Enhancement of the Mydriatic Response to Tropicamide by Bioadhesive Polymers

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Abstract
The aim of this work was to evaluate how the addition of mucoadhesive polymers 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 polyacrylic acid (PAA; 0.2%; w/v). Polymeric solutions were compared to a nonviscous 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% and 87.6% for formulations with CMC, PAA, HA and AS, respectively. The mydriatic response of tropicamide was determined in adult male New Zealand rabbits, weighing 1.7-2 Kg, by pupil diameter measurements at different times after instillation. The area under the mydriatic response-time curve (AUC 0-6 hr) was interpreted as an indication of the bioavailability of tropicamide in each vehicle. The AUC 0-6 hr was related to the in vitro mucoadhesion for each formulation. Tropicamide solutions with CMC-Na and PAA resulted 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 than 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 to that observed in the lacrimal fluid, with the Imax (maximum pupil diameter) 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 value of muco-adhesion similar to the reference mucin-mucin.