Purpose. The antibiotic therapy for a direct administration to the lung in cystic fibrosis patients has to provide suitable availability, possibly in the lower respiratory tract, characterized by the presence of thick secretions. Because of this problem, one of the crucial step in the therapeutical management of the respiratory disease could be the drug solubilization directly in this site of action. The aim of the study was to obtain respirable powders of clarithromycin, while improving drug aqueous solubility. Methods. Several batches of micronized particles were prepared by spray drying different feed solutions, varying the solvent composition (water/isopropyl alcohol ratio), the drug concentration and pH of the liquid feeds. Particle size distribution of raw materials and engineered particles was determined using a light-scattering laser granulometer while particle morphology was assessed by scanning electron microscopy. The in vitro deposition of the micronized clarithromycin powders was evaluate by means of a Single-Stage Glass Impinger (SSGI; apparatus A, European Pharmacopoeia 8.0), using a Turbospin® as device for the aersolization. True density measurements were performed by a helium pycnometer (Accupyc II 1340). Solubility measurements of raw and spray-dried drug were carried out at 37°C in phosphate buffer (0.05 M, pH 6.8). Results. Morphology and aerodynamic properties of spray-dried particles were strongly influenced by organic solvent concentration and pH of the liquid feeds processed, both modifying drug solubility. Spherical particles and crystals were obtained at higher pH and lower organic solvent content, while wrinkled particles were obtained at lower pH values. Moreover, thanks to their shape, spray-dried powders from hydro-alcoholic solutions containing clarithromycin in its salt form, showed better aerodynamic properties. Conclusions. The clarithromycin inhalable powders containing the drug in its salt form, showed high water solubility and good aerodynamic properties, thanks to a fine-tuning of the process parameters and liquid feed composition, with no need to add any excipients.
Drug solubility and aerodynamic properties of dry powders prepared by spray drying: clarithromycin versus its chlorohydrate salt
MANNIELLO, MICHELE DARIO;DEL GAUDIO, Pasquale;AQUINO, Rita Patrizia;RUSSO, Paola
2015-01-01
Abstract
Purpose. The antibiotic therapy for a direct administration to the lung in cystic fibrosis patients has to provide suitable availability, possibly in the lower respiratory tract, characterized by the presence of thick secretions. Because of this problem, one of the crucial step in the therapeutical management of the respiratory disease could be the drug solubilization directly in this site of action. The aim of the study was to obtain respirable powders of clarithromycin, while improving drug aqueous solubility. Methods. Several batches of micronized particles were prepared by spray drying different feed solutions, varying the solvent composition (water/isopropyl alcohol ratio), the drug concentration and pH of the liquid feeds. Particle size distribution of raw materials and engineered particles was determined using a light-scattering laser granulometer while particle morphology was assessed by scanning electron microscopy. The in vitro deposition of the micronized clarithromycin powders was evaluate by means of a Single-Stage Glass Impinger (SSGI; apparatus A, European Pharmacopoeia 8.0), using a Turbospin® as device for the aersolization. True density measurements were performed by a helium pycnometer (Accupyc II 1340). Solubility measurements of raw and spray-dried drug were carried out at 37°C in phosphate buffer (0.05 M, pH 6.8). Results. Morphology and aerodynamic properties of spray-dried particles were strongly influenced by organic solvent concentration and pH of the liquid feeds processed, both modifying drug solubility. Spherical particles and crystals were obtained at higher pH and lower organic solvent content, while wrinkled particles were obtained at lower pH values. Moreover, thanks to their shape, spray-dried powders from hydro-alcoholic solutions containing clarithromycin in its salt form, showed better aerodynamic properties. Conclusions. The clarithromycin inhalable powders containing the drug in its salt form, showed high water solubility and good aerodynamic properties, thanks to a fine-tuning of the process parameters and liquid feed composition, with no need to add any excipients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
