Solubilities of four macrolide antibiotics in supercritical carbon dioxide and their correlations using semi-empirical models

Accurate experimental determination of a solid drug’s solubility in supercritical fluids and its correlation is crucially important to the development of supercritical technologies for the pharmaceutical industry. In the present work, the solubilities of azithromycin, erythromycin, clindamycin and clarithromycin in supercritical carbon dioxide were measured at temperatures ranging from (308 to 348) K and pressures from (12.2 to 35.5) MPa using a static method. The mole fraction solubilities ranged from 2.7 × 10−5 to 11.46 × 10−5. The crossover region was observed for azithromycin, clarithromycin, clindamycin and erythromycin from 13.8 to 14.0 MPa, 15.0 to 15.2 MPa, 14.8 to 15.2 MPa and 16.8 to 17.1 MPa, respectively. Solubility data were correlated using four semi-empirical density-based models (Chrastil, Kumar, Johnston, Bartle and Mendez-Santiago and Teja models). The average absolute relative deviations ranged from 1.7 to 7.4; 2.07 to 8.1; 7.21 to 10.37 and from 5.13 to 9.44 for Chrastil, Bartle, K–J and M–T models, respectively. The results showed that by using three temperature-independent parameters these models can be applied for satisfactory solubility predictions at different pressures and temperatures. A comparison among the four models revealed that the K–J and Chrastil models gave much better correlation of the solubilities in comparison with other models. Using the correlation results, the heat of drug–CO2 solvation and that of drug vaporization was separately approximated in the range of −13.56 to −23.12 and 33.07–47.65 kJ mol−1. The correlation results showed good agreement with the experimental data.