Preparation Of Ultra-Fine Ciprofloxacin And Its Application In DPI Formulations

Ciprofloxacin is a fluoroquinolone antibiotic which has been widely used to treat the infection disease in respiratory tract, urinary tract and gastrointestinal tract. And its antibiotic ability is irreplaceable compared with other antibiotics. The pulmonary delivery for ciprofloxacin can not only improve the bioavailability of ciprofloxacin administered orally but also overcome the limitation of the ordinary diliveries. So in recent year, the pulmonary delivery route of ciprofloxacin-dry powder inhalation has attracted much attention.The particle size reduction is a very effective method to improve the efficiency of pulmonary drug delivery.In this study, the preparation of ultra-fine ciprofloxacin particles has been researched. Two crystallization methods including reaction crystallization and the combination of reactive precipitation and anti-solvent precipitation have been throughly studied. The ultra-fined ciprofloxacin particles can be prepared by controlling the precipitation parameters which is also the fundation for pulmonary delivery. Meanwhile Spray drying is employed to obtain ciprofloxacin PSA particles whose volume density has been reduced obviously, and it is suitable for dry powder inhalation. Furthermore, the properties of as-prepared ciprofloxacin powders are assessed by multi-stage liquid impinger (MSLI), in a new formulation, dry powder inhaler (DPI).The result shows that, when using the combination of reactive precipitation and anti-solvent precipitation in which de-ionized water is applied as the anti-solvent, the needle-shaped ciprofloxacin particles in slurry can be obtained under the following conditions:the volume ratio of anti-solvent to reactant5:1, stirring speed at10000r/min, crystallization temperature10℃. When the slurry is vaccum dried at60℃, the ultra-fined particles of ciprofloxacin (1～2μm) can be prepared. Furthermore, after controlling the spray drying condition, ciprofloxacin dry powder can form the spherical particles in size of3～4μm no matter the short-rod shape particle about1μm in size in the filter cake is dispersed in water or ethanol. The powder obtained in ethanol has lower volume density, and its fine particle fraction (FPF) of ciprofloxacin is evaluated up to74.13%.The Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) analysis indicated that no chemical decomposition took place during the process, and crystal structure of the drug has not changed.