title: Mechanistic evaluation of factors affecting compound loading into ion-exchange fibers.
abstract: Donnan theory was applied to gain mechanistic understanding on the factors affecting drug loading process, compound-fiber affinity and subsequent release from fibrous ion-exchangers. Impact of initial loading solution concentration on fiber occupancy and loading efficiency of compounds were assessed experimentally and theoretically. Relative affinity towards the anion-exchange fibers was studied by dual loading of monovalent salicylic acid and either more lipophilic 3-isopropylsalicylic acid or divalent 5-hydroxyisophthalic acid. The effect of fiber framework on compound binding was evaluated separately for weakly and strongly basic fibers of similar ion-exchange capacities. The results revealed that loading into the ion-exchange fibers can be efficiently adjusted by the concentration of loading solution, leading to improved controllability of drug release from the fiber and minimised drug loss during the loading procedure. Ion-exchange fibers can be utilised successfully in simultaneous delivery of two ionic drugs, which offers a potential drug delivery system for synergistically active drugs. However, physicochemical characteristics of the drug (lipophilicity, valence) and framework of fibrous ion-exchanger affect the relative affinity of the drug towards the fiber, and should not be neglected when selecting appropriate ion-exchange fiber or optimising the external conditions during loading/release. Application of Donnan theory in modelling calculations supported precisely the experimental observations of compound loading (fiber occupancy and loading efficiency).
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. kaisa.hanninen@helsinki.fi
authors.forename: Kaisa
authors.initials: K
authors.lastname: Hänninen
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Kaukonen
authors.forename: Lasse
authors.initials: L
authors.lastname: Murtomäki
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
mesh_terms: D000465:Algorithms; D002118:Calcium / Q000737:chemistry; D002411:Cation Exchange Resins / Q000737:chemistry*; D002413:Cations, Divalent / Q000737:chemistry; D002414:Cations, Monovalent / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008274:Magnesium / Q000737:chemistry; D008962:Models, Theoretical; D015394:Molecular Structure; D010795:Phthalic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D012459:Salicylates / Q000737:chemistry / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: C523091:3-isopropylsalicylic acid; D002411:Cation Exchange Resins; D002413:Cations, Divalent; D002414:Cations, Monovalent; D010795:Phthalic Acids; D011726:Pyridinium Compounds; D012459:Salicylates; C037880:5-hydroxyisophthalic acid; D008274:Magnesium; D002118:Calcium