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 formed by the union of TO4 units where the T atom is usually Si and Al. These solids have, as one of their main characteristics, well-defined pores and cavities, high specific areas and cation exchange capacity, conferring sieving ability and storage of molecules. These properties mean that these materials have recently been widely applied and studied for several purposes, among them applications that aim to improve medicines, treatments and diagnosis of diseases. Considering these premises, this thesis has the central objective of studying the application of the synthetic zeolites Beta, Mordenite and Faujasita, already industrially consolidated, as tools in the technological improvement of the drugs isoniazid and olanzapine. Isoniazid is one of the drugs used to treat tuberculosis, an infectious disease that has a high worldwide mortality rate. Isoniazid is a bactericide that has high water solubility and low permeability. On the other hand, olanzapine is an antiphysical agent used for the treatment of schizophrenia and diseases of mental disorder, presenting low solubility and little oral bioavailability. In the search for a more efficient use of these drugs, this thesis studies the development of new carriers based on zeolites to be used in their modified release. 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 balance is reached, pH 3 and 4 hours for Faujasita and pH 6 and 10 hours for Beta, the results obtained were adjusted to mathematical models by Langmuir and Freündlich. 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, in order to to evaluate whether or not these hybrids can provide control over the release of isoniazid in these media. These results of the release kinetics were adjusted to the Korsmeyer-Peppas and Higuchi mathematical models. 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 better adjustment for the drug zeolite system, COMPASS27. Adsorption studies were also conducted with olanzapine where the influence of pH, contact time and 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 release in acid medium.