In Situ Metastable Form: A Route for the Generation of Hydrate and Anhydrous Forms of Ceritinib

Abstract

Ceritinib is an anaplastic lymphoma kinase (ALK) inhibitor used for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC). This BCS class IV drug is developed by Novartis and traded under the name Zykadia. To date two forms [Form A (marketed form) and B] of ceritinib are disclosed in international patent application US 2013/0274279 A1. However, the crystal structure and insight into any solid form of this compound are not available in the literature. In order to achieve better physicochemical properties compared to known solid forms of this compound, novel polymorph identification is chosen as one of the challenging paths to address the issue. In our comprehensive polymorph screening, including in silico and experimental investigations, we discovered three novel solid forms of ceritinib. Out of these three solid forms, two are neat (Form 1 and Form 3) and the remaining one is a hydrate (Form 2). All synthesized forms are further characterized by powder X-ray diffraction, differential...