Molecular Mechanism of Conformational Crossover of Mefenamic Acid Molecules in scCO₂

In this work, we studied conformational equilibria of molecules of mefenamic acid in its diluted solution in scCO2 under isochoric heating conditions in the temperature range of 140–210 °C along the isochore corresponding to the scCO2 density of 1.1 of its critical value. This phase diagram range totally covers the region of conformational transitions of molecules of mefenamic acid in its saturated solution in scCO2. We found that in the considered phase diagram region, the equilibrium of two conformers is realized in this solution. In the temperature range of 140–180 °C, conformer I related to the first, most stable polymorph of mefenamic acid prevails. In the temperature range of 200–210 °C, conformer II, which is related to the second metastable polymorph becomes dominant. Based on the results of quantum chemical calculations and experimental IR spectroscopy data on the mefenamic acid conformer populations, we classified this temperature-induced conformational crossover as an entropy-driven phenomenon

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 CO₂ (scCO₂). 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 (<i>p</i>,<i>T</i>) 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 scCO₂ has <i>two steps</i>: (i) “fast” step when the acetaminophen concentration in scCO₂ 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

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 CO2 (scCO2). 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 scCO2 has two steps: (i) "fast" step when the acetaminophen concentration in scCO2 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