In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics

Abstract

Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached the market. The present work focuses on the formulation and evaluation of a mucoadhesive ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose (HEC) for the delivery of phenylephrine and tropicamide. First, in vitro drug release was studied to assess appropriate sustained drug delivery on the ocular surface region. Drug release mechanisms were explored and explained using mathematical modeling. Then, in situ gelling delivery systems were visualized using scanning electron microscopy illustrating the drug release phenomena involved. Afterward, cytotoxicity of the developed formulations was studied and compared with those of commercially available eye drops. Human epithelial corneal cells were used. Finally, mydriasis intensity and kinetic was investigated in vivo. Mydriasis pharmacodynamics was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. In situ gelling delivery systems mydriasis profiles exhibited a significant increase of intensity and duration compared with those of conventional eye drops. Efficient mydriasis was achieved following the administration of a single drop of in situ gel reducing the required amount of administered active ingredients by four-to eight-fold compared with classic eye drop regimen.

Novel Eye Drop Delivery Systems: Advance on Formulation Design Strategies Targeting Anterior and Posterior Segments of the Eye

“…The ion-sensitive in situ gel significantly delayed drug release and improved bioavailability compared with conventional eye drops [104]. Table 3 [101,102,105,106] lists ion-sensitive in situ gel eye drop delivery systems in the application of the anterior and posterior segments of the eye. Table 3.…”

Pre-Formulation Studies: Physicochemical Characteristics and In Vitro Release Kinetics of Insulin from Selected Hydrogels

“…The release profiles were assumed to be similar when f 1 was in the range of 0–15 and f 2 was in the range of 50–100. A value of 100 meant that the compared profiles were identical, and a value of 50 represented a 10% difference across all time points [ 40 ].…”

“…The release profiles were assumed to be similar when f 1 was in the range of 0-15 and f 2 was in the range of 50-100. A value of 100 meant that the compared profiles were identical, and a value of 50 represented a 10% difference across all time points [40]. The rheological and the textural parameters are important features of hydrogels indicating their functional properties.…”

New Preservative-Free Formulation for the Enhanced Ocular Bioavailability of Prostaglandin Analogues in Glaucoma

“…It has been reported that the tear fluid is entirely renewed within 2-3 min under physiological conditions, therefore leading to a fast clearance of the eye drops [54,55]. On the other hand, an increase in viscosity, as displayed for PFED, can lengthen the residence time of the eye drop on the ocular surface [30,[55][56][57]. Indeed, NaHA was added to the eye drop formulation to thicken the solution.…”