Development and evaluation of a new semi-empirical model forcorrelation of drug solubility in supercritical CO_2

摘要

The accurate determination of drug solubility in supercritical fluids and its correlation are crucially impor-tant for development of supercritical technology in pharmaceutical industries. In this research, a newempirical equation was proposed to correlate solute solubility with temperature, pressure and densityof pure supercritical CO_2. The accuracy of the proposed model in comparison with six other empiricalequations was evaluated using 25 published solubility data sets by calculating the average absolute rela-tive deviation (AARD). Due to these data sets, the mean AARD for the proposed model was 10.64 (±4.18);where, the values for other equations were 13.97 (±6.79), 13.16 (±6.31), 13.33 (±5.36), 14.64 (±13.94),29.62 (±20.28) and 12.64 (±6.04). To validate proposed model, the solubility of Clobetasol Propionate(CP) and Desoxycorticosterone acetate (DC) as two corticosteroids was measured and modeled at tem-peratures ranging from 315 to 345 K and pressures from 152 to 305 bar by a static method. The acquiredmole fraction results varied in the range of 1 × 10~(?6)to 2.1 × 10~(?5)for CP and 5 × 10~(?6)to 1.03 × 10~(?4)for DC.The AARD of proposed model for CP solubilities was 4.95% and for DC was 5.29% that was in reasonablerange according to other published solubility data.