Crystal architecture and physicochemical properties of felodipine solvates

Abstract

Solvates of the calcium-channel blocking agent felodipine with three structurally related high-boiling point solvents, dimethylacetamide (DMAA), dimethylethyleneurea (DMEU) and tetramethylurea (TMU), are described. The solvates can be formed either by solution crystallisation or solvent-drop mechanical grinding. In all of the crystal structures, the solvent molecule accepts an N–H⋯O hydrogen bond from felodipine. Analysis of the conformational preferences of the felodipine molecule in the crystal structures shows that it adopts a higher-energy conformation in the solvate with TMU. Hot-stage microscopy shows that the solvates decompose below the boiling point of the solvent, then the solvent condenses and dissolves the desolvated felodipine. The decomposition temperature of the solvate is correlated with the van der Waals molecular volume for the solvent molecule within the crystal structure. Measurements of the aqueous dissolution rate show that the concentration of felodipine during the first hour is increased by 4–6 times for dissolution of the solvates compared to pure felodipine.