Hydrophilic versus hydrophobic porogens for engineering of poly(lactide-co-glycolide) microparticles containing risedronate sodium

Abstract

Objective: The aim of this study was to investigate the effect of two mechanistically different porogens, namely: the hydrophilic hydroxy-propyl-β-cyclodextrin and the hydrophobic porogens (mineral oil and corn oil) in producing open/closed pored engineered polylactide-co-glycolic-acid microspheres suitable for pulmonary delivery of risedronate sodium (RS).Materials and methods: Surface morphology of the microspheres was studied and they were characterized for entrapment efficiency (%EE), particle size, and porosity as well as aerodynamic and flow properties. Selected formulae were investigated for in vitro drug release and deposition behavior using next generation impactor. Furthermore, the safety of the free drug and the selected prepared systems was assessed by MTT viability test performed on Calu-3 cell line.Results and discussion: The current work revealed that HP-β-CD produced open-pored microspheres, while oils produced closed pored microspheres. Modulation of preparation parameters generated porous RS microspheres with high %EE, sustained drug release profile up to 15 days, suitable geometric and aerodynamic particle sizes and excellent flow properties. The safety of HP-β-CD systems was higher than the systems utilizing oil as porogen.Conclusion: Porogen type affected the behavior of the microspheres as demonstrated by the various characterization experiments, with microspheres prepared using HP-β-CD being superior to those prepared using oils as porogens.