Quality by design - Spray drying of ciprofloxacin-quercetin fixed-dose combination intended for inhalation

Spray drying is a well-suited technique for producing fixed-dose drug combinations. There has been a growing interest in utilizing spray drying to engineer carrier-free inhalable drug particles. The aim of this study was to understand and optimise the spray drying process of a ciprofloxacin-quercetin fixed dose combination intended for pulmonary administration. A 2^4-1 fractional factorial design and multivariate data analysis was used to identify important process parameters and investigate correlations with particle characteristics. The independent variables were solute concentration along with the processing parameters: solution flow rate, atomizing air flow rate and inlet temperature. The dependent variables included particle size distribution, yield and residual moisture content (RMC). Correlations between dependent and independent variables were further investigated via principal component analysis. Overall, solution flow rate, atomizing air flow rate and inlet temperature were found to affect the particle size D_(v,50) and D_(v,90) while the solute concentration and the atomizing air flow rate mainly affected the span. The inlet temperature was the most important parameter affecting the RMC and the yield. The formulation with optimized independent variables had a D_(v,50) and span values of 2.42 µm and 1.81 with excellent process yield >70% and low RMC i.e. 3.4%. The optimized formulation was further investigated for its in vitro aerosolization performance using next generation impactor (NGI); it exhibited high emitted dose (ED > 80%) and fine particle fractions (FPF > 70%) for both drugs.