Polymorphism refers to different structural forms of a chemical substance and is associated with the ability of a solid material to exist in two or more crystal structures. In these structures is possible to observe different arrangements or conformations of the molecules. Interestingly, more than 50% of active pharmaceutical ingredients are estimated to have more than one polymorphic form; however, some of the polymorphs, eventually, can not have pharmaceutical function. As a consequence, it is important to investigate several polymorphic forms and to try understand their conformations and possible influence in their biochemical activities.

Haloperidol (C21H23ClFNO2) is a drug used in the treatment of several diseases including schizophrenia, bipolar disorder, and some psychosis, among others. Theoretically, one expects the occurrence of at least two conformers fo haloperidol, a trans and a gauche conformation as calculated by the 4-21G level some years ago. Haloperidol crystallizes in a monoclinic structure with four molecules per unit cell.

Raman spectroscopic study with the crystal submitted to high pressure showed haloperidol undergoes two phase transitions, at 2 GPa and 4.2 GPa. The first phase transition is accompanied by changes in the dw/dP curves of low-wavenumber region of the spectrum and by change of number of modes, suggesting the material change crystal structure. In the second phase transition the main modifications are only change in the dw/dP curves associated with particular internal modes, indicating that the crystal is changing conformation without modification of the symmetry of the unit cell.