Abstract
Purpose :
Treatment for ocular inflammation includes intravitreally administered corticosteroid treatments which are plagued by inconsistent delivery and inability to maintain significant level of drug for a long period of time. This study proposes that sustained release of dexamethasone via a polymeric implant is an ideal solution for long term (> 6 months) delivery to treat chronic inflammation. This study demonstrates dexamethasone release from an EVA implant and highlights the ability to tune the release rate of a therapeutic with various loading percentages and polymer grades.
Methods :
Powdered EVA with vinyl acetate contents of 28% and 40% were blended with dexamethasone at loading levels of 20% and 50%. These blends were compounded via hot melt extrusion (HME) on a 11mm twin screw extruder to produce four formulations. For each formulation, implants (N=6) were cut and weighed before placing them into Eppendorf conical tubes containing 5 mL buffer solution (pH =7.4). The tubes were placed into temperature-controlled incubators at 37 °C and 100 rpm. Samples were pulled at 1, 2, 7, 14, 21, 28 days and release were calculated via ultra-performance liquid chromatography (UPLC) method with thermo Fisher Scientific Vanquish UPLC equipped with an Ultra C18 column at 23 °C.
Results :
All formulations demonstrated dexamethasone release at day one. 50% loaded formulations released dexamethasone at a higher concentration when compared to 20%-loaded formulations. EVA with 40% VA and 50% loaded with dexamethasone released 2.36 mg dexamethasone compared to 1.21 mg for EVA with 28% VA and loaded 20% at 28 days.
Conclusions :
An EVA implant achieves sustained release of dexamethasone. Altering VA content is a tunable implant parameter that can be used to achieve the desired release profile of dexamethasone. The loading percentage has a larger effect on the release rate compared to the VA percentage in EVA. The demonstrated 1-month release rate, in tandem with modeling, provides evidence that an EVA implant can deliver dexamethasone for greater than 6 months.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.