Introduction of Plasticity to Change Mechanical Behaviour of Pharmaceutical Crystals by Co-Crystallization: A Solution of Long Standing Problem in Isoniazid

Partha Pratim Bag*Email

Department of Chemistry, SRM University Sikkim, Gangtok, Sikkim 737102, India.

Abstract

Three co-crystals of the anti-tuberculosis drug Isoniazid (INH) with three analogous aromatic carboxylic acid namely phathalic acid (PA), isophathalic acid (IPA) and trimesic acid (TMA), were rationally designed and synthesized by slow evaporation method. Qualitatively, two-dimensional (2D) structure shows shearing behaviour on application of a mechanical stress, whereas the interlocked crystals are associated with brittleness in nature. Interestingly, co-crystallization of INH with PA converts its brittle nature of single crystal to shearing (plasticity) crystal i.e., 3D interlocked packing to 2D layer structure in INH/PA. Whereas, the co-crystals of INH/IPA and INH/TMA show brittle (non-plasticity) nature by keeping same 3D interlocked crystal packing as of INH. Improving the mechanical behaviour of single crystal of INH enhance its pharmaceutical acceptability and crystalline stability.

Introduction of Plasticity to Change Mechanical Behaviour of Pharmaceutical Crystals by Co-Crystallization: A Solution of Long Standing Problem in Isoniazid