In situ measurement of fluorescein release by collagen shields in human eyes

Fluorescein (F) and FITC Dextran (FD; MW 4400) have been used as inert analogs of active drugs to examine the factors controlling the rate of loss of drugs from collagen shields in vivo. The diffusion constants in the shield (120 microns thick) determined from in vitro release experiments were found to be 0.42 x 10(-6) for F and 0.16 x 10(-6) cm2/sec for FD at 34 degrees C and these values correspond to 0.7 and 0.27 min-1 rates of loss for the exponential parts of their release. In the eyes of 6 subjects, the F loaded shields lost the dye at an average rate of 0.016 min-1 initially, increasing to 0.026 min-1 at the end of an hour. Somewhat higher values were noted with FD and were attributed to variations of manufacturing of the shields. Comparing the rates of loss in in vitro and in vivo, it is clear that the latter is not controlled by the rate of diffusion in the shield, but is limited by the rates of tear secretion and flow over the surfaces of the shield. The penetration of F into the anterior chamber from a series of four drops applied 12 min apart was compared with that from a shield soaked in the drop solution to determine the enhancement in the bioavailability. This showed that the shield increased the penetration into the eye by about 16 times over that from a single drop. However, the rate of loss of F from the shield in vivo is only about 8 times slower than that from a drop instilled in the eye.(ABSTRACT TRUNCATED AT 250 WORDS)