RESUMO
Over time platinum-based anticancer drugs have dominated the market, but their side effects significantly impact the quality of life of patients. Alternative treatments are being developed all over the world. The titanocene and auranofin families of compounds, discovered through an empirical search for other metal-based therapeutics, hold tremendous promise to improve the outcomes of cancer treatment. Herein we present a historical perspective of these compounds and review current efforts focused on the evolution of their ligands to improve their physiological solution stability, cancer selectivity, and antiproliferative performance, guided by a clear understanding of the coordination chemistry and aqueous speciation of the metal ions, of the cytotoxic mechanism of action of the compounds, and the external factors that limit their therapeutic potential. Newer members of these families of compounds and their combination in novel bimetallic complexes are the result of years of scientific research. We believe that this review can have a positive impact in the development and understanding of the metal-based drugs of gold, titanium, and beyond.
RESUMO
Solid dispersions embed active pharmaceutical ingredients in polymeric carriers to improve their solubility. Three solid dispersion preparation techniques are typically employed: solvent evaporation, solvent-fusion, and fusion methods. Although these are also widely recommended as preparative methods for phase diagram determination, few examples exist concerning their effect on the resulting polymorph, once the solid dispersion is produced. In this study, the influence of these methods on the polymorphic form obtained in crystalline solid dispersions (CSDs) composed of flufenamic acid (FFA) and poly(ethylene glycol) was investigated. The physical mixtures and CSDs were characterized by powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry. The results reveal that the fusion method leads to concomitant polymorphs (mainly FFA I and III) in the CSDs. In contrast, the solvent evaporation and solvent-fusion methods lead to FFA III. Collectively, these results demonstrate that preparative methods have a significant influence on the phase diagrams determined (average relative deviation ≤8%), which are often used to justify the design space of manufacturing processes, including those deemed "continuous." Consequently, choosing a preparation method that results in the desired polymorph is crucial to ensure accurate determination of phase diagrams and critical quality attributes of formulations.
