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

Abstract

• Lenalidomide (LND) solubility in supercritical CO 2 (sc-CO 2 ) was measured for the first time. • Solubility data were correlated by different density-based models. • Experimental data was also correlated by Modeified Wilson and SRK models. • The accuracy of the models was evaluated by statistical criteria (AARD %), ( Radj ). • Thermodynamic enthalpies of Lenalidomide were estimated. 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-CO 2 )- based process requires accurate data on the drug solubility in sc-CO 2 . In this study, the solubility of Lenalidomide (LND), an anti-cancer, was experimentally determined in sc-CO 2 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 × 10 −4 –1.08 × 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-CO 2 with high accuracy. However, the SRK-EoS did not show acceptable accuracy in the correlation of LND solubility in sc-CO 2 . 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 ( Δ H total ) as well as vaporization ( Δ H vap ), and solvation ( Δ H sol ) enthalpies were computed.