Inhalable sustained release rifampicin microparticles: preparation and evaluation of in vitro and in vivo deposition

To increase the local therapeutic effect and reduce the systemic side effects of rifampicin (RIF), an anti-tuberculosis drug, lung targeting was investigated in the present study. Poly lactide-co-glycolide (PLGA) microparticles containing RIF were prepared by spray-drying method, mixed with an equal volume of lactose monohydrate (LAC) and delivered to the lung as a dry powder inhaler (DPI). Various ratios of ethyl acetate (EA), and dichloromethane (DCM) were used as solvent throughout the microparticle preparation. The use of large fractions of EA resulted in a slower evaporation rate and led to the formation of more spherical microparticles. Furthermore, the density of the microparticles and process yield increased, and release rate was reduced. In vivo experiments showed that changing the solvent of PLGA 75:25 from pure DCM to DCM/EA 67:33 mixture resulted in altering the Tmax value from 36 to 48 h, Cmax from 0.53 to 0.43 μg/mL, and local drug concentration at 60 h from 406 to 612 μg/gram tissue.