Desenvolvimento de complexos de inclusão bosentana-ciclodextrina e avaliação das características biofarmacêuticas.

Abstract

Pulmonary hypertension is a condition that affects the respiratory system, causing fatigue and exercise intolerance. In addition to being an incurable disease, its evolution is fast, and there are few effective options for treatment. The need for drugs to treat this disease and the growing interest of the medical class the knowledge of this disease prompted the study in this area, in order to search for therapeutic enhancement of currently available drugs for the treatment of pulmonary arterial hypertension. Because the bosentan a low solubility and bioavailability of drug, is interesting that pharmacotechnical methods are developed to provide improved absorption of this drug and potentiation of pharmacological activity of the therapeutic dose approved for the treatment of pulmonary hypertension. One of the available techniques for improving solubility and bioavailability of drugs is complexation with cyclodextrins used successfully in low aqueous solubility drugs. Thus, the intention of developing bosentan inclusion complexes with cyclodextrins is to promote better therapeutic use, increasing the effectiveness of the pharmacological treatment of patients with pulmonary hypertension. This research proposes the formation of bosentan inclusion complexes and cyclodextrins to increase drug solubility and improve the bioavailability of the drug, providing a differentiated ability to potentiate the treatment of pulmonary hypertension, can promote drug absorption, by optimizing the therapeutic effect and improving the quality of life of patients. The inclusion complex was prepared by several techniques, in solution, by physical mixing and spray-drier, evaluating the physico-chemical changes and characterization of the complex through the kinetic techniques, the stoichiometry of complexation, the solubility isotherms, spectrophotometry UV-VIS, solubility, DSC, TGA, infrared spectroscopy, electron microscopy in bright field and polarized light, apparent dissolution and dissolution profile. The results showed the formation of the inclusion complex due to changes in the characteristic peaks of the raw materials and increasing solubility, taking into consideration the conditions evaluated. The inclusion complex showed higher water solubility that the isolated bosentan, reinforcing the possibility that a formulation with the inclusion complex may have greater bioavailability in the organism.