Experimental Charge Density Analysis of the Anti-inflammatory Drug Meloxicam [sodium 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide Monohydrate]

Abstract

The charge density analysis of meloxicam sodium monohydrate [sodium 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide monohydrate] was performed with high-resolution X-ray diffraction data measured at low temperature (90 K). The experimental results were compared with those derived from the corresponding periodic theoretical calculations at the B3LYP/6-31G** level of theory. The multipolar charge-density analysis highlights the regions of meloxicam which are the most electronegative. These regions correspond to those forming short electrostatic interactions with the Na + cation. The molecular conformation in the crystal is maintained by a strong intramolecular N−H … O=C hydrogen bond. The Na + cation interacts with as much as five neighboring oxygen atoms. The strong hydrogen bonds N/O−H … O/N, the Na … O short contacts and hydrophobic aromatic stacking between the two aromatic cycles constitute the most represented and enriched contact types and act as the driving force in the crystal packing formation. The crystal packing presents several meloxicam anion dimers but also one Na+ … Na+ repulsive interactions which are largely compensated by the electrostatic favorable attractions between anions and cations.

Understanding Hygroscopicity of Theophyllineviaa Novel Cocrystal Polymorph: A Charge Density Study

“…Common themes across recent cocrystal studies have investigated the physical property enhancement of cocrystallization but the chemical explanation for the property alteration has largely not been identified. Charge density studies may provide the necessary tools to highlight weak interaction patterns across organic structures; − future coformer selection requires a strong understanding of how the physical properties are influenced by these interactions. ,, …”