Polymorphism and structural studies of isoniazid derivatives

Abstract

Crystal polymorphism is the capacity of a solid crystalline form to exist in more than one structural arrangement. In the pharmaceutical setting investigations into the polymorphic forms of potential drugs are of vital importance since different crystalline forms can affect bioavailability, mechanical, thermal, and chemical properties. One such example is isonicotinic acid-(1-phenylethylidene) hydrazide (IPH), a derivative of the popular drug isoniazid (used as first line treatment against Mycobacterium tuberculosis) was found to crystallise in six different polymorphic forms. Each crystal structure was determined using X-ray diffraction techniques and including the thermal phase relationships of the polymorphic compound were delineated. In addition to polymorph elucidation, isonicotinic acid-(1-phenylethylidene) hydrazide was modified with –OH and –NH2 at various aromatic positions, creating geometric pyridyl isomers. In-depth studies of these pyridyl isomers revealed a diverse range of supramolecular aggregates. Preliminary thermal screening suggests that only a small selection of these pyridyl isomers present potential polymorphic activity for further study.