title: Development of an ex vivo retention model simulating bioadhesion in the oral cavity using human saliva and physiologically relevant irrigation media.
abstract: In recent years, there has been a particular interest in bioadhesive formulations for oromucosal drug delivery as this may promote prolonged local therapy and enhanced systemic effect. Saliva plays a vital role in oromucosal drug absorption by dissolving the drug and presenting it to the mucosal surface. However, the rheological, chemical, and interfacial properties of this complex biological fluid may strongly affect the adhesion of bioadhesive formulations. There is a need for well characterized in vitro models to assess the bioadhesive properties of oral dosage forms for administration in the oral cavity. Thus we aimed at developing an advanced ex vivo buccal retention model, with focus on choosing a physiologically relevant irrigation media closely resembling human saliva. Spray dried chitosan microparticles containing metformin hydrochloride as an example of a small hydrophilic drug, were employed as bioadhesive formulations. Chewing-stimulated human whole saliva was collected and characterized for use in retention studies in comparison with four artificial irrigation media; phosphate buffer, Saliva Orthana(®), porcine gastric mucin base media (PGM3), and xanthan gum based media (XG2). Retention of metformin, applied as spray dried microparticles on porcine buccal mucosa, greatly depended on the characteristics of the irrigation media. When rheology of the irrigation media was examined, changes in retention profiles could be interpreted, as irrigation media containing mucin and xanthan gum possessed a higher viscosity than phosphate buffer, which led to longer retention of the drug due to better hydration of the mucosa and the spray dried microparticles. Metformin retention profiles were comparable when human saliva, Saliva Orthana(®), or PGM3 were used as irrigation media. Moreover, PGM3 displayed physico-chemical properties closest to those of human saliva with regard to pH, protein content and surface tension. Saliva Orthana(®) and PGM3 are therefore considered as suitable irrigation media for further retention studies.
authors.affiliation: Section for Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Katrine D
authors.initials: KD
authors.lastname: Madsen
authors.forename: Camilla
authors.initials: C
authors.lastname: Sander
authors.forename: Stefania
authors.initials: S
authors.lastname: Baldursdottir
authors.forename: Anne Marie L
authors.initials: AM
authors.lastname: Pedersen
authors.forename: Jette
authors.initials: J
authors.lastname: Jacobsen
mesh_terms: D000268:Adhesiveness; D000278:Administration, Buccal; D000328:Adult; D000818:Animals; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008863:Microspheres; D009061:Mouth Mucosa / Q000378:metabolism*; D012212:Rheology; D012463:Saliva / Q000737:chemistry / Q000378:metabolism*; D013045:Species Specificity; D013500:Surface Tension; D013552:Swine; D055815:Young Adult
chemical_list: D004337:Drug Carriers; D007004:Hypoglycemic Agents; D048271:Chitosan; D008687:Metformin