Theoretical construction of thermodynamic relations for a solvent-controlled phase transition to improve the bioavailability of drugs: a case study of indomethacin

Abstract

The thermodynamic aspects of the polymorphic phase transition from α-indomethacin to γ-indomethacin are the fundamental key to find the most bioavailable phase of indomethacin. In the present work, varying the solvent permittivity changes the polymorphic transitions. Hence, the thermodynamic properties such as enthalpy, Gibbs free energy, and entropy of both indomethacin polymorphs are determined in terms of the solvent permittivity at T0=298.15 K and P0=1 atm., which are crucially related to the stability, spontaneity, and reversibility of the polymorphic transformation.