Polymeric Microparticles: Synthesis, Characterization and In Vitro Evaluation for Pulmonary Delivery of Rifampicin

Abstract

Rifampicin, a potent broad-spectrum antibiotic, remains the backbone of anti-tubercular therapy. However, it can cause severe hepatotoxicity when given orally. To overcome the limitations of the current oral therapy, this study designed inhalable spray-dried, rifampicin-loaded microparticles using aloe vera powder as an immune modulator, with varying concentrations of alginate and L-leucine. The microparticles were assessed for their physicochemical properties, in vitro drug release and aerodynamic behavior. The spray-dried powders were 2 to 4 µm in size with a percentage yield of 45 to 65%. The particles were nearly spherical with the tendency of agglomeration as depicted from Carr’s index (37 to 65) and Hausner’s ratios (>1.50). The drug content ranged from 0.24 to 0.39 mg/mg, with an association efficiency of 39.28 to 96.15%. The dissolution data depicts that the in vitro release of rifampicin from microparticles was significantly retarded with a higher L-leucine concentration in comparison to those formulations containing a higher sodium alginate concentration due to its hydrophobic nature. The aerodynamic data depicts that 60 to 70% of the aerosol mass was emitted from an inhaler with MMAD values of 1.44 to 1.60 µm and FPF of 43.22 to 55.70%. The higher FPF values with retarded in vitro release could allow sufficient time for the phagocytosis of synthesized microparticles by alveolar macrophages, thereby leading to the eradication of M. tuberculosis from these cells.