title: Evaluation of Cetylpyridinium Chloride-Containing Mouthwashes Using In Vitro Disk Retention and Ex Vivo Plaque Glycolysis Methods.
abstract: The Disk Retention Assay (DRA) is an in vitro method developed to measure the available level of cetylpyridinium chloride (CPC) in mouthwash formulations. This method is based on the binding of the cationic CPC molecule to the anionic surface of a cellulose filter disk. Aqueous CPC solutions demonstrate a linear response (A545) for concentrations up to 0.3%. Higher levels of CPC showed no increased response in the assay. Among common oral product ingredients, at relevant concentrations, surfactants are the primary compounds which inhibit CPC detection and hence, chemical availability. Poloxamer-407 decreased CPC availability to 60% at 0.1%, to 10% at 0.5%, and to 24-33% for 0.2-0.4%. Polysorbate-80 decreased CPC availability to 30% at 0.1% and 6% at 0.25%. A range (4-54%) of available levels of CPC were determined for several commercial products containing 0.045-0.05% nominal levels of CPC indicating significant formulation excipient influence. A plaque glycolysis (PG) assay was used to determine the biological activity of all mouthwash products analyzed by DRA. An experimental series of mouthwash formulations having nominal CPC levels of 0-0.10% demonstrated a good correlation (r2 = 0.955) between the calculated available level of CPC (DRA) and inhibition of plaque glycolysis. The calculated available level of CPC from select commercial mouthwash products, also fit the established correlation with biological activity. The combination of DRA and plaque glycolysis methods are valuable tools which can be used during development to maximize the biological activity of CPC mouthwash formulations prior to clinical evaluation.
authors.affiliation: The Procter and Gamble Co, Mason, Ohio, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hunter-Rinderle
authors.forename: L A
authors.initials: LA
authors.lastname: Bacca
authors.forename: K T
authors.initials: KT
authors.lastname: McLaughlin
authors.forename: D
authors.initials: D
authors.lastname: Macksood
authors.forename: A C
authors.initials: AC
authors.lastname: Lanzalaco
authors.forename: J
authors.initials: J
authors.lastname: Parran
authors.forename: M J
authors.initials: MJ
authors.lastname: Doyle
mesh_terms: D065966:Absorption, Physicochemical; D000891:Anti-Infective Agents, Local / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry; D002594:Cetylpyridinium / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D003773:Dental Plaque / Q000378:metabolism*; D005374:Filtration / Q000295:instrumentation; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D008422:Materials Testing; D009067:Mouthwashes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D020442:Poloxamer / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000891:Anti-Infective Agents, Local; D009067:Mouthwashes; D011136:Polysorbates; D013501:Surface-Active Agents; D020442:Poloxamer; D002482:Cellulose; D002594:Cetylpyridinium