Exploring Solid Form Landscape of Anticancer Drug Dimethylaminomicheliolide Fumarate: Crystal Structures Analysis, Phase Transformation Behavior, and Physicochemical Properties Characterization

Brain tumors are still the deadliest among all types of cancer even after decades of extensive research. Glioblastoma is the most common and aggressive form of primary malignant brain tumors. As an efficient NF-kappa B inhibitor, dimethylaminomicheliolide fumarate has shown excellent therapeutic effect for glioblastoma in clinical trials. To date, no reports about the solid forms of dimethylaminomicheliolide fumarate have been disclosed. Dimethylaminomicheliolide fumarate was thus an interesting subject for polymorphism exploration. In this work, four solid forms (Forms B, C, D, and E) were successfully obtained. The crystal structures exhibit similarity in molecular conformation and packing arrangements between Form C and Form E. The PXRD patterns and phase transition behavior suggest that Form B and Form D are likely to have similarities. Hirshfeld surfaces were generated for a better understanding of the relationships of different crystal forms. They were also characterized and evaluated by thermal analysis, polarizing microscope, and dynamic vapor sorption as well as powder properties tests. The comprehensive exploration of the solid form landscape provided essential knowledge for product development and quality control of this potential drug.

Automated summary

The study successfully obtained four solid forms of dimethylaminomicheliolide fumarate, with molecular conformation and packing arrangements showing similarity between Forms C and E, while Forms B and D may also have similarities. Comprehensive exploration through various testing methods provided essential knowledge for product development and quality control of the potential drug.