Formulation Development of Lung Targeted Drug Delivery System for Treatment of Tuberculosis

Abstract

The main objective of present study was to achieve drug targeting into the lungs by developing dry powder inhaler (DPI) formulations. Two anti-tubercular drugs, rifampicin and bedaquiline were selected for the project owing to their high lipophilicity. The conventional and nanoparticle DPI formulations of both the drugs were prepared and evaluated. Numerous preliminary batches were prepared and the significant factors were optimized using Design of Experiment approach. The nanoparticles were prepared using ionic gelation probe sonication method and evaluated for particle size, zeta potential, entrapment efficiency and drug loading. Further, the nanoparticles were freeze-dried with lactose and formulated into DPI. The DPI formulations were evaluated for blend uniformity, content uniformity and fine particle fraction.. The optimized formulations were further characterized for SEM, DSC and XRD. In vitro cytotoxicity studies were also done on macrophage J774 cell lines. The % cell viability was the highest in nanoparticle DPI formulation. In vivo pharmacokinetic studies were performed in rat models, the nanoparticle DPI formulation showed the highest concentration in lungs in comparison to pure drugs as well as conventional DPI formulations of both the drugs. In vivo acute and chronic toxicity studies were also performed. The formulations were found safe in animal models. Therefore, developed DPI formulations could efficiently deliver the drugs into the lungs.