title: Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions.
abstract: Cyclodextrins (CDs) are enabling pharmaceutical excipients that can be found in numerous pharmaceutical products worldwide. Because of their favorable toxicologic profiles, CDs are often used in toxicologic and phase I assessments of new drug candidates. However, at relatively high concentrations, CDs can spontaneously self-assemble to form visible microparticles in aqueous mediums and formation of such visible particles may cause product rejections. Formation of subvisible CD aggregates are also known to affect analytical results during product development. How and why these CD aggregates form is largely unknown, and factors contributing to their formation are still not elucidated. The physiochemical properties of CDs are very different from simple amphiphiles and lipophilic molecules that are known to self-assemble and form aggregates in aqueous solutions but very similar to those of linear oligosaccharides. In general, negligible amounts of aggregates are formed in pure CD solutions, but the aggregate formation is greatly enhanced on inclusion complex formation, and the extent of aggregation increases with increasing CD concentration. The diameter of the aggregates formed is frequently less than about 300 nm, but visible aggregates can also be formed under certain conditions.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Alexey
authors.initials: A
authors.lastname: Ryzhakov
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition, Katholieke Univ Leuven, Leuven, Belgium.
authors.forename: Thao
authors.initials: T
authors.lastname: Do Thi
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition, Katholieke Univ Leuven, Leuven, Belgium.
authors.forename: Jef
authors.initials: J
authors.lastname: Stappaerts
authors.affiliation: Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Bertoletti
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Kimpe
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: André Rodrigues
authors.initials: AR
authors.lastname: Sá Couto
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Phennapha
authors.initials: P
authors.lastname: Saokham
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition, Katholieke Univ Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition, Katholieke Univ Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Govert W
authors.initials: GW
authors.lastname: Somsen
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland; Alvotech Iceland, Reykjavik, Iceland.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kurkov
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Inghelbrecht
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: Albertina
authors.initials: A
authors.lastname: Arien
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: M Ilias
authors.initials: MI
authors.lastname: Jimidar
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Schrijnemakers
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland. Electronic address: thorstlo@hi.is.
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
mesh_terms: D003505:Cyclodextrins / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D006860:Hydrogen Bonding; D008823:Micelles; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000592:standards; D012996:Solutions; D014783:Viscosity; D014867:Water / Q000737:chemistry*
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D008823:Micelles; D004364:Pharmaceutical Preparations; D012996:Solutions; D014867:Water
keywords: aggregates; complexation; cyclodextrin; inclusion compounds