Desenvolvimento de formulações pediátricas contendo tuberculostáticos

Abstract

The availability of pediatric formulation for treating tuberculosis is a reality for the countries of Asia and Africa, but not in other countries that have considerable incidence of this disease. Considering the situation of the global need for medicines for pediatric use and specifically for this type of product for the treatment of tuberculosis, whose drugs association represents a major challenge, this study aimed to develop oral formulations containing rifampicin, isoniazid and pyrazinamide in fixed-dose combination for pediatric use. It began with the physico-chemical characterization of active ingredients (identification by IR, UV and HPLC, determination of content by HPLC and UV, bulk density and angle of repose). It then carried the evaluation of thermal compatibility of active ingredients with different excipients (DSC and TG); the vehicle development for use as a carrier of oral drugs in children with minimal components, at low concentrations, selecting them from the inputs considered safe for children (evaluating viscosity, pH, palatability, physical and microbiological stability). It was developed and validated spectrophotometric analytical methodology for use in the assay and dissolution profile of three drugs in the developed products, in addition to pre-formulation studies by apparent density and angle of repose of the individual drugs and their mixtures with aerosil, granulation with different polymers and their effect on the release of rifampicin, rifampicin stability in function of pH, coating and microencapsulation of rifampicin with chitosan, and finally the development of solid oral formulations in the form of powder for reconstitution and dispersible tablet containing a fixed-dose combination of rifampicin, isoniazid and pyrazinamide. We evaluated the viscosity, pH, content of drug and stability of the reconstituted preparations, as well as average weight, hardness, disintegration time, dissolution profile and friability of the tablets. The Ozawa method was used for DSC studies kinetic to estimate the frequency factor, the activation energy and the order of reactions that lead to degradation of solid dosage forms. The two solid dosage forms when dispersed in water, resulting in pseudo-plastic suspension easy to be handled, measured and administered, and can be used for up to 12 hours after reconstitution.