Formulation and Evaluation of Novel Spray-dried Alginate Microspheres as Pulmonary Delivery Systems of Rifampicin in Rats

Abstract:

Background: Lung administration of anti-biotics in the dry powder form is promising for improved treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, an anti-tubercular drug encapsulated in particulate system in presence of β-cyclodextrin may improve lung delivery. Materials and Methods: Present study was aimed to evaluate the pharmacokinetic parameters of rifampicin loaded alginate spraydried microparticles administered by pulmonary route. Novel spray-dried sodium alginate microspheres were formulated with β-cyclodextrin to form bioadhesive microparticles for sustained release of rifampicin. The particles without β-cyclodextrin and without drug were also prepared. Intratracheal instillation was adopted for lung delivery in comparison with oral delivery of pure drug. Results: Around 75% microspheres were in the respirable range, with satisfied aerodynamic characteristics. Aqueous solubility and skin permeation of rifampicin were increased significantly in presence of β-cyclodextrin. The in vitro antimycobacterial activity of the formulation showed enhanced activity in presence of β-cyclodextrin. The relative bioavailability of rifampicin alginate microspheres administered by pulmonary route was significantly higher when compared to that of oral route indicating the therapeutic potential of microspheres as a promising alternative to the presently available oral route. Conclusion: Along with sustained release of drug from the particulate formulation, the presence of cyclodextrin has the potential to achieve higher therapeutic efficacy by increasing the solubility and permeation of rifampicin.

Key words: Alginate, Aerodymanic Characteristics, β-cyclodextrin, Intratracheal instillation, Pulmonary drug delivery, Spray-dried microspheres.