The Challenge for Engineering Pharmaceutical Crystalline Solids: Scientific and Regulatory Affairs Perspectives for Crystal Structure Design and Prediction

Abstract

The Breakthrough into solid-state research has become emerging approach for structure determination of Active Pharmaceutical Ingredients (APIs) and excipeents that consequently influence their physic-chemical properties, biopharmaceutical and pharmacokinetic profiles. The concept of conventional pharmaceutical salts has been extended to multicomponent crystals which diversity in nature of the non-covalent intermolecular interactions determine the crystal packing patterns within the structures, and thus modulate the native properties of APIs. Therefore, the aim of this review is to highlight how accomplishments in crystallographic research on molecular crystal have influenced their classification and how these new solid phases have been recognized by the regulatory bodies. The advantage to explore the pharmaceutical crystalline solids of one API implies the selection of the form with favorable properties for the development of formulations for pharmaceutical dosage forms.