Co-crystal engineering of phthalic acid derivatives with nitrogen-containing heterocyclic active pharmaceutical ingredients

Abstract

Fifteen heterocyclic active pharmaceutical ingredients were co-crystallized with phthalic acid derivatives, resulting in three series of co-crystals. Niacinamide, modified isoniazid (isoniazid modified with benzaldehyde), isoniazid, isonicotinamide niazid and benzhydrazide were co-crystallized with isophthalic acid, phthalic acid, terephthalic acid, 3-nitrophthalic acid, 5-aminoisophthalic acid, 5-nitroisophthalic acid, nitroterephthalic acid and diphenic acid. The three resulting series consisted of niacinamide, modified isoniazid and other N-heterocyclic API’s, each being co-crystallized with phthalic acid derivative co-formers. One of the phthalic acid derivatives – nitroterephthalic acid – was crystallized and the structure was published. The crystals formed were characterized by single crystal X-ray diffraction and their structures solved using Shelx. The structures were investigated, and their hydrogen bonding patterns as well as abnormalities were examined and discussed.