BIOADHESION - THE EFFECT OF POLYACRYLIC-ACID ON THE OCULAR BIOAVAILABILITY OF TIMOLOL

The bioadhesive polymer, polyacrylic acid, was added to ophthalmic formulations and the effect on the ocular distribution of timolol evaluated. Ocular bioavailability of 0.5% Timoptol(R) was measured in cornea, aqueous humor and iris + ciliary body, of albino rabbits and was compared to that of 0.5% timolol in isoviscous solutions of polyvinyl alcohol (PVA), polyacrylic acid (PAA) and timolol-polyacrylic acid salt (PAA salt). Ocular bioavailability of timolol was increased by each of the viscous solutions. These increases, assessed by measurement of AUC (0-4 h) in cornea, aqueous humor and iris + ciliary body ranged from 1.4- to 2.8-fold. The largest increases were obtained with the non-mucoadhesive polymer, PVA. The bioadhesive PAA polymers modified the concentration vs time profiles of timolol and gave the highest timolol concentrations in iris + ciliary body at later sampling times.