Supercritical CO2 elimination of solvent residues from active pharmaceutical ingredients: Beclometasone dipropionate and Budesonide

Abstract

The scope of this work was to reduce/eliminate Class 2 and Class 3 solvents, contained in two active pharmaceutical ingredients (APIs), Beclometasone dipropionate (Beclo) and Budesonide (Bude), using supercritical CO2. The process was carried out at pressures from 80 to 370 bar, CO2 flow rates between 0.1 and 1.0 kg/h, and at a temperature of 40 °C. When CO2 density was too low (e.g., at 80 bar and 40 °C), an incomplete extraction of the solvents was obtained. When the extraction pressure was too large (e.g., 370 bar), also a non-negligible co-extraction of solid material was observed. Particles bed caking emerged at CO2 flow rates larger than 0.7 kg/h. The optimal process conditions were found operating at 200 bar and 40 °C, using a 0.7 kg/h CO2 flow rate: total final solvent residues of 5 ppm and 52 ppm for Beclo and Bude, respectively, were reached.