A novel ocular in situ gelling delivery system optimizes the induction of diagnostic and preoperative mydriasis

Abstract

Purpose : Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Phenylephrine (PHE) and tropicamide (TPC) are widely used to induce mydriasis and several dosage forms of these two active ingredients (API) have been described. However, no optimal drug delivery strategy has reached the market. We hypothesized that an in situ gelling system (ISGS) for the delivery of PHE and TPC could induce a fast, long-lasting and efficient mydriasis following the topical administration of a single drop.

Methods : ISGS are liquid solutions instilled as eye drops, that undergo a sol to gel phase transition upon administration on the ocular surface. Thus, allowing prolonged ocular residence time and enhanced ocular bioavailability. The suitability of gelation was evaluated by rheological studies in a previous work.
Here, ISGS was evaluated in vivo on male New-Zealand albino rabbits (N=3). Mydriasis pharmacodynamics and ocular residence time were studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. One drop ISGS mydriasis profile was compared with mydriasis profiles of one drop of a control solution of PHE and TPC and to the administration regimen of CED; 4 drops of Mydriaticum 0.5% and 4 drops of Neosynephrine 10% with a five minutes interval between each drop.

Results : Instillation of ISGS resulted in an extended residence time on the ocular surface (> 5 hours). ISGS mydriasis profile exhibited a significant increase of intensity and duration compared to a control solution (p=0.004). Also, one drop ISGS mydriasis profile showed no significant difference with the mydriasis profile obtained following the administration regimen of CED (p=0.37).

Conclusions : A fast, long-lasting and efficient mydriasis was achieved following the administration of a single drop of ISGS. If confirmed clinically, ISGS could be an alternative to existing treatments, increasing patients comfort and reducing the risk of side effects by reducing the quantity of APIs administered by 4 to 8 fold.

This is a 2020 ARVO Annual Meeting abstract.

 

Pictures of New-Zealand albino rabbit eyes recorded before and until 5 hours following the administration of one drop of ISGS.

 

Mydriasis profiles (N=3) displayed as change in pupil diameter versus time following the administration of one drop of ISGS (A), one drop of a liquid control solution (Ctrl) and to the administration regimen of CED.