Generic benzalkonium chloride-preserved travoprost eye drops are not identical to the branded polyquarternium-1-preserved travoprost eye drop: Effect on cultured human conjunctival goblet cells and their physicochemical properties

• Published in: Acta ophthalmologica (Oxford, England) Vol. 100; no. 7; pp. 819 - 827
• Main Authors: Hedengran, Anne, Freiberg, Josefine Clement, Hansen, Pernille May, Jacobsen, Jette, Larsen, Susan Weng, Harloff-Helleberg, Stine, Freude, Kristine, Boix-Lemonche, Gerard, Petrovski, Goran, Heegaard, Steffen, Kolko, Miriam
• Format: Journal Article
• Language: English; Norwegian
• Published: England Wiley Subscription Services, Inc 01.11.2022; John Wiley and Sons Inc
• Subjects: Antihypertensive Agents; Benzalkonium chloride; Benzalkonium Compounds - chemistry; Benzalkonium Compounds - pharmacology; Cell viability; Colorimetry; Eye; Generic drugs; Glaucoma; Goblet Cells; Humans; Interleukin 6; Interleukin-8; L-Lactate dehydrogenase; Lactate Dehydrogenases; Lactic acid; Mucin; Mucins; Ophthalmic Solutions - pharmacology; Original; pH effects; Physicochemical properties; Polyquaternium; Preservatives, Pharmaceutical - chemistry; Preservatives, Pharmaceutical - pharmacology; Travoprost - pharmacology; Viscosity; travoprost; benzalkonium chloride; goblet cells; glaucoma; polyquaternium-1; ocular surface
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/aos.15163

To investigate the effect of polyquaternium-1 (PQ)-preserved and benzalkonium chloride (BAK)-preserved travoprost eye drops on viability of primary human conjunctival goblet cell (GC) cultures and on secretion of mucin and cytokines. Furthermore, to evaluate the physicochemical properties of the branded travoprost eye drop Travatan® and available generics. The effect of travoprost eye drops was evaluated on GC cultures. Cell viability was assessed through lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin secretion was evaluated by immunohistochemical staining. Secretion of interleukin (IL)-6 and IL-8 was measured using BD Cytometric Bead Arrays. pH, viscosity, droplet mass, osmolality and surface tension were measured for all included eye drops. In the LDH assay, BAK travoprost caused significant GC loss after 2 hrs of incubation compared to the control. PQ travoprost caused no GC loss at any time point. Both PQ- and BAK travoprost caused secretion of mucin to the cytoplasma. No difference in IL-6 and IL-8 secretion was identified compared to controls. The pH values for the generics were lower (pH 6.0) than the pH value for Travatan (pH 6.7; p < 0.0001). The viscosity was lowest for Travatan, while the mean droplet mass was higher for Travatan (35 mg) than the generics (28-30 mg; p ≤ 0.0318). The osmolality and surface tension did not differ between the eye drops investigated. BAK travoprost caused GC loss, indicating that PQ preservation may be preferable in treatment of glaucoma. Furthermore, physicochemical properties of branded and generic travoprost eye drops can not be assumed to be identical.