Ternary Phase Diagram for Salicylic Acid/Nicotinamide/Water System and Dissolution of Salicylic Acid/Nicotinamide Cocrystals in Water

Abstract

Cocrystals, which are crystallized intermolecular compounds composed of host and guest (organic) compounds, are receiving attention in order to improve the solubility of insoluble host organic compounds. In this study, the composition profiles of salicylic acid (SA) and nicotinamide (NA) in an aqueous solution were examined when SA/NA cocrystals were dissolved in water, and the dissolving phenomena of SA/NA cocrystals were investigated. SA/NA cocrystals were able to be produced by a rapid cooling method of an SA/NA ethanol (EtOH) solution, a rapid cooling method of melt for SA/NA mixtures, evaporation to dryness of an SA/NA EtOH solution and mechano-chemical processing by a planetary ball mill. A ternary phase diagram for the SA/NA/water (H₂O) system was made and it grouped near the NA composition axis and two eutectic points existed. Tablets composed of SA/NA cocrystals were dissolved in water and the changes in the composition ratios of SA to NA in the solution and the surface compositions on their tablets with experiment duration were examined. Changes in the composition ratios of SA to NA in a solution for case of SA/NA cocrystals were compared with those for equimolar mixtures of SA and NA crystals. SA and NA composition profiles in a solution and on tablet surfaces are shown and the dissolving phenomena of SA and NA cocrystals are discussed.