title: Predicting critical micelle concentration and micelle molecular weight of polysorbate 80 using compendial methods.
abstract: This manuscript addresses the capability of compendial methods in controlling polysorbate 80 (PS80) functionality. Based on the analysis of sixteen batches, functionality related characteristics (FRC) including critical micelle concentration (CMC), cloud point, hydrophilic-lipophilic balance (HLB) value and micelle molecular weight were correlated to chemical composition including fatty acids before and after hydrolysis, content of non-esterified polyethylene glycols and sorbitan polyethoxylates, sorbitan- and isosorbide polyethoxylate fatty acid mono- and diesters, polyoxyethylene diesters, and peroxide values. Batches from some suppliers had a high variability in functionality related characteristic (FRC), questioning the ability of the current monograph in controlling these. Interestingly, the combined use of the input parameters oleic acid content and peroxide value - both of which being monographed methods - resulted in a model adequately predicting CMC. Confining the batches to those complying with specifications for peroxide value proved oleic acid content alone as being predictive for CMC. Similarly, a four parameter model based on chemical analyses alone was instrumental in predicting the molecular weight of PS80 micelles. Improved models based on analytical outcome from fingerprint analyses are also presented. A road map controlling PS80 batches with respect to FRC and based on chemical analyses alone is provided for the formulator.
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Braun
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Ilko
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Merget
authors.affiliation: GILYOS GmbH, Wuerzburg, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Gieseler
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Germershaus
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg, Germany. Electronic address: l.meinel@pharmazie.uni-wuerzburg.de.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005079:Excipients / Q000032:analysis / Q000737:chemistry* / Q000592:standards; D005227:Fatty Acids / Q000032:analysis; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D008823:Micelles; D008956:Models, Chemical; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000032:analysis; D011136:Polysorbates / Q000032:analysis / Q000737:chemistry* / Q000592:standards; D012542:Scattering, Radiation; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D005227:Fatty Acids; D008823:Micelles; D011136:Polysorbates; D011092:Polyethylene Glycols
keywords: Cloud point; Critical micelle concentration; Fatty acid composition; Hydrophilic–lipophilic balance; Micelle molecular weight; Peroxide value; Polysorbate 80