Improving mechanical properties of desloratadine via multicomponent crystal formation
Improving mechanical properties of desloratadine via multicomponent crystal formation
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DOI：
10.1016/j.ejps.2017.09.035
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发表时间：
2018-01-01
影响因子：
4.6
通讯作者：
Yonemochi, Etsuo
中科院分区：
文献类型：
--
作者：
Ainurofiq, Ahmad;Mauludin, Rachmat;Yonemochi, Etsuo
我们报告了第一个地洛他定（一种重要的抗组胺药物）与药学上可接受的苯甲酸共形成物的多组分晶体。单晶结构分析表明，由于质子从苯甲酸转移到地氯雷他定分子，这种新型多组分晶体被归类为作为盐。通过形成盐多元晶体，我们证明了多元晶体的可压片性和可塑性比母体药物有所改善。此外，地氯他定-苯甲酸多组分晶体中既没有观察到封端也没有观察到层压趋势。层状结构和滑移面的存在被认为与这种改进有关。在这种情况下，地氯雷他定-苯甲酸盐显示出在水和HCl 0.1N介质中改善的溶解度和在水中更好的溶出曲线。然而，在0.1N盐酸介质中的溶解速率被发现基本上是无关紧要的。
We report the first multicomponent crystal of desloratadine, an important anti-histamine drug, with a pharmaceutically acceptable coformer of benzoic acid. The single crystal structure analysis revealed that this novel multicomponent crystal is categorized as salt due to the proton transfer from benzoic acid to the desloratadine molecule. By forming the salt multicomponent crystal, we demonstrated that the tabletability and plasticity of the multicomponent crystal was improved from the parent drug. In addition, neither capping nor lamination tendency was observed in the desloratadine-benzoic acid multicomponent crystal. The existence of a layered structure and slip planes are proposed to be associated with this improvement. The desloratadine-benzoate in this case shows an improved solubility in water and HCl 0.1N media and a better dissolution profile in water. However, the dissolution rate in HCl 0.1N media was found to be essentially indifference.