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.

The device with its continuous high-concentration delivery is promising for noninvasive delivery of surfactant aerosol to neonates and has the potential for becoming a versatile disperser platform closing the gap between continuously operating nebulizers and discontinuously operating dry powder inhaler devices.

Although not suitable for accurately predicting permeation the models may be suitable for determining a rank order of permeation, which may help to select candidate molecules for in-vitro screening. However, it is important to note that such predictions need to take into account actual relative drug candidate potencies.

In this study sucrose laurate was formulated in hydrogels and investigated as a suitable transdermal penetration enhancer for oestradiol. Using rabbits as an animal model, the absolute bioavailability and the skin irritation were evaluated after single and multiple application. Three hydrogels containing 60 mg% oestradiol were evaluated: Oestrogel, and two hypromellose gels containing 5 and 15% sucrose laurate (w/w), respectively. No stability problem of the sucrose laurate was detected during a storage period of four months at 7 +/- 2 degrees C. After single application no significant difference (P < 0.05) was observed between the bioavailability parameters of Oestrogel and the 5% sucrose laurate gel. The values obtained for the 15% sucrose laurate gel were significantly higher than for the other gels. When applied on day 7 after a 6-day treatment, twice daily with the respective placebo gel, no significant difference was seen amongst the three formulations for any of the parameters evaluated. When the results after multiple application were compared with those after single application, a significant increase in oestradiol bioavailability was seen for the gel containing 30% ethanol and a significant decrease in oestradiol bioavailability was seen for the 5 and 15% sucrose laurate gels. Histological evaluation of the untreated and treated skin biopsies, showed a significantly higher incidence of infiltrate for all treated skin biopsies in comparison with the untreated ones. A significant increase in skinfold thickness was seen for the skin biopsies treated with gel containing 15% sucrose laurate. It can be concluded that sucrose laurate shows a potential as an absorption enhancer for percutaneous drug delivery.

The in-vitro and in-vivo fluoride release of bioadhesive, slow-release tablets prepared from a mixture of polyethylene glycol polymers, containing 0.1 mg of fluoride as NaF was studied, and their ability to sustain fluoride levels in saliva were compared with conventional fluoride tablets with the same fluoride content. In-vitro release experiments showed that the bioadhesive tablets needed 8 h to release all their fluoride compared with less than 1 h for the conventional fluoride tablets. In-vivo, the bioadhesive tablets had a retention period of 6 h and could sustain a salivary fluoride level of more than 10 microM above the baseline for 7 h. The conventional fluoride tablets achieved a peak concentration of 0.5 mM directly after dissolution in the mouth, but the fluoride level could not be sustained for longer than 1 h. A good agreement was found between the in-vitro swelling behaviour of the bioadhesive tablets and their in-vitro and in-vivo release characteristics and their in-vivo retention time.