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 as a putative vehicle for controlled ocular delivery. In an in vitro mucoadhesion test, the force of detachment was significantly greater for Healon® (HA-Na) compared to low molecular weight hyaluronic acid. Also, this bioadhesion was stronger for Healon® at pH 5 than at pH 7.4. The precorneal clearance of sodium hyaluronate (0.2%) was investigated at pH 5.0 and 7.4 by employing gamma scintigraphic imaging of the 111 In-labelled biopolymer. Protonation of the macromolecule did not result in any increase in ocular mucoadhesion as the mean residence time 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 (t0.5) and AUC of % activity remaining vs time plot for Healon® (Mol. Wt 2.2 × 106) compared to those observed for the two lower molecular weight hyaluronic acid samples (Mol. Wt 134 000 and 620 000).