A Review on High Pressure Experiments for Study of Crystallographic Behavior and Polymorphism of Pharmaceutical Materials

Abstract

A review of work on pharmaceutical molecular materials studied under high pressure was carried out. The behavior of the crystallographic structure of these materials is observed under high pressure thanks to X-ray diffraction laboratory, synchrotron experiments or Raman spectroscopy. In particular, the highlighting of phase transitions and the discovery of new crystallographic forms are an important application of these methods. Works performed from the last two decades shows that two ways are mainly used: direct compression of powders or single crystals and crystallization under high pressure in different solvents. The evolution of the cell volumes and lattice parameters of different compounds have been observed with direct compression experiments of the order of few GPa to few tens of GPa. On few compounds the discovery of new polymorphic forms is highlighted. High pressure crystallization experiments generally require lower pressure ranges, on the order of few hundred to few GPa. For numerous pharmaceutical molecules, new polymorphs but also salts, solvates, hydrates or co-crystals can be obtained. It depends on the solvents and pressure ranges chosen. It shows the possibility to select the desired crystallographic form of a given active principle by a judicious choice of these parameters.

Keywords: Active pharmaceutics ingredients; High pressure; Polymorphism; Raman spectroscopy; X-ray diffraction.