Enhancement of the mydriatic response to tropicamide by bioadhesive polymers

The aim of this work was to evaluate how the addition of mucoadhesive polym ers to aqueous solutions affects the ocular response of tropicamide (0.2%; w/v). The polymer solutions tested were carboxymethylcellulose sodium salt( CMC-Na; 1%; w/v), hyaluronic acid sodium salt (HA-Na; 0.1%; w/v) and polyac rylic acid (PAA; 0.2%; w/v). Polymeric solutions were compared to a nonvisc ous formulation(AS). In vitro mucoadhesion measurements were expressed as a percentage of the adhesion force mucin-mucin, considering this one as 100% mucoadhesion. The values of mucoadhesion obtained were 172%, 127%, 103% an d 87.6% for formulations with CMC, PAA, HA and AS, respectively. The mydriatic response of tropicamide was determined in adult male New Zeal and rabbits, weighing 1.7-2 Kg, by pupil diameter measurements at different times after instillation. The area under the mydriatic response-time curve (AUC(0-6hr)) was interpreted as an indication of the bioavailability of tr opicamide in each vehicle. The AUC(0-6hr) was related to the in vitro mucoa dhesion for each formulation. Tropicamide solutions with CMC-Na and PAA res ulted in mucoadhesion and AUC(0-6hr) values approximately 1.9 and 1.4 times higher than AS. Although the solution with HA-Na was less mucoadhesive tha n PAA, the hyaluronic acid solution resulted in a higher AUC mydriasis/time value. Formulations with HA-Na and PAA presented values of surface tension close t o that observed in the lacrimal fluid, with the I-max (maximum pupil diamet er) being higher than for CMC-Na and AS. Greater than 90% of the mydriatic effect disappeared 4.5 hr after instillation for PAA and AS. Nevertheless, the mydriatic effect remained up to 5.5 hr for HA-Na and CMC-Na. HA-Na solution enhanced the bioavailability of tropicamide, presenting a va lue of mucoadhesion similar to the reference mucin-mucin.