Semisolid ophthalmic vehicles. III. An evaluation of four organic hydrogels containing pilocarpine

Abstract

The validity of four hydrogels, based on synthetic polymers as vehicles for topical ophthalmic drugs was evaluated by determining, in rabbits and in humans, the miotic response induced by pilocarpine. The hydrogels were prepared with two different types of poly(acrylic acid), PAA-1 and PAA-2; with poly(acrylamide) PAAm and with ethylene maleic anhydride, EMA. Their biological effect was compared with that induced by an aqueous solution of the drug (AS). The rheological characteristics of the vehicles were investigated: PAA-1, PAA-2 and EMA displayed a plastic type of flow, while PAAm was pseudo-plastic. In rabbits administration of pilocarpine in the hydrogel vehicles doubled the drug bioavailability (as expressed by the area under the miotic response vs time curve, AUC) with respect to AS; however, no statistical differences were apparent among the AUC values of the hydrogels. In humans, the same vehicles showed more pronounced activity differences. While PAA-2 and PAAm produced an approximately 3-fold bioavailability increase with respect to AS, PAA-1 only doubled the bioavailability and EMA showed activity parameters not different from those of the aqueous solution. Possible correlations between the viscosity parameters of the vehicles and ophthalmic bioavailability in the two species are discussed. The present results appear to confirm previous observations on the poor validity of rabbits for studies on the influence of vehicle viscosity on bioavailability of topical ophthalmic drugs.