Desenvolvimento e avaliação de formulações mucoadesivasbucais incorporadas com complexos de inclusão β-ciclodextrinae fármacos antifúngicos

Abstract

Several conditions of the oral cavity, such as periodontitis, stomatitis, gingivitis and ulcers are usually treated with topical oral formulations. These formulations have the advantage of reducing the degree of systemic side effects, but the main disadvantage is the short period of permanence in the applied site, requiring repeated applications to obtain adequate levels of drug concentration. Mucoadhesives as a drug delivery system are a trend in pharmaceutical technology, as they can act directly at the site of infection, in a lower dose and for a determined time. With this, it is possible to have a significant impact on the treatment since this system has the effect of optimizing the bioavailability of therapeutic agents and a prolonged action time at the administration site, in addition to the faster absorption of the drug in local tissues. Inclusion complexes with cyclodextrins have been suggested to increase the drugs' solubility and stability, aiming to optimize the action of antifungal and antiseptic drugs such as nystatin and chlorhexidine in the oral mucosa. Given this framework, this study aimed to develop and characterize mucoadhesive gels containing nystatin (Nys) or chlorhexidine (Clx) pure or complexed with β-cyclodextrin (βCD) for the treatment of oral conditions. Mucoadhesive gels formulated using chitosan and hydroxyethylcellulose polymers were developed and tested for the incorporation of pure or complexed drugs. Characterization involved mucoadhesion, residence time, spreadability, rheology, and stability tests in determining the composition of the formulations. After drug incorporation, the formulations were evaluated according to their rheological properties in an oscillatory rheometer, bioadhesive properties in texturometer, in vitro release, and permeation in vertical Franz diffusion cells. The results showed that the gels are stable and have mucoadhesive properties and elastic behavior capable of increasing retention at the application site, which is essential for the drug to remain in contact with the mucosa for a more extended period. There was a considerable increase in the speed of dissolution of the drugs in the inclusion complexes compared to their pure form and low permeation, indicating that the drug should act in the oral mucosa. Thus, mucoadhesive gels are a promising alternative for the treatment of oral disorders, by increasing the contact time of the formulation with the oral mucosa and the greater

bioavailability of these drugs caused by the formation of inclusion complexes with β- cyclodextrin.