title: Crystallization using reverse micelles and water-in-oil microemulsion systems: the highly selective tool for the purification of organic compounds from complex mixtures.
abstract: The active pharmaceutical ingredient orlistat is usually manufactured using a semi-synthetic procedure, producing crude product and complex mixtures of highly related impurities with minimal side-chain structure variability. It is therefore crucial for the overall success of industrial/pharmaceutical application to develop an effective purification process. In this communication, we present the newly developed water-in-oil reversed micelles and microemulsion system-based crystallization process. Physiochemical properties of the presented crystallization media were varied through surfactants and water composition, and the impact on efficiency was measured through final variation of these two parameters. Using precisely defined properties of the dispersed water phase in crystallization media, a highly efficient separation process in terms of selectivity and yield was developed. Small-angle X-ray scattering, high-performance liquid chromatography, mass spectrometry, and scanning electron microscopy were used to monitor and analyze the separation processes and orlistat products obtained. Typical process characteristics, especially selectivity and yield in regard to reference examples, were compared and discussed.
authors.affiliation: Farma GRS, d.o.o., Novo Mesto 8000, Slovenia. alen.kljajic@krka.si
authors.forename: Alen
authors.initials: A
authors.lastname: Kljajic
authors.forename: Marija
authors.initials: M
authors.lastname: Bester-Rogac
authors.forename: Andrej
authors.initials: A
authors.lastname: Klobcar
authors.forename: Rok
authors.initials: R
authors.lastname: Zupet
authors.forename: Stane
authors.initials: S
authors.lastname: Pejovnik
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003460:Crystallization; D004655:Emulsions; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification*; D008823:Micelles; D009821:Oils / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry / Q000302:isolation & purification; D000077403:Orlistat; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004655:Emulsions; D007783:Lactones; D008823:Micelles; D009821:Oils; D009930:Organic Chemicals; D014867:Water; D000077403:Orlistat