Gas Antisolvent Recrystallization of Paracetamol from Acetone Using Compressed Carbon Dioxide as Antisolvent

Abstract

Paracetamol was precipitated from solution in acetone using compressed carbon dioxide (CO2) as an antisolvent in a batch gas antisolvent (GAS) recrystallization process. In this study, the effect of specific carbon dioxide addition rate (0.067−6.0 min-1), temperature (5−40 °C), relative solute concentration in acetone (0.5−0.9), and stirring rate (150−1000 rpm) on product quality was investigated. The average particle size of the monoclinic paracetamol crystals was successfully controlled between 50 and 250 μm by changing the specific CO2 addition rate accordingly in a range spanning about 2 orders of magnitude. It was demonstrated that, in agreement with previous studies and theoretical investigations, the mean particle size decreases when the antisolvent addition rate is increased. Increasing the operating temperature led to an increase of the mean crystal size, while altering the concentration of the starting solution showed virtually no effect. As it would be expected, high stirrer speeds favored mechanical comminution, thus increasing the fines fraction in the recovered product. The results obtained in the experiments carried out in a 1-L precipitator are qualitatively and quantitatively in good agreement with those obtained in a 400-mL precipitator, thus once more underlining the robustness of GAS recrystallization. Residual solvent content in the dry product and yield were always within acceptable limits in both experimental facilities. The crystal habit obtained and the effect on it of the operating conditions are consistent with previous literature results.