Preparation and thermodynamic properties of Felodipine form IV

Form IV of the calcium channel blocker, Felodipine was obtained consistently via solvent evaporation in a pH-controlled solution, and followed by large-scale crystallization through seeding the saturated solution of Felodipine. Comparing with form I, the crystal form used in the marketed products, form IV has higher melting temperature but lower melting enthalpy. Hence, according to the heat of fusion rule, polymorphs I and IV should be in an enantiotropic relationship. Form I is thermodynamically more stable than form IV at room temperature. Their theoretical polymorphic transformation temperature was estimated at 87.6 A degrees C, which was also confirmed by the solvent-mediated polymorphic transformation experiments