Salt or cocrystal of salt? Probing the nature of multicomponent crystal forms with infrared spectroscopy

Abstract

The recognition of the nature of a multicomponent crystal form (solvate, salt, cocrystal or cocrystal of salt) is of great importance for pharmaceutical industry because it is directly related to the performance of a pharmaceutical ingredient, since there is interdependence between the structure, its energy and its physical properties. In this context, here we have identified the nature of multicomponent crystal forms of the anti-HIV drug lamivudine with mandelic acid through infrared spectroscopy. These investigated crystal forms were the known S-mandelic acid cocrystal of lamivudine R-mandelate trihydrate (1), a cocrystal of salt, and lamivudine R-mandelate (2), a salt. This approach also supports the identification and distinction of both ionized and unionized forms of mandelic acid in the infrared spectrum of 1. In this way, infrared spectroscopy can be useful to distinguish a cocrystal of salt from either salt or cocrystal forms. In the course of this study, for the first time we have also characterized and determined the crystal structure of R-mandelic acid cocrystal of sodium R-mandelate (3).