA was more stable than that of APAP-MLA in a ternary cogrinding system and possessed thermodynamical stability. On the other hand, when grinding with moisture or maintaining at high temperatures and relative humidity conditions, APAP-MLA was more stable, and OXA converted to OXA dihydrate. In the slurry method, APAP-OXA was more stable in aprotic solvents because the APAP-OXA with low-solubility product precipitated.
The relative stability order was affected by preparing conditions of presence of moisture. This order might attribute to the small difference of crystal structure in the extension of the hydrogen bond network.
本研究旨在评估对乙酰氨基酚（APAP）和草酸（OXA）或马来酸（MLA）组成的药物共晶的相对稳定性。
这些在各种条件下共晶稳定性的观察结果对于共晶作为药物开发中的活性药物成分的选择是有用的共晶形成剂标准。
通过在各种条件下优先形成的共晶来确定相对稳定性。
在三元共研磨体系中，APAP-OXA 共晶比 APAP-MLA 共晶更稳定，具有热力学稳定性。另一方面，在研磨时存在水分或在高温和高湿度条件下保持时，APAP-MLA 更稳定，并且 OXA 转化为 OXA 二水合物。在浆状方法中，由于低溶解度产物沉淀，APAP-OXA 在非质子溶剂中更稳定。
相对稳定性顺序受存在水分的制备条件的影响。这种顺序可能归因于氢键网络扩展中晶体结构的微小差异。
