| Continuous secretion of tears, frequent blinking and a surface epithelium with low permeability are the main factors protecting the eye against external factors. Obviously, this protective barrier also reduces the efficacy of ocular drugs applied topically.; The suitability of polymer preparations (both liquid and solid dosage forms) to lengthen the precorneal residence time of the drug and to increase the ocular bioavailability, by interacting with the lachrymal mucus layer, is evaluated in the present study. The clarification of the mucoadhesive interaction mechanism(s) is accomplished by the development of an in vitro technique using oscillatory shear rheology. Implementation of several rheological procedures enables the characterisation of the degree and type of network formation between the polymer and mucin. The results obtained with the in vitro technique are verified in vivo by ocular fluorophotometry determining the ocular elimination kinetics.; The capability of ocular liquid dosage forms to interact significantly with a mucus layer and to modify the ocular kinetics seems to be very limited. The only alternative to realize ocular mucoadhesion is to apply dry dosage forms, attaching to the mucus layer by dehydrating it instead of interpenetrating it, as is observed in the case of liquid dispersions. Formation of mucoadhesive bonds is confirmed after mixing mucin and a dry polyacrylic acid derivative. In vivo results further demonstrate that the dry dosage form, in contradiction to the liquid dispersion, actually lengthens the precorneal residence time and increases the bioavailability of a fluorescent tracer. According to the acceptability data, the tablet is well-tolerated after application to humans.; General conclusion is that to influence significantly the precorneal residence time and the ocular bioavailability, the use of a mucoadhesive minitablet seems to be inevitable. Liquid polymer dispersions can also interact with mucin, but the interaction mechanisms as demonstrated by the in vitro experiments are insufficient to achieve a significant in vivo effect. |
