Polymorphism in cocrystals of metronidazole benzoate

Abstract

In contrast to the widespread polymorphism of single component drugs, polymorphism in cocrystals is still uncommon and often poorly understood. While there are numerous reports of polymorphic forms of single component drugs, limited studies have been conducted on polymorphism in cocrystals, primarily examining structural relationships among the polymorphs. As the use of cocrystals in the pharmaceutical industry grows, understanding the impact of polymorphism on the properties of these compounds is crucial. This work reports two polymorphic cocrystals from the metronidazole benzoate using salicylic acid and fumaric acid as coformers. The crystal structures were successfully elucidated using single crystal X-ray diffraction. The structural analysis revealed differences in crystal packing and conformation, indicating that these polymorphs cannot be classified as a single class. In addition, thermal analysis and powder X-ray diffraction were performed to investigate the interconversion dynamics between the polymorphic forms of these cocrystals. The cocrystals based on salicylic acid showed slightly improved water solubility compared to the drug and the fumaric acid cocrystal, with similar solubility levels for both polymorphs of each cocrystal.