Unexpected Single Crystal Growth Induced by a Wire and New Crystalline Structures of Lapatinib

Abstract

Single crystal growth of lapatinib free base was induced by immersion of a copper wire into a supersaturated methanolic aqueous solution yielding monoclinic anhydrous plates (space group P21/c, Form 1) and needles of a previously unknown channel hydrate (in P42212). Also, a new method has been developed herein to obtain anhydrous Form 1 via acid–base reaction of lapatinib ditosylate and sodium methoxide, avoiding the usage of an aqueous solution and hydrate formation. Anhydrous Form 2 as well as new solvates were produced via solution mediated transformation experiments, including a dichloromethane solvate with a powder X-ray diffraction pattern similar to that of anhydrous Form 2. Differential scanning calorimetry and solution equilibrium experiments helped to elucidate the interconversion pathways between Form 1, Form 2, and the solvates.