Preparation and In-Vitro /In-Vivo Evaluation of Chitosan Based Microspheres as Respirable Slow Release Isoniazid Formulation

The present work was aimed to prepare respirable slow release formulation for isoniazid by spray drying method using hydrophilic carrier, chitosan. The chitosan microspheres were crosslinked with glutaraldehyde to modify release characteristics. Microspheres were prepared and evaluated for % yield, drug loading, moisture content, morphological characteristics, particle size, tapped densities, in vitro drug release, in vitro aerosolization and pharmacokinetic parameters. The scanning electron microscopy revealed that microspheres produced were spherical shaped with slight rough surface. The drug loading efficiency of microspheres showed drug loading efficiency was in the range of 84.44 % to 98.24 %. The in-vitro drug deposition revealed that mass median aerodynamic diameter of crosslinked chitosan microspheres (2.82 µm) was better than the uncrosslinked chitosan microspheres (3.85μm). The complete drug release was seen with uncrosslinked microspheres in two hour while crosslinked chitosan microspheres showed sustained drug release for more than 12 hrs. All the formulation batches showed Carr’s index in the range of 28.7 to 34.3 %. The fine particle fraction for crosslinked chitosan microspheres was found to be 69.1%. Pharmacokinetic differ among the free, crosslinked and uncrosslinked formulations. The crosslinked chitosan microspheres showed sustained drug release lasted for more than 3 days with half life of 31.67 hrs. In vitro and in vivo evaluation studies suggested that chitosan microspheres prepared with spray drying method showed promising aerosol properties having potential to use as sustained drug release formulation for isoniazid as inhalable microparticles.