School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.
Int J Pharm. 2019 Jul 20;566:361-370. doi: 10.1016/j.ijpharm.2019.05.071. Epub 2019 May 29.
In this paper, two novel polymorphs of adefovir dipivoxil-saccharin (AD-SAC) cocrystals, forms II and III, were prepared and characterized by PXRD, DSC, FT-IR and SEM. Polymorphic transformations of these two forms and the known form (form I) were also investigated. In comparison to form I, forms II and III of AD-SAC cocrystals showed different thermal behaviors on DSC, characteristic diffraction peaks on PXRD and absorption spectra on FT-IR. In addition, form I exhibited an irregular plate-like shape, while forms II and III showed as needle-like shape and stubby columnar shape, respectively. During the heating process on DSC, forms I and II underwent solid-solid transformations to form III with endothermic transition peaks, suggesting that forms I and II were enantiotropically related to form III. Furthermore, slurry conversion experiments in ethanol showed forms II and III would quickly convert to form I by solution-mediated transformation, indicating that form I was the most stable form among three forms of AD-SAC cocrystal from 15 to 50 °C.
本文制备并表征了阿德福韦酯-糖精（AD-SAC）共晶的两种新的多晶型物 II 型和 III 型，分别通过 PXRD、DSC、FT-IR 和 SEM 进行了表征。还研究了这两种形式和已知形式（形式 I）的多晶型转变。与形式 I 相比，AD-SAC 共晶的形式 II 和 III 在 DSC 上表现出不同的热行为、PXRD 上的特征衍射峰和 FT-IR 上的吸收光谱。此外，形式 I 呈现出不规则的板状形状，而形式 II 和 III 分别呈现出针状和粗柱状形状。在 DSC 的加热过程中，形式 I 和 II 经历了固-固转变，形成了具有吸热转变峰的 III 型，表明形式 I 和 II 与形式 III 是对映相关的。此外，在乙醇中的浆液转化实验表明，形式 II 和 III 会通过溶液介导的转化迅速转化为形式 I，表明在 15 至 50°C 范围内，形式 I 是 AD-SAC 共晶三种形式中最稳定的形式。
