Polimorfismo em cocristais de benzoilmetronidazol

Abstract

Benzoylmetronidazole (BZMD) is an ester derived from metronidazole with antibacterial and antiprotozoal properties, being effective in the treatment of trichomoniasis, balantidiasis, ulcerative gingivitis and some anaerobic bacteria. It belongs to Class IV of the Biopharmaceutical Classification System (BCS), due to its low solubility and permeability. Cocrystals are a feasible alternative particularly for poorly water-soluble drugs that belong to the classes II and IV of BCS, since they offer the opportunity to modulate physicochemical properties, positively modifying biological properties related to these drugs. It is known that crystalline solids can exist in multiple forms, such as polymorphs. Cocrystals, as multicomponent solids, can exhibit this phenomenon, originating polymorphs of cocrystals, which may exhibit different physicochemical properties. This work aimed to produce cocrystals from BZMD using slow evaporation methodology and characterized them by structural, vibrational and thermal techniques. Two polymorphs with two polymorphic forms each were obtained from the BZMD and the coformers salicylic acid (SLC) and fumaric acid (FMA). The structures were successfully elucidated using single-crystal X-ray diffraction (SCXRD). In addition, X-ray powder diffraction (XRPD), optical microscopy (OM), infrared spectroscopy (IR) and thermal analysis were performed in order to obtain maximum information about the structures and to understand the dynamics of interconversion between the polymorphic forms of the cocrystals. The BZMDSLC cocrystals presented synthon, conformational and packing polymorphism, enantiotropically related. On the other hand, the BZMDFMA cocrystals were classified as synthon and conformational polymorphs. The methodology used proved to be efficient in the obtainment of BZMD cocrystals. The structural differences and the thermodynamic behavior of the new structures were investigated with the aid of the analytical techniques used. The obtaining of new solid forms from drugs, as well as their elucidation and characterization is the initial step to obtain new drugs.