Polymorphic Drugs - Challenges and Characterisation of the Thermodynamic Instability in Pharmaceutical Formulation

Active Pharmaceutical Ingredients (API’s) can exist in an assortment of strong structures which includes polymorphs, pseudo polymorphs, salts, co-crystal and shapeless solids. A distinct solid form of drugs can exhibit different mechanical, thermal, physical, and chemical properties, which can ultimately alter the drug properties such as its hygroscopic nature and erratic bioavailability. Therefore, a change in the polymorphic form is regarded as one of the most challenging issues faced by the pharmaceutical industry during the formulation of a dosage form. However, this issue could be overcome by certain extent by obtaining a new polymorphic version of pharmaceuticals with a desirable physicochemical property, which would be expected to address the problem. The potential cost and time delay of altering crystal structures during late-stage drug development stimulates rigorous and early polymorphism characterization. Characterization of such thermodynamic instability in pharmaceutical formulation with polymorphic drugs and their polymorphic changes challenge the crystallographic, spectroscopic, and thermal techniques that are widely employed to identify, quantify, and characterise drug and formulations. However, polymorphism in API’s and their formulations is regulated by several regulatory authorities. This article focuses on the most essential polymorph modifications in formulation in terms of pharmaceutical safety and efficacy.