Preparation and Evaluation of A Sustained-Release Ophthalmic Vehicle for Dapiprazole

Abstract

The present investigation is concerned with the development and “in vivo” evaluation of a long-acting ocular vehicle for the α-adrenergic blocking drug dapiprazole (DAP). The approaches tested for prolonging the activity were a) salification of the drug base with polygalacturonic acid (PGA), and b) formulation as a highly viscous hydrogel. The vehicles prepared by applying (singly or in combination) these techniques, and two reference aqueous vehicles containing DAP-HCl were submitted to a series of biological tests on rabbits (miosis and reversion of mydriasis). When compared with an aqueous solution an aqueous solution, reconstituted prior to use from a freeze-dried formulation (marketed in Italy as Glamidolo^R, Angelini)

The topical administration of ophthalmic drugs from aqueous solutions (collyria) is characterized by a poor bioavailability and a short duration of action, as a result of a series of concomitant physiological factors (induced lacrimation, tear turnover, solution drainage etc.) which concur in removing the solution from the eye. These factors have been widely investigated and detailed in the relevant literature, and several approaches to extend the ocular residence time of topically applied medications have been reported (4). In the present study two such approaches, namely, a) salification of the basic drug with a polyanionic polymer and b) increased vehicle viscosity, were applied to the development of a long-acting ocular formulation for DAP. The effect of the said manipulations on the biological activity of a series of DAP vehicles was submitted to a preliminary verification “in vivo”, by performing miosis and reversion of tropicamide-induced mydriasis tests in rabbits