Development and testing of bioadhesive, fluoride-containing slow-release tablets for oral use

The bioadhesive characteristics of tablets for oral use made from modified starch, polyacrylic acid (PAA), polyethylene glycol (PEG) and sodium carboxymethylcellulose (CMC) were investigated. Adhesion force and energy were determined in-vitro and maximal adhesion time was evaluated in-vivo in human subjects. In-vitro, PAA showed the best bioadhesive properties, followed by modified maize starch and PEG with a mol. wt of 300,000-400,000 daltons. The presence of 0.1 mg of fluoride as NaF did not lead to significant differences in adhesion force and energy for the same formulation. The in-vivo bioadhesion was not strongly correlated to the in-vitro data. PAA, despite its excellent adhesion, proved to be irritating to the mucosa. PEG with a mol, wt of 200,000 daltons was subject to erosion. CMC showed good bioadhesive properties but the mechanical strength of the tablets was low. Modified maize starch tablets containing 5% (w/w) PAA and PEG with a mol. wt of 300,000 daltons proved to be the most suitable formulations for a fluoride-slow-release tablet with bioadhesive properties. In-vitro, the tablets released all of the fluoride within the 8 h period, with a high initial release. The release rate was related to the water absorption rate of the tablets. The PAA-containing formulations and the CMC formulations had the fastest release. In-vivo, fluoride levels with a minimum of 150 and a maximum of 1000 micrograms mL-1 were maintained for 8 h in the oral cavity. These fluoride levels were sustained significantly longer than those obtained with the administration of fourfold the amount of fluoride in the form of a fluoride-containing toothpaste. The release characteristics in-vivo exhibited a high variation. The use of bioadhesive polymers in oral pharmacotherapy seems promising.