Characterization of the Subcritical Water Extraction of Fluoxetine-Hydrochloride

Abstract

The characteristics of using Subcritical Water Extraction (SWE) to recover Fluoxetine-Hydrochloride from both standard solutions and the contents of commercial capsule formulations were investigated. Analysis of solutions and extracts was done by HPLC with UV detection at 254 nm. Standard solutions of Fluoxetine-Hydrochloride were exposed to a variety of SWE operating conditions, including temperatures from 125 to 275°C and periods ranging from 5 to 30 min. Fluoxetine-Hydrochloride could be quantitatively recovered from standard solutions (1.0mg/mL) that were heated up to 175°C for 30 min, up to 200°C for 15 min, or up to 225°C for 10 min. At higher temperatures and/or times, Fluoxetine-Hydrochloride recoveries were generally incomplete and often produced decomposition by-products during the process. By comparison, the concentration of Fluoxetine-Hydrochloride in the standard solution had relatively little effect on recovery. Considering these parameters, an SWE method was developed to extract Fluoxetine-Hydrochloride from the contents of Prozac(®) capsules. It was found that Fluoxetine-Hydrochloride could be quantitatively extracted from the capsule contents in 8 min at a temperature of 200°C using 3.5 mL of water as the extraction solvent. Gelatinization of the starch excipient in the capsule contents was also observed to occur temporarily during the capsule extractions, before ultimately disappearing again. The period of this phenomenon was dependent on both temperature and sample size. The results indicate that SWE can be a very useful method for Fluoxetine-Hydrochloride extraction and suggest that it may be interesting to explore other pharmaceuticals using this method as well.