Desenvolvimento de complexos de inclusão multicomponentes com ácido ferúlico e obtenção de membrana para avaliação da liberação em formulações semissólidas

Abstract

Ferulic acid (FA) is a phytochemical constituent pat of the polyphenols group which are found mainly in rice and corn meal, with emphasis on its photoprotective and antioxidant activity. Thus, FA has been widely studied for application in photoprotective and anti-aging skin formulations. In the development of topical formulations, in vitro skin release assays present themselves as a fast, low-cost assay that enable preliminary results. The use of FA is limited by the instability of the molecule in the face of light and/or oxidation. In view of this, its stability can be improved through complexation with cyclodextrins, dispersion in polymers or inclusion in cyclodextrins followed by the association of a polymer forming a multicomponent system. Thus, the objective was to obtain a membrane model that is similar to the composition of human skin for in vitro skin release assays and development of multicomponent systems with cyclodextrins and hydrophilic polymers using ferulic acid. The membrane was obtained by impregnation of a lipid solution in synthetic membrane and characterized by Differential Exploratory Calorimetry (DSC), Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Gel and cream-gel formulations containing AF 0.5% (w/w) were evaluated for stability and in vitro release through the optimized membrane in franz diffusion cell. In the development of multicomponent complexes, studies of molecular dynamics and solubility in aqueous phase were carried out. After selection of cyclodextrin and polymer to make up the systems, they were obtained by the methods of kneading and evaporation rotary, characterized DSC and TG (thermogravimetry), X-ray diffraction (DR-X) and Fourier transform infrared spectroscopy (FTIR). In addition, they were evaluated for oxidative stability and antioxidant activity. The techniques used to characterize the obtained membrane allowed to demonstrate the occurrence of impregnation of the lipid solution. The formulations were stable when stored at 4 ºC ± 2 °C. The results of in vitro release using the optimized membrane suggest that it can be applied as an accessible and simple membrane in the in vitro release of active substances. Regarding the development of multicomponent systems, through characterization techniques it was possible to understand the interactions between FA, cyclodextrins and polymers. The techniques of obtaining the multicomponent systems were adequate, with high incorporation content of the asset. The method of obtaining by kneading was highlighted, which presented considerably higher yield when compared to the method by evaporation rotary. The cyclodextrins and polymers selected had the potential to be used in multicomponent systems. Since they increased the stability of FA against high temperatures, they also assisted in the transition from crystalline to amorphous state of the drug, due to the insertion of the active inside the cavity and interaction with the polymer. For oxidative stability, it was verified that the components of the system conferred significant stability for FA. In antioxidant activity, in general, multicomponent complexes enhanced FA activity. The results suggest the formation of stable multicomponent systems, enabling optimization to the asset. Providing subsidies for the incorporation of these systems in cosmetic formulations.