Determinação estrutural de sais de Mefloquina através da difração de raios x por monocristal

Abstract

Malaria is an infection that belongs to the group of neglected tropical diseases, rendering it less appealing for the pharmaceutical industry to develop new drugs for its treatment. Mefloquine (Mf) is an important antimalarial agent that belongs to Classes II or IV of the Biopharmaceutical Classification System. To identify a solid form of Mf, a crystal engineering approach can be employed. This work demonstrates the application of X-ray crystallography for the characterization of new solid forms of pharmaceutical compounds. The preparation of new Mf salts was performed in three steps: the obtaining of MF in its free base; reaction between Mf and hydrobromic (HBr) and oxalic (Oxa) acids, and crystallization. As a result of the crystallization process, the salts Mefloquine Hydrobromide (MfHBr) and Mefloquine Oxalate (MfOxa) were obtained. The crystals were characterized using single-crystal X-ray diffraction (SCXRD). Based on fundamental crystallographic concepts, the electron density function for the structure of the salts was constructed, from the SCRXD data. In the MfHBr structure, the molecules crystallize in the triclinic P¯1 space group, as a hydrate structure. MfOxa crystallizes in a monoclinic P21/n space group and as an ethanol solvate. To further characterize the Mf salts, thermal analysis measurements (DSC and TGA) were performed. The DSC/TGA analyses show that the MfHBr structure is stable between 25 and 214 ªC. MfOxa desolvates at approximately 120°C and degrades starting from 190°C. Although further testing is required for complete characterization, MfOxa and MfHBr represent promising candidates as new active pharmaceutical ingredient solids.