title: Ketoprofen enantioseparation with a Cinchona alkaloid based stationary phase: enantiorecognition mechanism and release studies.
abstract: With the present contribution, we demonstrate that the baseline separation of ketoprofen enantiomers can be successfully achieved (α = 1.09; R(S) = 1.60) in the reversed-phase mode of elution with a commercially available anion-exchange-based chiral stationary phase, incorporating the quinine 2,6-diisopropylphenyl carbamate derivative as the enantioresolving unit. Focused modification of the eluent composition indicated a stereoselective role of hydrophobic and π-π interactions between the selector and selectand units, besides the prime ionic intermolecular interaction. The mechanistic hypotheses based on the chromatographic data were confirmed by in silico molecular dynamic simulations, which allowed us to establish the network of selector-selectand interactions underlying the stereorecognition process at a molecular level. The validated method was successfully used to evaluate the drug content and release profile of ketoprofen-loaded polymeric film, showing drug homogeneous distribution into the film and no preferential interactions between the polymer and one of the enantiomers, with the racemate released at each time point.
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Roccaldo
authors.initials: R
authors.lastname: Sardella
authors.forename: Antonella
authors.initials: A
authors.lastname: Lisanti
authors.forename: Andrea
authors.initials: A
authors.lastname: Carotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Blasi
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lindner
authors.forename: Benedetto
authors.initials: B
authors.lastname: Natalini
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D002930:Cinchona Alkaloids / Q000737:chemistry*; D007660:Ketoprofen / Q000737:chemistry* / Q000302:isolation & purification*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D002930:Cinchona Alkaloids; D007660:Ketoprofen
keywords: Drug delivery; Enantiorecognition; Ion-exchange chromatography; Poly(d,l-lactide-co-glycolide); Quinine-based stationary phases