Implications for Ophthalmic Formulations: Ocular Buffers Show Varied Cytotoxic Impact on Human Corneal–Limbal and Human Conjunctival Epithelial Cells

Abstract

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BX795-Organic Acid Coevaporates: Evaluation of Solid-State Characteristics, In Vitro Cytocompatibility and In Vitro Activity against HSV-1 and HSV-2

“…However, as BX795 is intended to be developed for topical vaginal and ocular delivery, the option of counterions to develop the salt form narrowed significantly. Organic carboxylic acids such as maleic acid, fumaric acid, tartaric acid, and citric acid have been previously used either for the development of salts of drugs intended for vaginal and/or ocular delivery or as a component in the products intended for vaginal and/or ocular delivery [13][14][15][16][17][18][19]. Taurine is found in human uterine fluid, and taurine eye drops are commercially available, indicating its suitability for vaginal and ocular delivery [20][21][22].…”

Allergie und Trockenes Auge

“…An der Augenoberfläche führt BAK zu einer Reduktion der konjunktivalen Becherzellen mit konsekutiver mangelnder Muzinsekretion, zu einer Schädigung der Lipidphase des Tränenfilms, zu einer erhöhten Tränenfilmosmolarität, zum Lösen von Tight Junctions des kornealen Epithels und damit zu einer stärkeren Penetration, zu einer Schädigung des subbasalen kornealen Nervenplexus und zu einer verstärkten Aktivität von proinflammatorischen Zytokinen an der Augenoberfläche [20]. Auch höher konzentrierte Phosphat-Puffer in Augentropfen können zu zytotoxischen Effekten an limbalen Stammzellen und konjunktivalen Epithelzellen führen [21].…”

<p>A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments</p>

“…Buffers are not only necessary to stabilize a formulation’s pH for optimal solubility, tolerability, and activity but should also simulate the natural system of the tear film. 92 To date, the most commonly used buffers in ophthalmic formulations include citrate, phosphate, Tris-HCl, and borate. 92 Although AEs with citrate, Tris-HCl, and borate are not commonly reported in the literature, phosphate buffers may induce corneal calcification.…”

“… 92 To date, the most commonly used buffers in ophthalmic formulations include citrate, phosphate, Tris-HCl, and borate. 92 Although AEs with citrate, Tris-HCl, and borate are not commonly reported in the literature, phosphate buffers may induce corneal calcification. 92 In a recent study evaluating buffer-induced cytotoxicity in a human corneal epithelial and conjunctival cell model, both citrate and phosphate buffers resulted in significant cytotoxic effects at high concentration levels and long incubation times in a cell model of ocular epithelial tissue.…”

“… 92 Although AEs with citrate, Tris-HCl, and borate are not commonly reported in the literature, phosphate buffers may induce corneal calcification. 92 In a recent study evaluating buffer-induced cytotoxicity in a human corneal epithelial and conjunctival cell model, both citrate and phosphate buffers resulted in significant cytotoxic effects at high concentration levels and long incubation times in a cell model of ocular epithelial tissue. 92 For currently approved cyclosporine A formulations, sodium hydroxide and sodium phosphate monobasic dihydrate are used as buffering agents for cyclosporine 0.09% ophthalmic solution (OTX-101), 81 while sodium hydroxide is the sole buffering agent in both cyclosporine A 0.05% ophthalmic emulsion and cyclosporine A 0.1% ophthalmic emulsion.…”