Preparation of sustained release rifampicin microparticles for inhalation

The aim of this research was to develop a novel carrier-free dry powder formulation of rifampicin for inhalation with controlled-release properties.

Rifampicin dihydrate (RFDH) microcrystals were prepared by a polymorphic transformation of rifampicin. The prepared RFDH microcrystals were coated with poly (DL-lactide-co-glycolide) or poly (DL-lactide), using a spray-dryer equipped with two different types of three-fluid (3F) spray nozzles. The physicochemical and aerodynamic properties of the coated RFDH microcrystals were compared with those of conventional matrix microparticles.

The coated RFDH powder, encapsulating 50% of rifampicin, was successfully prepared by simple in-situ coating methods using two different types of 3F nozzles and had mass median aerodynamic diameter values of 3.5-4.5 µM. The thin flaky morphology of RFDH powders, providing good aerosolization properties, was maintained after coating. The coated RFDH formulations showed relatively low initial rifampicin release, compared with the uncoated RFDH crystals, followed by slow rifampicin release (about 70%) over 8 h in phosphate-buffered saline media (pH 7.4). Significant chemical degradations were not observed from the crystalline-structured RFDH formulations, while the amorphous-structured matrix formulations showed chemical degradation in six months.

These polymer coated RFDH formulations may be a valuable alternative in the treatment of tuberculosis since the carrier-free formulation offers the benefit of delivering a maximum-potency formulation of the antibiotic directly to the site of infection, and long drug residence times may be achieved by the controlled release of the drug.