Hidróxidos Duplos Lamelares para a Co-entrega de amoxicilina e ibuprofeno: estudo da estabilidade e atividade Antimicrobiana

Abstract

Layered Double Hydroxides (LDH) are often described in the literature as a viable alternative for the encapsulation and carrying of drugs, since depending on the chemical composition, LDHs are biocompatible, chemically and thermally stable, in addition to exhibiting strong adsorption capabilities. and ion exchange. However, despite being potentially interesting, there are few studies that report the use of LDH in the simultaneous delivery (co-delivery) of different drugs. The co-delivery of active ingredients can represent advantages over conventional therapy, influencing bioavailability, stability, absorption and, eventually, synergy between the active ingredients. The present work aimed to study the stability, antimicrobial activity and modified release of amoxicillin (AMOX) and ibuprofen (IBU) present simultaneously in LDH. The LDHs of Zn/Al and Mg/Al and iron derivatives (HO-Fe) were prepared by coprecipitation at different temperatures (room and 75 0C) and pH (7.4, and 9), and the incorporations of AMOX and IBU to inorganic matrices were carried out by direct synthesis or by means of solid dispersions between drugs and inorganic matrix in the proportion 20% w/w (drug mass / inorganic solid mass). All compounds and dispersions were characterized by infrared spectroscopy (IR), scanning electron microscopy coupled to the dispersive energy spectrometer (SEM-EDS), thermogravimetric analysis (TG) and X-ray diffraction (XRD). The dosages of the drugs were performed by UV-vis spectroscopy and the antimicrobial activities of the solid dispersions were evaluated by colony counts through the inhibition of the Staphylococcus aureus bacteria. Preliminary studies have shown that the stability of AMOX is strongly influenced by the temperature and pH of the medium, regardless of whether it is in buffered solution or in solid dispersion. Differently, it was found for the IBU, which proved to be stable in the various conditions studied. The mode of incorporation of the active ingredients into the inorganic matrices, whether by direct synthesis or solid dispersion, did not influence the mode of release / solubilization of the drugs in buffer solution at pH 7.4, exhibiting greater than 50% desorption in up to 5 minutes of kinetics . However, the incorporations of AMOX and IBU by direct synthesis were not reproducible, in addition to exhibiting marked contamination by sodium chloride due to the preparation process. Thermogravimetric analyzes of the dispersions suggest that the inorganic matrices do not negatively affect the drugs, and that the IBU / AMOX co-presence is not harmful in terms of the thermal stability of the mixture. Under the conditions studied, LDH Zn/Al exhibited, when compared to other systems, a more pronounced action in inhibiting the growth of the microorganism, regardless of the presence of drugs. The results presented in this work open promising perspectives in the understanding and use of LDH and derivatives as host matrices of active principles in co-delivery systems.