Dynamic and Static Characteristics of Drug Dissolution in Supercritical CO2 by Infrared Spectroscopy: Measurements of Acetaminophen Solubility in a Wide Range of State Parameters

In this work we use infrared spectroscopy to investigate solubility properties of a bioactive substance in supercritical CO 2 (scCO 2 ). By using acetaminophen as a model compound, we show that the method can provide high sensitivity that makes it possible to study solubility at small concentrations, up to 10 –6 mol·L –1 . This method also allows one to investigate the kinetics of the dissolution process in supercritical solvent. Our measurements at two different points of the ( p, T ) plane ((40 MPa, 373 K) and (40 MPa, 473 K)) have shown significant difference in the kinetic mechanisms of acetaminophen dissolution at these two states: at higher temperature the dissolution process in scCO 2 has two steps: (i) “fast” step when the acetaminophen concentration in scCO 2 quickly reaches (70 to 80) % of the saturation level and (ii) a subsequent “slow” step where the acetaminophen concentration slowly increases up to the saturation level. However, at lower temperature, the dissolution process has only one, “slow” step.