In the introduction to this review the complex chemistry of solid-state pharmaceutical compounds is summarized. It is also explained why the density functional theory (DFT) periodic calculations became recently so popular in studying the solid APIs (active pharmaceutical ingredients). Further, the most popular programs enabling DFT periodic calculations are presented and compared. Subsequently, on the large number of examples, the applications of such calculations in pharmaceutical sciences are discussed. The mentioned topics include, among others, validation of the experimentally obtained crystal structures and crystal structure prediction, insight into crystallization and solvation processes, development of new polymorph synthesis ways, and formulation techniques as well as application of the periodic DFT calculations in the drug analysis.

This review discusses a set of instrumental and computational methods that are used to characterize hydrated forms of APIs (active pharmaceutical ingredients). The focus has been put on highlighting advantages as well as on presenting some limitations of the selected analytical approaches. This has been performed in order to facilitate the choice of an appropriate method depending on the type of the structural feature that is to be analyzed, that is, degree of hydration, crystal structure and dynamics, and (de)hydration kinetics. The presented techniques include X-ray diffraction (single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD)), spectroscopic (solid state nuclear magnetic resonance spectroscopy (ssNMR), Fourier-transformed infrared spectroscopy (FT-IR), Raman spectroscopy), thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)), gravimetric (dynamic vapour sorption (DVS)), and computational (molecular mechanics (MM), Quantum Mechanics (QM), molecular dynamics (MD)) methods. Further, the successful applications of the presented methods in the studies of hydrated APIs as well as studies on the excipients’ influence on these processes have been described in many examples.

This review focuses on a combination of ab initio molecular dynamics (aiMD) and NMR parameters calculations using quantum mechanical methods. The advantages of such an approach in comparison to the commonly applied computations for the structures optimized at 0 K are presented. This article was designed as a convenient overview of the applied parameters such as the aiMD type, DFT functional, time step, or total simulation time, as well as examples of previously studied systems. From the analysis of the published works describing the applications of such combinations, it was concluded that including fast, small-amplitude motions through aiMD has a noticeable effect on the accuracy of NMR parameters calculations.