Precipitation of fluticasone propionate microparticles using supercritical antisolvent

ABSTRACT

The ability of supercritical fluids [SCFs], such as carbon dioxide, to dissolve and expand or extract organic solvents and as result lower their solvation power, makes it possible the use of SCFs for the precipitation of solids from organic solutions. The process could be the injection of a solution of the substrate in an organic solvent into a vessel which is swept by a supercritical fluid. The aim of this study was to ascertain the feasibility of supercritical processing to prepare different particulate forms of fluticasone propionate [FP], and to evaluate the influence of different liquid solvents and precipitation temperatures on the morphology, size and crystal habit of particles. The solution of FP in organic solvents, was precipitated by supercritical carbon dioxide [SCCO[2]] at two pressure and temperature levels. Effects of process parameters on the physicochemical characteristics of harvested microparticles were evaluated. Particle formation was observed only at the lower selected pressure, whilst at the higher pressure, no precipitation of particles was occurred due to dissolution of FP in supercritical antisolvent. The micrographs of the produced particles showed different morphologies for FP obtained from different conditions. The results of thermal analysis of the resulted particles showed that changes in the processing conditions didn't influence thermal behavior of the precipitated particles. Evaluation of the effect of temperature on the size distribution of particles showed that increase in the temperature from 40 °C to 50 °C, resulted in reduction of the mean particle size from about 30 micro m to about 12 micro m. From the results of this study it may be concluded that, processing of FP by supercritical antisolvent could be an approach for production of diverse forms of the drug and drastic changes in the physical characteristics of microparticles could be achieved by changing the type of solvent and temperature of operation