Sub‐Micrometer‐Sized Biodegradable Particles of Poly(L‐Lactic Acid) via the Gas Antisolvent Spray Precipitation Process

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Abstract
Sub‐micrometer‐sized particles of poly(L‐lactic acid) may be formed by using nearcritical 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.