Precipitation of fluticasone propionate microparticles using supercritical antisolvent

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

effect of vehicles on spray drying of rifampicin inhalable microparticles: in vitro and in vivo evaluation

The aim of this study was to evaluate the effect of solvents used in the spray drying and the aerodynamic properties of the rifampicin microparticles and pulmonary absorption of the microparticles. Different mixtures of dichloromethane and water were used as solvents for spray drying of rifampicin microparticles. The water to dichloromethane ratios were 25:75, 50:50, 75:25, 80:20, 90: 10 and 100:0. The solutions were dried at inlet temperature of 70 °C. The powder properties of the samples were examined by laser diffraction, scanning electron microscopy [SEM], helium densitometer and infrared spectroscopy [IR]. The aerosolization performance of these formulations was investigated using an Andersen cascade impactor. Pulmonary absorptions of formulations were examined by the in situ pulmonary absorption described by Enna and Schanker method. The plasma concentration time profiles of rifampicin were constructed 8 hours following the intravenous and the intrapulmonary administrations. The pharmacokinetics parameters, C[max], T[max], t[1/2] AUC, mean residence time [MRT], K[a] and K[e] were determined for each formulations. The T[max] values for the samples decreased by increase in the amount of water in the initial feed. The T[max] values for the spray dried samples from the different mixtures of dichloromethane and water were 60 [min] and 30 [min] respectively. The solvent mixture as the spray drying vehicle played an important role in the in vitro and in vivo lung deposition. The type of spray drying vehicle showed significant effect on the aerodynamic behavior and pharmacokinetic parameters of the particles. The pulmonary absorption of drug revealed the possibility of achieving the minimal inhibitory concentration [MIC] of the antibiotics. The spray drying vehicle only affected absorption patterns of the formulations and it did not have any effect on the elimination rat of particle