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, ICP-OES 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.
Development of a spray-drying method for the formulation of respirable microparticles containing ofloxacin-palladium complex.
PALAZZO, FRANCESCO;GIOVAGNOLI, Stefano;SCHOUBBEN, Aurelie Marie Madeleine;RICCI, Maurizio
2013
Abstract
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, ICP-OES 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
