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

Abstract

Ciprofloxacin is a broad-spectrum antibiotic for treatment of pulmonary diseases such as chronic obstructive pulmonary disease and cystic fibrosis. The purpose of this work was to rationally study the spray drying of ciprofloxacin in order to identify the formulation and operating conditions that lead to a product with aerodynamic properties appropriate for dry powder inhalation. A 24 - 1 fractional factorial design was applied to investigate the effect of selected variables (i.e., ciprofloxacin hydrochloride (CIP) concentration, drying air inlet temperature, feed flow rate, and atomization air flow rate) on several product and process parameters (i.e., particle size, aerodynamic diameter, moisture content, densities, porosity, powder flowability, outlet temperature, and process yield) and to determine an optimal condition. The studied factors had a significant effect on the evaluated responses (higher p value 0.0017), except for the moisture content (p value > 0.05). The optimal formulation and operating conditions were as follows: CIP concentration 10mg/mL, drying air inlet temperature 110°C, feed volumetric flow rate 3.0mL/min, and atomization air volumetric flow rate 473L/h. The product obtained under this set had a particle size that guarantees access to the lung, a moisture content acceptable for dry powder inhalation, fair flowability, and high process yield. The PDRX and SEM analysis of the optimal product showed a crystalline structure and round and dimpled particles. Moreover, the product was obtained by a simple and green spray drying method.