ABSTRACT
The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 µm and 9.84 µm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.
Subject(s)
Aprepitant , Capsules , Particle Size , Povidone , Solvents , Capsules/chemistry , Povidone/chemistry , Solvents/chemistry , Aprepitant/chemistry , Solubility , Dimethylformamide/chemistry , Drug Liberation , Drug Compounding/methods , TemperatureABSTRACT
The objective of this study is to optimize the process parameters for preparing polystyrene (PS) PM2.5 particles by supercritical antisolvent (SAS) method. Toluene was selected as the solvent and supercritical carbon dioxide (SC-CO2) was used as the antisolvent. The Box-Behnken design-response surface method was applied to investigate the effect of crystallizer pressure, PS massic concentration, flow ratio of CO2/solution and crystallizer temperature on the size and the distribution of PS particles, systematically. It is found that crystallizer temperature is the most significant variable on the size and the distribution of PS particles, followed by flow ratio of CO2/solution and PS massic concentration, and crystallizer pressure is the slightest significant factor. The particle size increases with the increase of crystallizer temperature. The optimum conditions are obtained as crystallizer pressure 9.8 MPa, PS massic concentration 1.6 wt%, flow ratio of CO2/solution 140 g/g and crystallizer temperature 309 K. Under these conditions, the PS particle with the size of 2.78 µm and a narrow size distribution has been prepared, meeting PM2.5 standard aerosols. The results suggest that it is feasible to produce PM2.5 standard aerosols by SAS.
