Experimental analysis and thermodynamic modelling of lenalidomide solubility in supercritical carbon dioxide

Reduction of the size of pharmaceutical particles to micro/nano scale is an approved strategy to enhance their dissolution rate at decremented side effects. Production of drug micro/nanoparticles via a supercritical carbon dioxide (sc-CO2)-based process requires accurate data on the drug solubility in sc-CO2. In this study, the solubility of Lenalidomide (LND), an anti-cancer, was experimentally determined in sc-CO2 at various temperatures (308-338 K) and pressures (120-300 bar). Furthermore, the obtained solubility data were correlated by different theoretical methods. LND solubility, in terms of mole fraction, was obtained in the range of 0.02 x 10(-4)-1.08 x 10(-4) depending on the conditions. The empirical models with different adjustable parameters, Soave-Redlich-Kwong equation of state (SRK-EoS) with two parameters van der Waals (vdW2) mixing rule, and expanded liquid theory (modified Wilson's model) were applied for experimental data correlation. According to the results, modified Wilson's model can correlate LND solubility in sc-CO2 with high accuracy. However, the SRK-EoS did not show acceptable accuracy in the correlation of LND solubility in sc-CO2. Among the empirical models, Alwi and Garlapati, Sung and Shim, Ch and Madras, Hozhabr et al., Garlapati and Madras, Keshmiri et al., Sparks et al., Reddy and Garlapati, Bian et al. (2011) and Belghait et al. showed R-adj values higher than 0.99 and produced the best correlation with 3,4, 5, 6 and 8 adjustable parameters, respectively. Moreover, the approximate values of total mixing heat (Delta H-total) as well as vaporization (Delta H-vap), and solvation (Delta H-sol) enthalpies were computed. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

This study experimentally determined the solubility of the anti-cancer drug Lenalidomide in supercritical carbon dioxide (sc-CO2) and analyzed the data using different theoretical models. The results showed that the modified Wilson's model provided an accurate correlation for the solubility of LND in sc-CO2, while the SRK-EoS did not show satisfactory accuracy.