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

• Beclometasone dipropionate and Budesonide were purified by supercritical CO 2. • The optimal conditions for solvent residue extraction were 200 bar, 40 °C, and 0.7 kg/h CO 2 flow rate. • Total organic solvent residues of 11,100 ppm and 41,000 ppm were reduced to 5 ppm and 52 ppm, respectively. • Final solvent residues largely lower than those obtainable using multi-step traditional processes. [Display omitted] 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 CO 2. The process was carried out at pressures from 80 to 370 bar, CO 2 flow rates between 0.1 and 1.0 kg/h, and at a temperature of 40 °C. When CO 2 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 CO 2 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 CO 2 flow rate: total final solvent residues of 5 ppm and 52 ppm for Beclo and Bude, respectively, were reached. [ABSTRACT FROM AUTHOR]