Bioadhesive Matrix Microparticle Systems for Controlled Delivery of Fluoride

Objectives: Fluoride clearance following the use of dentifrice or rinse is rapid, yet even moderately elevated concentrations are believed to confer significant cariostatic benefits. The present aim was to manufacture chitosan/fluoride microparticles by spray drying, undertake physicochemical characterisation, and consider their utility for controlled release. Methods: Microparticles were manufactured from dispersions containing 1.0 and 2.0%w/v chitosan and 0.20 or 0.40%w/v NaF in the absence/presence of glutaraldehyde. Size distribution was determined using laser diffraction; fluoride loading/concentrations were determined by ion–selective electrode. Release profiles were determined in isotonic media at pH4.0, 5.5 and 7.0 over 360min. Particle morphology was investigated using environmental SEM. Bioadhesion parameters were determined using a texture-probe analyser, microparticle-based compressed discs, and porcine mucosae. Results: Microparticles exhibited low polydispersity and volume mean diameters (VMD) <6µm. VMDs increased on doubling the chitosan/fluoride concentrations but were largely independent of glutaraldehyde concentration. Recovered yields were inversely proportional to dispersion viscosity due to fluid atomisation effects; adding NaF reduced viscosity and improved yields. Best-case entrapment efficiency and NaF loading exceeded 84% and 14% respectively. Release profiles were biphasic with an initial burst releasing 40-60% of the total fluoride at the 600s timepoint, followed by a prolonged release phase extending out to 6h. Incorporation of 0.40% NaF to the 2.0% chitosan dispersion yielded microparticles whose compressed form exhibited markedly reduced bioadhesive parameters (Fmax and WOA) versus the chitosan-only control. Irrespective, chitosan/fluoride microparticles retained significant bioadhesive potential and we consider they have meaningful utility in a variety of oral care formats including anhydrous pastes, pressure-actuated aerosols and bioadhesive buccal discs Conclusion: Bioadhesive chitosan/fluoride microparticles manufactured using a low cost spray-drying protocol have been extensively characterised and further opportunity for optimisation identified. Their potential utility as controlled fluoride delivery vehicles in a variety of oral care formats is clear.