Development of a spray-drying method for the formulation of respirable microparticles containing ofloxacin–palladium complex

The purpose of this study was to produce low-releasing spray-dried polymeric microparticles (MP) useful to target alveolar macrophages in tuberculosis (TB) inhalation therapy.Ofloxacin (Ofx) was encapsulated as ofloxacin–palladium (Ofx–Pd) complex into poly dl-lactide (PLA) MP by spray-drying. Ofx–Pd was prepared according to a method previously reported. A D-optimal design was employed to optimize drug content (DC), aerodynamic diameter (dae) and span. dae was calculated coupling tap-density to particle size analysis. The MP were characterized by SEM, UV spectrophotometry, and DSC. In vitro drug release was performed in comparison to Ofx loaded PLA MP.The Ofx–Pd complex formed spontaneously with a 1:1 stoichiometry. Inlet temperature, drug loading and polymer concentration resulted the most influential. Optimal MP had span of 0.9, a round shape, dae of 2.5 μm, and DC of 30% (w/w). DSC and SEM analyses correlated with particle size. The optimized MP formulation showed a very low release at pH 7.4 compared to spray-dried Ofx loaded MP, the release increased slightly at lower pHs.Potentially inhalable MP were obtained by an optimized spray-drying process. The very low initial drug release at physiologic pH could be useful to target alveolar macrophages and to avoid systemic exposure.

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