Theoretical derivation and practical application of energy temperature diagrams as an instrument in preformulation studies of polymorphic drug substances

The construction of semiquantitative energy/temperature (E/T) diagrams is discussed on the basis of thermodynamic equations. An E/T diagram describes the temperature dependence of the enthalpy and the Gibbs free energy of polymorphs. Knowledge of the E/T diagram of a compound permits the prediction of relative physicochemical values for polymorphs. Construction and interpretation of E/T diagrams is discussed with reference to the drug substances nimodipine and acemetacin. The predicted data are compared with experimental values.