Polyhydroxy acids [poly(L‐lactic acid) (L‐PLA),poly(D,L‐lactic acid) (DL‐PLA), and poly(glycolic acid) (PGA)], biocompatible and bioerodible polymers that are being investigated for controlled delivery of pharmaceuticals and are approved by the Food and Drug Administration for in vivo sutures and bone repair implants, have been dissolved in supercritical CO2 and precipitated by rapid expansion of the resulting supercritical solutions (RESS). The formation of these microparticles and microspheres is a first step toward the goal of producing, in a single processing step, drug‐loaded polymeric microspheres for use in controlled release applications. Nucleation of poly(L‐lactic acid) from CO2 and CO2‐acetone mixtures produced microparticles and microspheres ranging from 4 to 25 μm. Microspheres (2‐20 μm) were also obtained with chlorotrifluoromethane as solvent. Commercial L‐PLA precipitated after extraction of low molecular weight oligomers showed degradation kinetics similar to that of the starting material. The precipitation of DL‐PLA from CO2 produced irregular‐sized particles (10‐20 μm). PGA, a polymer insoluble in most organic solvents, was found to be soluble in supercritical CO2. Nucleation of PGA from CO2 produced both regular‐sized particles and needles of 10–40‐μm length. The total solubility of commercial L‐PLA in supercritical CO2 at 250 bar and 55 °C decreased from 0.14 wt % to less than 0.05 wt % and then leveled off as the cumulative flow of CO2 per unit mass of L‐PLA loaded in the extractor increased beyond 20 standard L of CO2/g of L‐PLA. Use of acetone (1 wt %) as a cosolvent increased L‐PLA solubility by ∼500%.
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