Molecular Basis of Water Sorption Behavior of Rivaroxaban-Malonic Acid Cocrystal

The present study aims to investigate the molecular basis of water sorption behavior of rivaroxaban-malonic acid cocrystal (RIV-MAL). It was hypothesized, that the amount of water sorbed by a crystalline solid is governed by the surface molecular environment of different crystal facets and their relative abundance to crystal surface. Water sorption behavior was measured using a dynamic vapor sorption analyzer. The surface molecular environment of different crystal facets and their relative contribution were determined using single crystal structure evaluation and face indexation analysis, respectively. The surface area-normalized water sorption for rivaroxaban (RIV), malonic acid (MAL), and RIV-MAL at 90% RH/25 °C was 0.28, 92.6, and 11.1% w/w, respectively. The crystal surface of MAL had a larger contribution (58.7%) of hydrophilic (Hphi) functional groups and showed the "highest" water sorption (92.6% w/w). On the contrary, RIV had a larger surface contribution (65.2%) of hydrophobic (Hpho) functional groups, and the smaller contribution (34.8%) of Hphi+Hpho groups exhibited the "lowest" water sorption (0.28% w/w). The "intermediate" water sorption (11.1% w/w) by RIV-MAL, as compared to RIV, was ascribed to the increased surface contribution of Hphi+Hpho groups (from 34.8 to 42.1%) and reduced hydrophobic surface contribution (from 65.2 to 57.9%). However, the significantly higher water gained (∼39-fold) by the cocrystal as compared to RIV, despite the nominal change in the surface contributions, was further attributed to the relatively stronger hydrogen bonding interactions between the surface-exposed carboxyl groups and water molecules. The study highlights that the amount of water sorbed by the cocrystal is governed by the surface molecular environment and additionally by the strength of hydrogen bonding. This investigation has implications on designing materials with a desired moisture-sorption property.