Sub-micrometer-sized biodegradable particles of poly(L-lactic acid) via the gas antisolvent spray precipitation process.

Sub-micrometer-sized particles of poly(L-lactic acid) may be formed by using near-critical or supercritical carbon dioxide as an antisolvent to precipitate poly(L-lactic acid) from droplets of methylene chloride solution sprayed into a carbon dioxide continuous phase. Particle sizes may be controlled by varying the density of the carbon dioxide; at constant temperature in the supercritical region, higher carbon dioxide densities yield larger particles. Two methods (one batch and one continuous) for introducing the poly(L-lactic acid) solutions into carbon dioxide are demonstrated. Although the two methods use very different mechanisms for forming the droplets, similar particle sizes are observed as a function of carbon dioxide density. We suggest that mass transport, rather than jet breakup and hydrodynamics, controls particle sizes in the near-critical and supercritical regions.