The EyeFlowCell: Development of a 3D-Printed Dissolution Test Setup for Intravitreal Dosage Forms

Abstract

An in vitro dissolution model, the so-called EyeFlowCell (EFC), was developed to test intravitreal dosage forms, simulating parameters such as the gel-like consistency of the vitreous body. The developed model consists of a stereolithography 3D-printed flow-through cell with a polyacrylamide (PAA) gel as its core. This gel needed to be coated with an agarose sheath because of its low viscosity. Drug release from hydroxypropyl methylcellulose-based implants containing either triamcinolone acetonide or fluorescein sodium was studied in the EFC using a schematic eye movement by the EyeMovementSystem (EyeMoS). For comparison, studies were performed in USP apparatus 4 and USP apparatus 7. Significantly slower drug release was observed in the PAA gel for both model drugs compared with the compendial methods. Drug release from fluorescein sodium-containing model implants was completed after 40 min in USP apparatus 4, whereas drug release in the gel-based EFC lasted 72 h. Drug release from triamcinolone acetonide-containing model implants was completed after 35 min in USP apparatus 4 and after 150 min in USP apparatus 7, whereas this was delayed until 96 h in the EFC. These results suggest that compendial release methods may overestimate the drug release rate in the human vitreous body. Using a gel-based in vitro release system such as the EFC may better predict drug release.

Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid

“…The release of the active substance during the first three hours of the test decreased on average by 1.5–2 times compared to free cefuroxime, which is a significantly prolonged effect. This is probably because the solid dispersion of cefuroxime contains a complex of water-soluble compounds with high molecular weights in their composition [ 42 ]. During the release test, at first, the solvent against the concentration gradient tended to enter the polymer dispersion matrix through the dialysis membrane, which promoted the breakage of hydrogen bonds of the complex, allowed the release of the antibiotic from the matrix, and permitted its diffusion into the receptor medium.…”

Real-Time Monitoring Platform for Ocular Drug Delivery

“…In recent years, there has been progress in designing and reporting ocular in vitro models for preclinical testing in research. In vitro models have been designed to evaluate protein stability in simulated vitreous fluids (SVF) [ 19 ], to understand the effects of eye movements (EyeMos system) [ 20 , 21 ], and to evaluate the effect of SVF and aqueous outflow on drug release/clearance times (PK-Eye™ models) [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. PK-Eye™ model variants™ have also been reported in the literature [ 29 , 30 ].…”

Development of ARPE-19-Equipped Ocular Cell Model for In Vitro Investigation on Ophthalmic Formulations

“…Another in vitro test described in the literature combines a vitreous model [14] and a simple system described by Loch and colleagues [15] in an attempt to create an in vitro system resembling the vitreous body and the applied forces that move the depot [16]. This model, called EyeMoS [17], is composed of a spherical eye chamber, obtained by 3D printing, housed on a rotating device and filled with gel of polyacrylamide, coated in turn with a thin layer of agarose gel. The chamber is provided with an inlet channel (for injection) and an outlet channel.…”