Emphasis on pharmaceutically acceptable solvates: linking solubility with isostructurality for better drug design

Abstract

Acalabrutinib, an anti-cancer drug, was approved by the USFDA in 2017. However, the acalabrutinib capsules (marketed as CALQUENCE) posed certain challenges for cancer patients. To overcome these issues, the brand company developed acalabrutinib maleate tablets, which received USFDA approval in 2022. While acalabrutinib has multiple solid forms, acalabrutinib maleate salt exists only as a hydrate. This study addressed the literature discrepancy regarding acalabrutinib maleate whether it is a monohydrate or sesquihydrate. It also aimed to develop a novel solid form of acalabrutinib maleate salt with improved or comparable physicochemical properties to meet the unmet needs of cancer patients. This is the first study to report a new solid form, specifically a pharmaceutically acceptable solvate of acalabrutinib maleate, and to conduct its structural investigation. Various analytical tools, including X-ray diffraction (powder XRD and single crystal XRD), spectroscopy (¹H-NMR and HPLC), thermal analyses (DSC and TGA), and physicochemical characterization (solubility and stability), were used to investigate the properties of the new solid form. The physicochemical studies indicated that the new solid form of acalabrutinib maleate has similar solubility to its commercial form and remained stable after a six-month study under FDA-recommended storage conditions. To the best of our knowledge, this is the first time the reason for similar solubility has been linked to isostructurality, using Hirshfeld surface and Xpac analysis. Therefore, the novel, stable, and scalable new solid form discussed in this study is a potential candidate for early market launch due to its similar properties to the commercial form.