Effect of particle dissolution rate on ocular drug bioavailability.

Aqueous ophthalmic drug solutions typically exhibit low bioavailability due to various loss processes such as drainage, tear turnover, nonproductive absorption, and protein binding. Suspensions may improve bioavailability, but because of a short residence time and a low corneal permeability rate constant, the dissolution rate of the drug and its intrinsic solubility must be considered. The relationship between the various parameters affecting the relative dissolution rate have not heretofore been examined with respect to the eye. In the present study, a kinetic model that predicts ocular tissue drug levels for suspensions has been developed and tested using a steroid, fluorometholone, as the test drug suspension. The proposed model is able to predict the effects of particle size, concentration, and changes in drainage rate such that a reasonable a priori prediction of drug levels can be made.