Optimization of spray-drying process for perparation of inhalable rifampicin-loaded popy (d,l-lactide-co-glycolide) powder

Abstract

In this study, a 2⁴ full factorial design with center points was performed to investigate the influence of the following independent spray drying process parameters: inlet drying temperature (℃), aspirator control (%), pump setting (%) and nozzle gas flow setting (mm) on the properties of poly(d,l-lactide-co-glycolide) (PLGA) microparticles loaded with rifampicin. The rifampicin-PLGA micropaticles were obtained from spraying the mixed solution in a mini spray dryer. The process yield, mass median diameter, entrapment efficiency and dissolution at first 20 min were evaluated. First, the nozzle gas flow setting was found to be a main effect on the studied responses followed by inlet drying temperature, aspirator control, and pump setting. Full factorial design with center points revealed all process parameters did not effect on entrapment efficiency and dissolution at 20 min. This study aims to optimize the operating conditions to maximize process yield of inhalable rifampicin-PLGA microparticles. The optimal operation conditions thus were evaluated by response surface methodology. Central composite face centered (CCF) design showed quadratic model were adequate. A statistical optimization of the spray drying process parameters gave recommended conditions by using inlet drying temperature 55 ℃, aspirator control 100%, pump setting 10% and nozzle gas flow setting 33 mm. This experiment would to generate a process yield of 33.4517 % by weigh of microparticles with a mass median diameter of 3.1997 µm. Finally, the data form design experiment was used in defining the process design space. The design space has been evaluated considering the significant process parameters and the relative influence of each variable on the desired characteristics of PLGA microparticles loaded rifampicin: process yield not less than 30% and mass median diameter between 3 and 5 µm. It is shown that spray drying method can produce rifampicin-PLGA microparticles that high productivity and compliance of inhalable powder specifications