�Thermal� evolution of structural, electronic and mechanical properties of different crystalline polymorphs of three active pharmaceutical ingredients (API) are reported by adopting the B3LYP hybrid density functional corrected with a semi-empirical contribution that takes into account the damped 1/r6 term added a posteriori as originally proposed by Grimme. Results show that the adopted approach is reliable enough to reproduce thermal effects on lattice energies and other measurable physico-chemical quantities which are directly related to the nature of inter- and intra-molecular forces. It is found that the polymorphism of these materials can manifest into extremely different mechanical and energetic properties under different thermodynamic conditions. As a proof of principles, it is shown how the robustness of the adopted method can be successful in predicting experimentally unavailable physico-chemical quantities of other molecular crystals. Furthermore, possibilities of extending this computational approach to study surface properties of APIs and other molecular crystals will be discussed with the aim to elucidate the nature of the interaction of these materials with binders and atmospheric gas molecules such as water, oxygen etc. Such investigation can enable to reveal the nature of APIs in respect to a real world scenario to provide deeper insights including, but not limited to, the improvement of tableting industrial procedure and longevity of the materials with direct consequences on their in vivo absorption potential.

Mimicking thermal effects on bulk properties of molecular crystal polymorphs and cleaving their surfaces from first principles

247th National Meeting (2014)

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