Carrier effect in development of rifampin loaded proliposome for pulmonary delivery: a quality by design study

Purpose: Pulmonary tuberculosis (TB) is a worldwide life-threatening infection. The recommended anti-TB regimen contains oral administration of classical first-line drugs such as rifampin for 6-24 months which often leads to low patient compliance due to high adverse effects; therefore, lung localized pulmonary delivery of anti-TB agents may be a suitable alternative. Proliposomes free-flowing powders are well-known carriers for lung delivery since they can form liposomes by hydration. Liposomes are safe and useful carriers for lung delivery due to their phospholipid structure. Methods: Porous lactose and mannitol as proliposome carriers were prepared by spray drying technique using sucrose and citric acid as templating agents. Design Expert® software was used to develop forty formulations based on the porous and non-porous carriers, which were characterized with respect to their weight yield, density, and flowability. Rifampin-loaded hydrated liposomes were produced and evaluated for size, morphology, loading capacity and encapsulation efficiency. The optimized proliposomes in vitro release and aerosolization properties were evaluated. Solid-state analysis was confirmed by differential scanning calorimetry (DSC). Results: Porous lactose surface area was 80 folds higher than non-porous one, respectively. Optimized porous-based proliposome indicated the acceptable aerosolization properties, including mass median aerodynamic diameter (MMAD) of 6.21 ± 0.36 µm and fine particle fraction (FPF) of 9.17 ± 0.18% with a fast rifampin release (80%) within one hour. DSC results proved that there was no change in the solid-state of rifampin during the production process. Conclusion: Hence, it seems; rifampin loaded inhalable proliposomes may be a suitable system for delivering liposomal rifampin into the lungs.