Novel in situ gelling ophthalmic drug delivery system based on gellan gum and hydroxyethylcellulose: Innovative rheological characterization, in vitro and in vivo evidence of a sustained precorneal retention time

Achieving drug delivery at the ocular level encounters many challenges and obstacles. In situ gelling delivery systems are now widely used for topical ocular administration and recognized as a promising strategy to improve the treatment of a wide range of ocular diseases. The present work describes the formulation and evaluation of a mucoadhesive and ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose for the delivery of phenylephrine and tropicamide. First, physico-chemical characteristics were assessed to ensure suitable properties regarding ocular administration. Then, rheological properties such as viscosity and gelation capacity were determined. Gelation capacity of the formulations and the effect of hydroxyethylcellulose on viscosity were demonstrated. A new rheological method was developed to assess the gel resistance under simulated eye blinking. Afterward, mucoadhesion was evaluated using tensile strength test and rheological synergism method in both rotational and oscillatory mode allowing mucoadhesive properties of hydroxyethylcellulose to be point out. Finally, residence time on the ocular surface was investigated in vivo, using cyanine 5.5 dye as a fluorescent marker entrapped in the in situ gelling delivery systems. Residence performance was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. Fluorescence intensity profiles pointed out a prolonged residence time on the ocular surface region for the developed formulations compared to conventional eye drops, suggesting in vitro/in vivo correlations between rheological properties and in vivo residence performances.