Abstract
Purpose :
Endophthalmitis is a devastating unmet medical need of Ocular Surgery. Preoperative topical antibiotic prophylaxis may allow to reduce the risk but it is one of the main causes of the development of bacterial resistance. The solution lies in the topical use of antiseptics: in particular iodine and its pro-drug Povidone iodine (PVP-I) which has a very wide antimicrobic spectrum of activity. Unfortunately ophthalmic solutions available worldwide are too high in PVP-I concentrations (5% or 10%) and are poorly tolerated and toxic for the conjunctiva and the cornea. Stabilization of well tolerated low-concentration (< 1%) PVP-I aqueous formulation is very challenging. Aim of our study was the preparation of a stable aqueous well tolerated 0.6% PVP-I eye drops formulation (MDV0911ID).
Methods :
MDV0911ID is a 0.6% PVP-I aqueous stable and transparent nanoemulsion containing Sodium Hyaluronate (SH), medium chain triglycerides (MCT) and a Smooth Surfactant (SS). The formulation was stored in glass bottles with bromobutyl rubber dropper and a polypropylene screw cap. Stability was evaluated under different ICH recommended conditions, compared with an aqueous PVP-I formulation (MDV0911IC) at the same pH and Osmolarity. Chemical stabilities were evaluated with a spectrophotometric method (Agilent Cary UV-Vis Dual-Beam at 375nm). Ocular biocompatibility Tests (Ocular Irritation Test and Cytotoxicity Test) were conducted by the reconstructed Human Corneal Epithelium Cells (HCE SkinEthic model).
Results :
Stability study showed a strong reduction of the PVP-I concentration in both formulations at 25°C after 6 months (60% in MDV0911ID and 30% in MDV0911IC). The title after 24 months at 4°C was of PVP-I was 93% in the IODIM formulation and only 80% in the MDV0911IC. The ocular biocompatibility test results showed that the MDV0911ID product is classified as Not Irritant (NI) and Not Cytotoxic (NC).
Conclusions :
Low-concentration (0.6%) PVP-I aqueous nanoemulsion formulation, MDV0911ID, resulted stable under refrigeration for at least 24 months. The SH-MCT-SS vehicle formed a nanoemulsion able to entrap the gaseous free iodine preventing and/or slowing down his leaking through the plastic. MDV0911ID eye drops can be used as a traditional topical ocular formulation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.