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

TL;DR

This paper develops a theoretical framework to understand how solvent and temperature influence the thermodynamic stability of indomethacin polymorphs, aiming to optimize drug bioavailability.

Contribution

It introduces a thermodynamic model linking solvent permittivity and temperature to polymorphic phase stability, enhancing control over drug bioavailability.

Findings

Thermodynamic properties vary with solvent permittivity and temperature.

Polymorphic transition stability depends on solvent conditions.

Model aids in selecting optimal conditions for drug formulation.

Abstract

The thermodynamic aspects of the polymorphic phase transition from {\alpha}-indomethacin to {\gamma}-indomethacin are the fundamental key to find the most bioavailable phase of indomethacin. In the present work, varying the temperature and 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 as functions of indomethacin's temperature in a vacuum, which are crucially related to the stability, spontaneity, and reversibility of the polymorphic transformation.