Manipulation of particle size distribution of poly(L-lactic acid) nanoparticles with a jet-swirl nozzle during precipitation with a compressed antisolvent

The precipitation with a compressed-fluid antisolvent (PCA) process is a useful technique for producing biodegradable polymer microparticles for controlled drug delivery applications. Based on the mechanism that particles precipitate from a gaseous jet rather than atomized liquid droplets, we have designed and manufactured a nozzle capable of producing nanoscale poly(L-lactic acid) (PLLA) particles during PCA processing. A key design feature of the nozzle is the combination of a swirl flow and a micro-mixing swirl chamber to optimize gas-like mixing between the solvent and compressed antisolvent. Increasing the power input into the swirl chamber from 1.9 X 10(6) to 6.5 x 10(9) W/m(3) acts to enhance the degree of mixing occurring within the confines of the swirl chamber. This is shown by a reduction in jet mixing length from 2627 +/- 14 to 0 mum and a decrease in the average particle diameter of 100 000 M.W. PLLA from 1430+/-90 to 193+/-20 nm (volume weighted diameter). Nozzles designed to optimize gas-like mixing are inherently different from conventional PCA spray nozzles, and allow production of nanoscale PLLA particles with a sharper size distribution than previously attainable. (C) 2002 Elsevier Science B.V. All rights reserved.