INFLUENCE OF MOLECULAR-WEIGHT AND FORMULATION PH ON THE PRECORNEAL CLEARANCE RATE OF HYALURONIC-ACID IN THE RABBIT EYE

Hyaluronic acid is a natural polymer which, due to its water retaining capability, binds to cell membranes and can therefore be considered a s a putative vehicle for controlled ocular delivery. In an in vitro mu coadhesion test, the force of detachment was significantly greater for Healon(R) (HA-Na) compared to low molecular weight hyaluronic acid. A lso, this bioadhesion was stronger for Healon(R) at pH 5 than at pH 7. 4. The precorneal clearance of sodium hyaluronate (0.2%) was investiga ted at pH 5.0 and 7.4 by employing gamma scintigraphic imaging of the In-111-labelled biopolymer. Protonation of the macromolecule did not r esult in any increase in ocular mucoadhesion as the mean residence tim e at pH 5.0 was not significantly longer than at pH 7.4. The effect of molecular weight of hyaluronic acid on the corneal retention was also investigated. There was a statistically significant difference (p < 0 .05) in the clearance half-life (t(0.5)) and AUC of % activity remaini ng vs time plot for Healon(R) (Mol. Wt 2.2 x 10(6)) compared to those observed for the two lower molecular weight hyaluronic acid samples (M el. Wt 134 000 and 620 000).