Synergism of polysaccharide polymers in antihistamine eye drops: Influence on physicochemical properties and in vivo efficacy

• Published in: International journal of pharmaceutics 2024-04, Vol.655, p.124033-124033, Article 124033
• Main Authors: Račić, Anđelka, Jurišić Dukovski, Bisera, Lovrić, Jasmina, Dobričić, Vladimir, Vučen, Sonja, Micov, Ana, Stepanović-Petrović, Radica, Tomić, Maja, Pecikoza, Uroš, Bajac, Jelena, Krajišnik, Danina
• Format: Article
• Language: English
• Subjects: HCE-T cell-based models; Ketotifen hydrogen fumarate; Mucoadhesivity; Ocular itch test; Polysaccharide polymers; Rheological synergism
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124033

[Display omitted] •Rheological and mucoadhesive synergism of polymers has been established.•The combination of hydroxypropyl guar gum with chitosan or hyaluronate was effective.•The drug permeability was estimated using HCE-T cell-based models.•MTT assay demonstrated that the tested eye drops were non-toxic and well tolerated.•An ocular itch test on mice revealed improved effect of ophthalmic ketotifen. The incorporation of polymers into drug delivery vehicles has been shown to be a useful approach to prolong the residence time of drugs in the precorneal tear film and to improve penetration into biological membranes. The main objective of this research was to formulate novel viscous eye drops with ketotifen as the active ingredient, containing the polysaccharides: chitosan (MCH), hydroxypropyl guar gum (HPG) and hyaluronic acid (SH) alone and in combination as functional polymers. DSC and FT-IR techniques showed the compatibility between ketotifen and polymers. Physicochemical and rheological analysis at ambient and simulated physiological conditions, as well as the evaluation of mucoadhesive properties showed that vehicles containing combinations of polymers have suitable physicochemical and functional properties with demonstrated synergism between combined polymers (MCH and HPG i.e. SH and HPG). The drug permeability was successfully estimated in vitro using HCE-T cell-based models. MTT cytotoxicity assay demonstrates that the tested formulations were non-toxic and well tolerated. In vivo preclinical study on mice revealed that both vehicles containing mixed polymers enhanced and prolonged the antipruritic/analgesic-like effect of ophthalmic ketotifen. Based on these results, both combinations of polysaccharide polymers, especially SH-HPG, could be considered as potential new carriers for ketotifen for ophthalmic use.