Abstract

Tuberculosis (TB) is a serious infectious disease that affects more than new 10 million patients each year. Many of these cases are resistant to first-line drugs so second-line ones, like fluoroquinolones, need to be incorporated into the therapeutic. Ofloxacin (OF) is a fluoroquinolone which demonstrates high antibiotic activity against the bacteria that causes TB (M. tuberculosis). In this work, ionic complexes, composed by hyaluronic acid (HA) and OF, with different neutralization degrees, were prepared and processed by spray drying (SD) to obtain powders for inhalatory administration. Combining a formulation with high neutralization degree, high SD atomization air flowrate and the use of a high-performance collection cyclone, very good process yields were obtained. Carrier-free formulations with a loading of 0.39–0.46 gOF/gpowder showed excellent emitted, fine particle, and respirable fractions for capsule loadings of 25 and 100 mg. The ionic complexes demonstrated higher mucoadhesion than pure OF and HA. The best formulation did not affect CALU-3 cell viability up to a dose 6.5 times higher than the MIC90 reported to treat multi-drug resistant TB.

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