Compatibilidade farmacêutica e caracterização do estado sólido de dexametasona

Abstract

Dexamethasone is a synthetic glucocorticoid drug widely used in the treatment of acute and chronic inflammatory conditions, autoimmune diseases, some cancers, and several other pathologies. It is widely marketed worldwide, especially in solid dosage forms. There is little information in the literature about its solid state properties, including crystal lattice and polymorphism occurrence. In addition, there are no studies about the influence of pharmaceutical excipients on its physicochemical properties. Thus, this study aimed to evaluate dexamethasone compatibility with excipients commonly used in solid dosage forms and to investigate the occurrence of polymorphic forms. Compatibility study was conducted from the preparation of binary mixtures (1: 1; m / m) of dexamethasone with 12 excipients. Binary mixtures were analyzed by TG, DTA, FTIR and XRD techniques. The screening of polymorphic forms was performed through the solvent recrystallization methodology. The obtained crystals were characterized by TG, DSC, XRD, FTIR and MEV techniques. Thermal stability of dexamethasone was not altered by the excipients tested, as indicated by TG curves. DTA curves showed interactions signs with microcrystalline cellulose 101 and 102, magnesium stearate, mannitol and polyvinylpyrrolidone. Drug infrared absorption profile and XRD pattern were not altered in the binary mixtures, confirming that the interactions verified by DTA technique were probably heat-induced. Solvent recrystallization methodology produced solid samples of dexamethasone with different crystalline profiles, most of them associated with a mixture of polymorphic forms A and B. Based in our results, some of the tested excipients should be cautiously used in solid pharmaceutical dosages, especially those with heat-based manufacturing processes. Polymorphism screening pointed that different solvents and temperature conditions affect the crystalline structure of dexametaxone.