In this work, we studied the conformational equilibria of lidocaine molecules released from NCC-based aerogel that was preliminarily impregnated with lidocaine. The doping of the aerogel with lidocaine was carried out in a saturated lidocaine solution in scCO2 at a temperature of 80 °C and a pressure of 200 bar. The conformational equilibria of lidocaine molecules in the scCO2 phase were examined over a temperature range of 35–80 °C along isochores corresponding to a scCO2 density equal to 1.1 of its critical value. We found that in the scCO2 phase, two stable conformers are predominantly realized. These conformers are characterized by the presence of a thermostable intramolecular hydrogen bond, with the difference between them being the mutual orientation of the two ethyl groups in the structure of the flexible −CH2−N<(C2H5)2 molecular fragment. We also discovered that the equilibrium concentration of lidocaine released from the aerogel into the scCO2 phase is lower than that of the saturated solution over the studied temperature range. Moreover, the presence of aerogel makes the crossover behavior of solubility less pronounced. By comparing the obtained data with those from our previous work, we found a similarity between the effects of aerogel presence and the rise in CO2 density in the case of saturated lidocaine solution.
