Polymorphism of Nicotinamide Riboside Chloride and Crystal Structure Determination of the Most Stable Crystalline Form

Abstract

Three crystalline forms of nicotinamide riboside chloride (NR-Cl), namely Form A, Form B and Form C, were prepared and characterized. Form A and Form B are true polymorphs of anhydrous forms, while Form C is a pseudo-polymorph of a methanolate solvate form. The relative polymorphic stability relationship among these three crystalline forms was established, and Form B was found to be the most stable form with a higher crystal density (1.591 Mg/m3) and a higher melting/decomposing temperature (123 °C) compared to that of Form A (1.512 Mg/m3 and 119 °C). The crystal structure of Form B (orthorhombic P212121 space group, a = 7.0008(11) Å, b = 9.6465(15) Å, c = 17.971(3) Å, V = 1213.7(3) Å3, Z = 4) was determined by single crystal X-ray diffraction analysis.