Desenvolvimento de novos carreadores para fármacos a base de zeólitas: estudo das zeólitas Faujasita, Beta e Mordenita como ferramentas para liberação modificada de isoniazida e olanzapina

Abstract

Zeolites are aluminosilicates that present as one of their main characteristics pores and cavities of well-defined dimensions, high specific area and cation exchange capacity, conferring ability to sieve and store molecules, making them widely applied and studied for various purposes. Isoniazid is one of the drugs used to treat tuberculosis; an infectious and contagious disease that has a high worldwide mortality rate has high water solubility and low permeability. On the other hand, olanzapine is an antipsychotic agent used for the treatment of schizophrenia and diseases of mental disorder, presenting low solubility and little oral bioavailability. Considering these premises, this thesis has the central objective of studying the application of the synthetic zeolites Beta, Mordenite and Faujasita as tools in the technological improvement of the drugs isoniazid and olanzapine. For that, the zeolites and drugs were previously characterized and the parameters related to adsorption and release were evaluated. For the study conducted with isoniazid, adsorption kinetics were performed at different pH's, results that were adjusted to the Langergren mathematical models, the pseudo-second order equation and the intraparticle diffusion of the Weber and Morris model. Based on the kinetic results, adsorption isotherms were constructed, considering the most favorable pH and the time in which the adsorption equilibrium is reached, pH 3 and 4 hours for Faujasita and pH 6 and 10 hours for Beta, the data isotherm were adjusted to Langmuir and Freündlich mathematical models. Hybrid materials composed of each type of zeolite and isoniazid were formulated and characterized by several techniques and the hybrids composed with zeolites Faujasita and Beta studied regarding the release of isoniazid in two release media, acid medium and phosphate buffer, with the purpose of to evaluate if these hybrids are able to provide control over the release of isoniazid in these media. These results of the release kinetics were adjusted to the mathematical models of Korsmeyer-Peppas and Higuchi. In parallel, as a way to better understand the interactions between zeolite and isoniazid, molecular modeling studies were carried out, exploring classical molecular mechanics, applying force fields based on empirical interatomic potentials with a better fit for the drug zeolite system, COMPASS27. Adsorption studies were also conducted with olanzapine where the influence of pH, contact time and the initial concentration of the drug solution was evaluated, as well as a release study. The results showed that Beta and Faujasita zeolites showed the best retention capacity, where for Faujasita only a considerable adsorption of olanzapine is observed with a change in the pH of the medium to 6. For the study with olanzapine, it was also observed greater protection against thermal degradation and more resistance at the release in the acid medium of the drug retained from the zeolite.