Development of an ex vivo retention model simulating bioadhesion in the oral cavity using human saliva and physiologically relevant irrigation media

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 sur...

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Bibliographic Details
Published in:International journal of pharmaceutics 2013-05, Vol.448 (2), p.373-381
Main Authors: Madsen, Katrine D., Sander, Camilla, Baldursdottir, Stefania, Pedersen, Anne Marie L., Jacobsen, Jette
Format: Article
Language:English
Subjects:
adhesion
Adhesiveness
Administration, Buccal
Adult
Animals
Bioadhesion
Buccal
chitosan
Chitosan - chemistry
Drug Carriers - chemistry
Drug Compounding
Drug Delivery Systems
drug formulations
Female
Humans
Hydrogen-Ion Concentration
hydrophilicity
Hydrophobic and Hydrophilic Interactions
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacokinetics
irrigation
Male
metformin
Metformin - administration & dosage
Metformin - chemistry
Metformin - pharmacokinetics
Metformin hydrochloride
Microspheres
mouth
Mouth Mucosa - metabolism
mucins
mucosa
oral administration
pharmacokinetics
protein content
Retention model
Rheology
saliva
Saliva - chemistry
Saliva - metabolism
Saliva substitute
simulation models
Species Specificity
spray drying
Surface Tension
Swine
therapeutics
viscosity
Whole saliva
xanthan gum
Young Adult
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Summary: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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2013.03.031