New forms of apremilast with halogen derivatives of benzoic acid

Abstract

Apremilast is a poorly soluble active pharmaceutical ingredient. It is prone to form multicomponent crystals and crystallizes in very similar molecular arrangements. We have crystallized apremilast with derivatives of halogen benzoic acid. Such compounds are known to moderate crystallization processes to different polymorphs of paracetamol. Surprisingly, apremilast structure packing was able to accommodate the o- and m-halogen benzoic acid derivatives in the same structure type as for known structures. On the other hand, crystallization with p-halogen benzoic acid derivatives leads to a cocrystal form with a rare molecular arrangement, which is likely less stable, and hence not preferred in the structures with smaller co-formers. The new forms were characterized by Single Crystal and Powder X-Ray Diffraction, and their stability was studied and compared by Differential Scanning Calorimetry and Thermogravimetric Analysis.