Production of drug loaded microparticles by the use of supercritical gases with the aerosol solvent extraction system (ASES) process

Abstract

The aerosol solvent extraction system (ASES) uses a supercritical gas as non-solvent for an organic solution of drug and polymer in order to form microparticles by a flocculation process. Due to the miscibility of organic solvent and supercritical gas phase, microparticles with residual organic solvents below 30 ppm are formed. This principle was tested to encapsulate model drugs such as hyoscine butylbromide, indomethacin, piroxicam and thymopentin. As a carrier, the polymer poly-L-lactide was used. The resulting microparticles were investigated with regard to particle formation, morphology, particle size, size distribution, and drug loading. With decreasing, polarity of the incorporated drug, an increasing extraction occurs which lowers the drug loading of the microparticles. The extraction capacity of the gas phase depends on temperature and pressure which determines density and polarity of the gas. The obtained results show that the production conditions have to be optimized for each drug/polymer combination. Totally non-polar drugs are completely extracted together with the organic solvent, however, polar drugs, and here especially peptides and proteins, are easy to incorporate with the ASES process.