Partitioning of drug model compounds between poly(lactic acid)s and supercritical CO2 using quartz crystal microbalance as an in situ detector

Quartz crystal microbalance (QCM) was used as an in situ detector to investigate the potential application in the phase equilibrium determination of supercritical CO₂-drug-polymer systems. CO₂ solubility in two biodegradable polymers, poly(d,l-lactic acid) (d,l-PLA) and poly(l-lactic acid) (l-PLA) was primarily measured at 313.15 K and pressures up to 10.0 MPa. d,l-PLA showed a better CO₂ absorption ability due to its amorphous structure. Four drug model compounds of poor solubility in water, ibuprofen, aspirin, salicylic acid and naphthalene were selected as representatives for the examination of drug uptake in PLA matrices, as well as partition coefficient during supercritical impregnation. It was found that partition coefficients of drugs can reach as high as 10³-10⁴ orders of magnitude and greatly affected by the intermolecular interactions between drugs and PLA. Aspirin exhibited the best partitioning during the supercritical impregnation at pressures of 8.0-10.0 MPa due to the existence of carboxylic acid and acetyl groups. Drug partitioning is additionally related to the drug concentration in ScCO₂, i.e. salicylic acid showed little absorption in PLA according to its poor solubility in ScCO₂ at 7.5-8.0 MPa, whereas the well CO₂-soluble compound, naphthalene, exhibited a moderate partition coefficient although its polarity was different from l-PLA.