Spray-drying of konjac glucomannan to produce microparticles for an application as antitubercular drug carriers

Spray-drying is proposed in this work as the technique to produce konjac glucomannan microparticles aimed at an application in lung tuberculosis therapy. Microparticles were developed to provide direct lung delivery of an association of two first-line antitubercular drugs, isoniazid and rifabutin, by inhalation. Mannitol or leucine were incorporated as spray-drying excipients to verify their effect on the final properties of drug-loaded konjac glucomannan microparticles. The obtained results indicate that konjac glucomannan is a suitable material for the preparation of inhalable microparticles for antitubercular therapy upon processing by spray-drying. The incorporation of excipients revealed no benefit on the characterised properties. Isoniazid and rifabutin were mostly associated to microparticles with success (efficiencies of 88-104%). However, the presence of mannitol was found to decrease the capacity to associate isoniazid (efficiency of 43%). The excipients further promoted the acceleration of drug release. Moreover, general absence of toxicity was observed for microparticles in Calu-3 and A549 cells, with cell viabilities above 70%. The results of the work suggest that microparticles composed only of KGM display the most appropriate characteristics.PEst-OE/QUI/UI4023/2011; SFRH/BD/115628/2016