title: Evaluation of scale-up from analytical to preparative supercritical fluid chromatography.
abstract: An approach for reliable transfer from analytical to preparative scale supercritical fluid chromatography was evaluated. Here, we accounted for the conditions inside the columns as well as to the fact that most analytical instruments are volume-controlled while most preparative scale units are mass-controlled. The latter is a particular problem when performing pilot scale experiments and optimizations prior to scaling up to production scale. This was solved by measuring the mass flow, the pressure and the temperature on the analytical unit using external sensors. Thereafter, it was revealed with a design of experiments approach that the methanol fraction and the pressure are the two most important parameters to control for preserved retention throughout the scale-up; for preserved selectivity the temperature was most important in this particular system. Using this approach, the resulting chromatograms from the preparative unit agreed well with those from the analytical unit while keeping the same column length and particles size. A brief investigation on how the solute elution volume varies with the volumetric flow rate revealed a complex dependency on pressure, density and apparent methanol content. Since the methanol content is a parameter of great importance to control during the scale up, we must be careful when changing operational and column design conditions which generates deviations in pressure, density and methanol content between different columns.
authors.affiliation: Department of Engineering and Chemical Sciences, INTERACT, Karlstad University, SE-651 88 Karlstad, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Enmark
authors.affiliation: Department of Engineering and Chemical Sciences, INTERACT, Karlstad University, SE-651 88 Karlstad, Sweden.
authors.forename: Dennis
authors.initials: D
authors.lastname: Åsberg
authors.affiliation: Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, 431 83 Molndal, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Leek
authors.affiliation: Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, 431 83 Molndal, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Öhlén
authors.affiliation: Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, 431 83 Molndal, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Klarqvist
authors.affiliation: Department of Engineering and Chemical Sciences, INTERACT, Karlstad University, SE-651 88 Karlstad, Sweden. Electronic address: Jorgen.Samuelsson@kau.se.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Samuelsson
authors.affiliation: Department of Engineering and Chemical Sciences, INTERACT, Karlstad University, SE-651 88 Karlstad, Sweden. Electronic address: Torgny.Fornstedt@kau.se.
authors.forename: Torgny
authors.initials: T
authors.lastname: Fornstedt
mesh_terms: D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D000432:Methanol; D010316:Particle Size; D011312:Pressure; D012997:Solvents; D013696:Temperature
chemical_list: D012997:Solvents; D000432:Methanol
keywords: Chiral separation; Design of experiments; Operational parameters; SFC; Scale-up; Transfer of method