Thermal Expansion of Carbamazepine: Systematic Crystallographic Measurements Challenge Quantum Chemical Calculations

We
report systematic temperature-dependent X-ray measurements on
the most stable carbamazepine polymorph. This active pharmaceutical
ingredient is used to demonstrate how the thermal expansion can probe
certain intermolecular interactions resulting in anisotropic expansion
behavior. We show that most structural features can be captured by
electronic structure calculations at the quasi-harmonic approximation
(QHA) provided a dispersion-corrected density functional based method
is employed. The impact of thermal expansion on the phonon modes and
hence free energy contributions is large enough to impact the relative
stability of different polymorphs.