Ternary Phase Diagrams of Trospium Chloride Cocrystals

Abstract

Ternary phase diagrams are used for the cocrystal synthesis because they allow to conveniently choose the coformer and to define optimal process conditions. This article deals with the construction of predicted and experimental ternary phase diagrams of trospium chloride as the active substance. At first, the pre-selected co-crystals of trospium chloride with salicylic acid and trospium chloride with oxalic acid were prepared. Subsequently, the solubilities of the individual components and the co-crystals were measured. Values obtained were used for the prediction of cocrystals from ternary phase diagrams in two solvents (propan-1-ol and butan-1-ol). Experimental construction of diagrams was based on the detailed analysis of prepared suspensions of well-defined composition. Solid phases of suspensions were analyzed by X-ray powder diffraction, the liquid phases by UV-Vis spectrophotometry and gravimetry. In this way, diagrams for the co-crystal of trospium chloride with salicylic acid were created. Finally, predicted and experimental constructions were compared and the benefits and differences discussed.