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Barbara Melilli, Maria Grazia Saita, Danilo Aleo, Sandro Dattilo, Sergio Mangiafico, Melina Cro, Sebastiano Mangiafico; New Water Based Drug Delivery System for Azithromycin Eye drops (MDV1226). PK Study in Rats vs Oily Azyter.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1087. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The aim of the study was comparing azithromycin concentration in the cornea and in the bulbar conjunctiva after instillation of 1.5% macrolide antibiotic hyaluronic acid/cyclodextrin based (MDV1226) or oil based (Azyter) formulations in rats.
Sprague Dawley rats were randomly divided in two groups of 28 animals. One group was instilled with MDV1226 a new eye drops formulation containing sulfobutylether cyclodextrins, hyaluronic acid, EDTA and phosphate buffer (pH=6.8-7.2), while the remaining rats received Azyter. Each group was further divided into 7 subgroups of 4 rats, to be sacrificed at the different time points after last instillation. Before treatment, rats were anesthetized by exposure to sevorane for a few seconds. 30 µl of each drug formulation was dosed by instilling 3 times 10 µl, at 1 min interval in both eyes by means a plastic disposable pipette tip. Rats were sacrificed at 5, 15, 30 min; 1, 4, 8 and 24 hr after the last 10 µl eye drops instillation. Cornea and bulbar conjunctiva from both eyes were collected, weighed and stored at −20°C until analysis. Drug levels in tissue samples were measured by using LC-MS method.
After topical instillation, MDV1226 and Azyter reached the highest concentration in the cornea and in the bulbar conjunctiva at same Tmax (5 min,1st sampling time). Azithromycin levels were significantly greater in the conjunctiva then in the cornea. Antibiotic Cmax after MDV1226 in the cornea was 2.2 fold higher than after Azyter (80.03 vs 36.35 µg/g, respectively), while in the bulbar conjunctiva Cmax were comparable, 111.47 and 111.63 µg/g for MDV1226 and Azyter, respectively.AUC(0.083-24h) [(µg/g) x h] values in the cornea were 69.07 and 82.09, while in the bulbar conjunctiva were 168.83 and 207.11 for MDV1226 and Azyter® respectively.
This exploratory study on rat model, showed that the extent of bioavailability (AUC) of MDV1226 formulation is comparable with Azyter formulation in the bulbar conjunctiva as well as in the cornea.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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