Optimization of Ciprofloxacin Hydrochloride Spray-Dried Microparticles for Pulmonary Delivery Using Design of Experiments

RAZUC, MARIELA; PIÑA, JULIANA; RAMÍREZ-RIGO, MARÍA V.

AAPS PHARMSCITECH

SPRINGER

Año: 2018

1530-9932

Ciprofloxacin is a broad-spectrum antibiotic for treatment of pulmonary diseases suchas chronic obstructive pulmonary disease and cystic fibrosis. The purpose of this workis to rationally study the spray-drying of ciprofloxacin in order to identify the formulationand operating conditions that lead to a product with aerodynamic propertiesappropriate for dry powder inhalation. A 24-1 fractional factorial design was applied toinvestigate the effect of selected variables (i.e., Ciprofloxacin hydrochloride (CIP)concentration, Drying air inlet temperature, Feed flow rate and Atomization air flowrate) on several product and process parameters (i.e., particle size, aerodynamicdiameter, moisture content, densities, porosity, powder flowability, outlet temperatureand process yield), and to determine an optimal condition. The studied factors had asignificant effect on the evaluated responses (higher p-value: 0.0017), except for themoisture content (p-value>0.05). The optimal formulation and operating conditionswere: CIP concentration 10 mg/mL, Drying air inlet temperature 110 °C, Feedvolumetric flow rate 3.0 mL/min and Atomization air volumetric flow rate 473 L/h. Theproduct obtained under this set has a particle size that guarantees access to the lung,a moisture content acceptable for dry powder inhalation, fair flowability and highprocess yield. The PDRX and SEM analysis of the optimal product showed acrystalline structure and round and dimpled particles. Moreover, the product wasobtained by a simple and green spray-drying method.