# Hypotension and antiphlogistic potential of empagliflozin ocular film: swelling and release kinetics

## TL;DR

This study explores using empagliflozin ocular films to lower eye pressure and reduce inflammation in diabetes patients.

## Contribution

The novel contribution is the development of an empagliflozin ocular film with colloidal silicon dioxide for controlled drug release and anti-inflammatory effects.

## Key findings

- Silicon dioxide-loaded films showed faster drug release and lower intraocular pressure.
- Empagliflozin demonstrated anti-inflammatory activity by binding to key inflammatory markers.
- A strong correlation was found between drug release and intraocular pressure reduction.

## Abstract

Empagliflozin (EMP) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used for the management of type 2 diabetes mellitus. The danger of glaucoma in type 2 diabetes mellitus patients is known to be reduced using SGLT2 inhibitors. Empagliflozin is also believed to reduce the level of inflammatory markers. The present work has been undertaken for monitoring intraocular pressure and anti-inflammatory activity using the empagliflozin ocular film formulation. The effect of colloidal silicon dioxide upon the dynamics of swelling and drug release performance was also studied.

Hydroxypropyl methylcellulose-based ocular film of empagliflozin was prepared, including silicon dioxide in different ratios as 1:0.00, 1:0.01, 1:0.02, 1:0.04, and 1:0.06 (namely, EMA0, EMA1, EMA2, EMA3 and EMA4, respectively) using casting and solvent evaporation. Swelling and drug release studies of the films were conducted in phosphate buffer solution (pH 7.4), and the kinetic mechanisms of swelling and drug release were evaluated. Intraocular pressure was measured after application of the film in the normotensive rabbit eye. Moreover, the anti-inflammatory effect was assessed using a rabbit ocular carrageenan-induced inflammation model.

Swelling behaviour followed Fickian mechanism in the order: EMA3<EMA2<EMA0<EMA4<EMA1, and partial relaxation with EMA3. Films containing silicon dioxide showed faster release than those without it (EMA0), following a diffusion pattern. The silicon dioxide-loaded film (EMA3) showed significantly lowered intraocular pressure and promising ocular anti-inflammation with favourable binding affinities of EMP to Interleukin-1β, Interleukin 6 and tumour necrosis factor-α. A good correlation between intraocular pressure and drug release was also established.

A hydroxypropyl methylcellulose-based ocular film containing empagliflozin and silicon dioxide could be used to manage intraocular pressure and inflammation in a controlled manner in patients with type 2 diabetes mellitus.