Comparative characteristics of eye drops used for the treatment of glaucoma in an experimental model of dry eye

Purpose of the work is a comparative study of the effect of different concentrations of the excipient carbomer on the local bioavailability and local irritant effect of brinzolamide and timolol in an experimental model of dry eye syndrome (DES). Material and methods. The study was performed on 35 sexually mature male rabbits of the Soviet Chinchilla breed. The effect of Brinarga eye drops (INN brinzolamide + timolol) containing carbomer 4.2 mg as an excipient (Sentiss Pharma Pvt. Ltd., India) and the comparison drugs — Preparation 1 (original) and Preparation 2 (generic, European manufacturer), containing INN brinzolamide + timolol and carbomer 4.0 mg, when instilled into the conjunctival sac every 12 hours for 14 days was studied. The local irritant effect of eye drops on the cornea of the eye and the bioavailability of the active substances included in all the studied drops were assessed on an experimental model of dry eye syndrome, which was reproduced by daily instillation of 1 drop of 1 % atropine sulfate into experimental animals 3 times a day for 5 days. Results. It was found that Brinarga eye drops containing 4.2 mg/ml carbomer 974P do not aggravate the course of DES and do not have a local irritant effect. On the contrary, their use is accompanied by a partial correction of the pathological condition (although it does not lead to complete restoration of corneal moisture to the values of the intact eye), unlike the existing analogs — Preparation 1 and Preparation 2, containing carbomer 974P at a concentration of 4.0 mg/ml. At the same time, Preparation 2 (generic, European manufacturer) caused a pronounced local irritant effect (total score 7.2 ± 1.2), which led to its early exclusion from the experiment. At 60 min, the maximum measured concentration of brinzolamide and timolol (Brinarga) in the aqueous humor of the anterior chamber during DES significantly exceeded that of Preparation 1 and Preparation 2. Conclusion. Increasing the concentration of carbomer to 4.2 mg/ml facilitates the passage of brinzolamide/timolol (Brinarga) through the tissue barrier of the eye and prevents presystemic elimination due to imparting optimal viscometric characteristics to the dosage form.

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