Determinação estrutural e caracterização de sais de Ciprofloxacino através da difração de raios-x por monocristal.

Abstract

Two of the most relevant properties for the production and formulation of new active pharmaceutical ingredients (APIs) are stability and solubility, which impact the efficacy of the expected therapeutic effect. However, these physicochemical properties are intrinsically related to the crystalline arrangement of the material. At this point, Crystal Engineering develops and designs new multicomponent crystals (MCs), optimizing the physicochemical properties of APIs. Ciprofloxacin (CIP) is an antibiotic of the fluoroquinolone class, mainly used for urinary tract infections. This API is present in class IV of the Biopharmaceutical Classification System, exhibiting low solubility and low permeability. The present work aims to demonstrate the application of crystallography for the analysis of pharmaceutical solids. CIP salts were designed based on the basicity of CIP, thus selecting mandelic and nitric acids as conformers. The characterizations of the obtained products were performed by single crystal X-ray diffraction (XRD), thermal analysis and solubility. Salts of Ciprofloxacin Nitrate (CIPNO3) and Ciprofloxacin Mandelate (CIP DL-Mand) were obtained. The CIPNO3 salt crystallizes in the triclinic space group, P\overline{1}. The Cip-DL-Mand salt crystallizes in the Monoclinic space group, P2_{1\}c. The crystal packing of CIPNO3 is characterized by the lack of hydrophilic channels, making it difficult to break chemical bonds by solvents. The Cip-DL-Mand salt also presents a dense crystal packing, but with the presence of water. This characteristic justifies the aqueous solubility of the CIPNO3 salt being lower than that of CIP DL-Mand, however, the solubility of both salts is higher than that of the pure API. These new phases have been shown to optimize the pharmacokinetic properties of the API and are candidates for CIP drugs. The results of this work bring important scientific contributions to the diversity of solid forms and define new solid formulations for use as antibiotics.