title: Purification of pharmaceutical excipients with supercritical fluid extraction.
abstract: Supercritical fluid extraction (SFE), with carbon dioxide as the solvent, was tested for its ability to remove common reactive impurities from several pharmaceutical excipient powders including starch, microcrystalline cellulose (MCC), hydroxypropylcellulose (HPC), polyethylene oxide (PEO), and polyvinylpyrrolidone (PVP). Extraction of the small molecule impurities, formic acid and formaldehyde, was conducted using SFE methods under conditions that did not result in visible physical changes to polymeric excipient powders. It could be shown that spiked, largely surface-bound, impurities could be removed effectively; however, SFE could only remove embedded impurities in the excipient particles after significant exposure times due to slow diffusion of the impurities to the particle surfaces. Attempts at hydrogen peroxide extraction were hindered by its low solubility in CO2, thereby effectively precluding SFE for removal of hydrogen peroxide from excipients. This work suggests that SFE will only be commercially useful for removal of low molecular weight impurities in polymeric excipients when migration of the impurities to the particle surfaces is sufficiently rapid for extraction to be completed in a reasonable time frame.
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ashraf-Khorassani
authors.forename: Larry T
authors.initials: LT
authors.lastname: Taylor
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Waterman
authors.forename: Padma
authors.initials: P
authors.lastname: Narayan
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Brannegan
authors.forename: George L
authors.initials: GL
authors.lastname: Reid
mesh_terms: D002245:Carbon Dioxide / Q000737:chemistry; D025924:Chromatography, Supercritical Fluid; D004340:Drug Contamination / Q000517:prevention & control*; D005079:Excipients / Q000737:chemistry* / Q000592:standards; D005557:Formaldehyde / Q000302:isolation & purification; D005561:Formates / Q000302:isolation & purification; D006861:Hydrogen Peroxide / Q000302:isolation & purification; D004364:Pharmaceutical Preparations / Q000592:standards*; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D005079:Excipients; D005561:Formates; D004364:Pharmaceutical Preparations; D012997:Solvents; C030544:formic acid; D002245:Carbon Dioxide; D005557:Formaldehyde; D006861:Hydrogen Peroxide