Carrier‐free dry powder ofloxacin formulation for multi-resistant tuberculosis treatment

Abstract

Tuberculosis (TB) is a serious infectious disease worldwide. More than new 10 million patients are diagnosed each year in the world. Many of these new cases are resistant to first line antibiotics so second line ones, like fluoroquinolones, are incorporated to the therapeutic. Ofloxacin (OF) is a fluoroquinolone with high antibiotic activity against M. tuberculosis. In this work, microparticles composed by OF and the polyelectrolyte hyaluronic acid (HA) were developed by spray drying (SD) to be administered by inhalatory administration. SD aqueous feeds were prepared by neutralizing HA acidic groups at two different percentages (75 and 100%) with OF cationic groups. The SD operating variables were: air inlet temperature (co-current) of 140°C, feed solution flowrate of 6mL/min, 742L/h of atomization air flowrate and a drying air flowrate of 35m3/h. A high-performance cyclone was used to collect the microparticles. The combination of the selected atomization air flowrate and high-performance collection cyclone allowed obtaining good process yields (around 65%) and particles with small diameters (ca. 3.75m). To assess formulations aerodynamic behavior, microparticles were assayed in a next generation impactor (NGI). The SD products exhibited emitted fractions higher than 90% without the need of bigger carrier particles. Also, SD powders showed excellent fine particle (50%) and respirable fractions (30%). This indicates that a high proportion of the OF loading would be able to reach the lung and the macrophages to treat the infection. The formulations did not affect CALU-3 cell viability in an MTT colorimetric assay.