Systems for sustained ocular drug delivery: a review of stimuli-sensitive in situ gel-forming systems

摘要

Formulation development for ophthalmic drug delivery is one of the most challenging fields for investigators due to various limitations enforced by the eye. It includes factors such as specific features of the eye, the accuracy of the dose to be administered and the tear turnover rate affecting drug residence time, which causes different patterns of absorption. The conventional formulations such as solutions, suspensions and ointments show some constraints such as increased precorneal elimination, high variability in efficiency affecting bioavailability of drug and blurred vision due to the bases of the ointment formulations. In situ stimuli-activated gel-forming systems are liquid upon instillation and undergo phase transition in the ocular cul de sac to form a visco-elastic gel as a response to environmental changes such as temperature, pH or ionic strength. In the past few years, a number of new temperature-, pH- and ion-induced in situ gel-forming systems have been reported for sustained ophthalmic drug delivery. This review includes a description of various stimuli, associated with the ocular environment, which are proposed for use on such polymeric systems to achieve prolonged contact time of drugs with the cornea and to increase drug bioavailability.