Two New Polymorphic Cocrystals of Zafirlukast: Preparation, Crystal Structure, and Stability Relations

Two
new cocrystals of zafirlukast with piperazine, existing in
five different solid forms, have been discovered during a cocrystal
screening. The crystal structure of one of these forms has been determined
by single crystal X-ray diffraction, and the stability landscape of
the crystalline forms of the new cocrystal has been studied. In the
present article, we extend the knowledge about the solid state of
this important pharmaceutical drug for the treatment of asthma by
reporting the crystal structures of two new solvates (acetonitrile
and butanol) and the elusive anhydrous Form X, which have been solved
by single crystal X-ray diffraction.

本研究在共晶体（cocrystal）筛选过程中，发现了两种新型的扎鲁司特（zafirlukast）与哌嗪（piperazine）共晶体，该类共晶体存在五种不同的固体晶型。其中一种晶型的晶体结构已通过单晶X射线衍射（single crystal X-ray diffraction）解析，且本研究已对该新型共晶体的各类晶型的稳定性景观（stability landscape）展开研究。本文通过报道两种新型溶剂化物（solvate，分别为乙腈溶剂化物与丁醇溶剂化物）以及难以获取的无水晶型X的晶体结构，拓展了人们对这款重要哮喘治疗药物固态性质的认知，上述晶体结构均通过单晶X射线衍射完成解析。