title: Development of supercritical fluid extraction and supercritical fluid chromatography purification methods using rapid solubility screening with multiple solubility chambers.
abstract: Rapid solubility screening in diverse supercritical fluids (SCFs) was carried out via multiple solubility chambers with a trapping device and online ultraviolet (UV) detection. With this device, it was possible to rapidly study the solubility variations of multiple components in a mixture. Results from solubility studies have been used to develop efficient supercritical fluid extraction (SFE) and supercritical fluid chromatography (SFC) methods. After the investigation of solubilities of theophylline and caffeine in several neat organic solvents and SCFs, advantages of SFE over conventional organic solvent extraction were demonstrated with a model mixture of theophylline and caffeine. The highest solubility ratio of 1:40 (theophylline:caffeine) was observed in the SCF with 20% acetonitrile (MeCN), where a ratio of 1:11 was the highest in the neat organic solvents. A model mixture of theophylline:caffeine (85:15 w/w, caffeine as an impurity) was successfully purified by SFE by leveraging the highest solubility difference. The SCF with 20% MeCN selectively removed caffeine and left theophylline largely intact. Rapid SCF solubility screening was applied to development of SFE and SFC methods in a drug discovery environment. Two successful applications were demonstrated with proprietary Amgen compounds to either remove an achiral impurity before chiral purification or enhance chiral chromatographic throughput.
authors.affiliation: Discovery Analytical Sciences, CR&D, Amgen, Inc, Thousand Oaks, California, USA. kgahm@amgen.com
authors.forename: Kyung H
authors.initials: KH
authors.lastname: Gahm
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.forename: Wesley W
authors.initials: WW
authors.lastname: Barnhart
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Goetzinger
mesh_terms: D002110:Caffeine / Q000737:chemistry; D002621:Chemistry / Q000379:methods; D002845:Chromatography / Q000379:methods*; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D006860:Hydrogen Bonding; D000432:Methanol / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification; D011312:Pressure; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature; D013806:Theophylline / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D002110:Caffeine; D013806:Theophylline; D000432:Methanol