Formulation, characterization and evaluation of inhalable effervescent dry powder of Rifampicin nanoparticles

Dry powder inhaler is a popular approach to pulmonary drug delivery to treat tuberculosis. Spray dried Nanoparticles using lactose carrier is extensively used for pulmonary drug delivery. Though lactose nanoparticles show deep lung deposition, they fail to uniformly disperse nanoparticles in its original form in alveoli. Rifampicin is one of the first line drugs in tuberculosis treatment. Lung targeted drug delivery system is an approach to reduce dose related side effects of rifampicin. Inhalable nanoparticles also help to target alveolar macrophages, thus improving treatment efficiency.

This study focuses on rifampicin nanosuspension formulation and optimization using nano-precipitation method followed by characterizing effervescent DPI of rifampicin nanoparticles with effervescent pair (citric acid and sodium bicarbonate). Preliminary studies showed suitability of 4:5 solvent: antisolvent ratio and lecithin (1%) as stabilizer. The drug and stabilizer concentration in nanoparticles was successfully optimized using 3 ∗ 2 factorial design using DESIGN EXPERT software. The rifampicin nanoparticles were further converted to spray dried powder using effervescent carrier.

The effervescent pair formulation was monodisperse and had a particle size of 1.5 microns (polydispersity index 0.289), thus showing better redispersibility than lactose nanoparticles. The mass median aerodynamic diameter and fine particle diameter of both spray dried formulations were similar and suitable for deep lung deposition.

These findings are suggestive that effervescent technique can be successfully employed to improve redispersibility of rifampicin nanoparticles.