Exploration of Solid Forms of Crisaborole: Crystal Engineering Identifies Polymorphism in Commercial Sources and Facilitates Cocrystal Formation

Abstract

We report the discovery of three polymorphs of the very recently FDA-approved boron-containing active pharmaceutical ingredient, Crisaborole. Crisaborole displays polymorphism based on the syn (Form I) and anti (Form II) conformations of the hydroxyl group of the oxaborole ring as shown by single-crystal X-ray analysis. Forms I and II were discovered based on the availability from two different commercial suppliers, while Form III was obtained upon heating of Form I or II. A cocrystal based on 4,4′-bipyridine was also obtained.