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Paracetamol was precipitated from solution in acetone using compressed carbon dioxide (CO 2 ) 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 CO 2 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.

Experimental data are reported on particle size distributions of paracetamol precipitated from an acetone solution using compressed CO2 as an antisolvent. When the solution is sprayed into dense CO2 using the “precipitation with compressed antisolvents” (PCA) process (in two different PCA units), the average particle size is approximately 2 μm in the 83−120 bar, 33−62 °C, 70−138 g/min of CO2 range. When the operating pressure and temperature are below or close to the critical locus for the CO2 + acetone binary, the particles tend to be spherical and agglomerated, presumably because the surface roughening temperature was exceeded. Well above the critical locus, the particles are less aggregated with distinguishable crystal faces. In contrast, bubbling compressed CO2 through the paracetamol solution (the so-called GAS process) yielded 90−250 μm particles at 25 °C in the 5−50 g/min of CO2 range. Through the definition of characteristic mass-transfer times (τmt) for the PCA and GAS processes based on published mathematical models, it is shown that the 2 orders of magnitude disparity in the average particle size is mirrored by a similar disparity in the τmt values for the two processes. These results suggest that the PCA and GAS processes, with common underlying mass-transfer mechanisms, may be essentially viewed in a continuum of characteristic mass-transfer time scales, with the higher τmt values yielding progressively larger particles. This result may be useful to rationally interpret and manipulate particle sizes in these processes.