Abstract
Purpose :
Nepafenac (NPF) and Dexamethasone Phosphate (DEX-P) are two of the most used anti-inflammatory drugs in ocular surgery. Multiple daily instillations of the single drugs, poor compliance of the NPF suspensions as well as preservatives toxicity in commercial formulations are the strong weaknesses of the current pre- and/or post-surgery protocols, especially in elderly patients. The aim of our study was the development of a better tolerated preservative-free fixed combination NPF and DEX-P.
Methods :
0.1% NPF and 0.1% DEX-P (MDV1605) were formulated in cyclodextrin aqueous solution in presence of a viscosity-incresing agent (hyaluronic acid). MDV1605 shelf-life stability studies were conducted according to International Conference on Harmonization (ICH) guidelines: NPF, DEX-P and their degradation products were evaluated by validated HPLC-DAD methods. Ocular viability test of MDV1605 were led in comparison with commercial NEVANAC (Alcon) and DEXAVISION (FB Vision) and their vehicles, by employing the human corneal epithelial cell line HCE-2. Cytotoxicity was determined 24h after exposure to scalar concentrations of the test materials (NEVANAC, DEXAVISION, MDV1605 and their vehicles) using MTT assays.
Results :
Stability studies at 25°C (ICH) showed a good stability for both DEX-P and NPF in the MDV1605 formulation: concentration of DEX-P was 99.5% and of NPF was 98.6% at 24 months. Degradation products were all lower than 1% and have been fully characterized. Results of in vitro viability tests after 24h of incubation showed that the MDV1605 formulation caused a lower toxicity compared to NPF commercial formulation, viability rate was 76% for MDV1605 and 40% for NEVANAC.
Conclusions :
MDV1605 eye drops solution was stable at room temperature as well as much less cytotoxic in the MTT assay of the viability study than NEVANAC.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.