Enhanced Fluidity Liquid Extraction (EFLE) using carbon dioxide–methanol mixtures as the mobile phase is explored for its ability to extract Fluoxetine-Hydrochloride, the active pharmaceutical ingredient in Prozac® capsules. Optimum conditions for extracting the pure compound were found using a 50% carbon dioxide–50% methanol mobile phase. Co-extraction and/or interference from common excipients such as starch, lactose, and micro-crystalline cellulose was not observed. However, mannitol excipient was found to significantly reduce the EFLE extraction efficiency of Fluoxetine-Hydrochloride. Employing an extraction temperature of 80 °C, a pressure of 375 atm, and a flow rate of 3.5 mL min−1, produced an extraction recovery of Fluoxetine-Hydrochloride from Prozac® capsules of 99 ± 2% in just 3 minutes using only about 5 mL of total methanol. When a static modifier mode was employed under similar conditions, it was found that only 400 μL of methanol added to the vessel prior to extraction with pure carbon dioxide resulted in a Fluoxetine-Hydrochloride recovery of 98 ± 8% after only 5 minutes. In contrast to EFLE results, Fluoxetine-Hydrochloride extractions performed using pure room temperature methanol were 3 to 5 times longer and produced extracts that contained significant amounts of starch excipient that was also co-extracted from the Prozac® capsules. These findings indicate that EFLE may be a useful alternative sample preparation method for Fluoxetine-Hydrochloride, and possibly other pharmaceuticals, that can greatly reduce time and solvent usage in the process.
