Department of Pharmacy, University of Parma, Viale G.P. Usberti 27/A, 43124 Parma, Italy.
J Pharm Sci. 2010 Sep;99(9):3731-42. doi: 10.1002/jps.22072.
In the present study we report the solid-state properties of albendazole (ABZ) re-crystallized from different solvents for comparison with the commercially available form. Crystalline phases were characterized as to thermal behavior, X-ray diffractometry, both on powder and single crystal, and solubility in methanol or 0.1 N HCl. The relevant thermodynamic parameters were calculated from solubility measurements at different temperatures. The re-crystallization of ABZ both from methanol and N,N-dimethylformamide afforded a new stable polymorph form (Form II) enantiotropically related to the commercially available ABZ (Form I), the latter being the metastable form at ambient temperature. Both forms proved to be physically quite stable, likely due to a high-energy barrier for the activation of the interconversion. ABZ in the solid state represents a rather complex system in which the molecular structural differences that could be associated with the polymorphism are of at least four possible types, or combinations of these: (a) tautomeric; (b) different conformations of either or both of the side-chains attached to the bicyclic ring system; (c) the occurrence of molecular disorder or its absence; (d) no essential difference in molecular structure but different hydrogen bonding arrangements in the two polymorphs.
在本研究中，我们报告了从不同溶剂中重结晶的阿苯达唑（ABZ）的固态性质，以便与市售形式进行比较。对晶体相进行了热行为和 X 射线粉末衍射和单晶衍射的特征分析，并研究了在甲醇或 0.1N HCl 中的溶解度。通过在不同温度下的溶解度测量计算了相关的热力学参数。ABZ 从甲醇和 N，N-二甲基甲酰胺重结晶都得到了一种新的稳定多晶型形式（形式 II），与市售 ABZ（形式 I）呈反变相平衡，后者在环境温度下是亚稳形式。两种形式都被证明具有相当的物理稳定性，这可能是由于分子相互转化的活化能较高。ABZ 在固态中是一个相当复杂的系统，其中与多晶型有关的分子结构差异至少有四种可能类型，或这些类型的组合：（a）互变异构；（b）连接到双环系统的侧链的不同构象；（c）分子无序的发生或不存在；（d）分子结构没有本质区别，但两种多晶型体中氢键排列不同。
