Formulation of olopatadine hydrochloride viscous eye drops – physicochemical, biopharmaceutical and efficacy assessment using in vitro and in vivo approaches

• Published in: European journal of pharmaceutical sciences Vol. 166; p. 105906
• Main Authors: Račić, Andjelka, Čalija, Bojan, Milić, Jela, Jurišić Dukovski, Bisera, Lovrić, Jasmina, Dobričić, Vladimir, Micov, Ana, Vuković, Milja, Stepanović-Petrović, Radica, Krajišnik, Danina
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2021
• Subjects: HCE-T cell-based models; MTT cytotoxicity assay; Ocular itch test; Olopatadine hydrochloride; PAMPA; Viscous eye drops; PBS; Viscous eye drops; HCE-T; MTT cytotoxicity assay; HCE-T cell-based models; FT-IR; PAMPA; MTT; Olopatadine hydrochloride; LC-MS/MS; OLO; MCH; Ocular itch test; Papp; DSC; HEPES; TEER; UHPLC; HBSS; HPG; HPLC
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2021.105906

•Formulation and evaluation of olopatadine viscous eye drops was performed.•Combination of chitosan and hydroxypropyl guar gum was compatible with the drug.•The drug permeability was estimated using HCE-T cell-based models and PAMPA.•MTT assay demonstrated that the tested eye drops were non-toxic and well tolerated.•An ocular itch test on mice was employed for efficacy evaluation. The aim of this work was the formulation and the comprehensive evaluation of the viscous eye drops using vehicles containing medium chain chitosan (0.5% w/v), hydroxypropyl guar gum (0.25% w/v) and their combination as carriers for olopatadine (0.1% w/v). Physicochemical properties (appearance, clarity, pH, osmolality, viscosity and drug content) of the tested formulations were within acceptable ranges for the ophthalmic preparations, while DSC and FT-IR techniques demonstrated the compatibility between olopatadine and polymers. The drug permeability was successfully estimated in vitro using both HCE-T cell-based models (Model I and Model II) and the parallel artificial membrane permeability assay (PAMPA), considering the impact of chitosan as a permeation enhancer. The MTT cytotoxicity assay demonstrates that the tested formulations (diluted 10-fold in HBSS pH 5.5) were non-toxic and well tolerated. An ocular itch test on mice was carried out with the formulation containing the combination of polymers comparable with a commercially available olopatadine eye drops without viscosity enhancers. The tested eye drops produced a slightly higher anti-pruritic/analgesic-like effect than the commercial preparation. It could be assumed that the use of this viscous ophthalmic vehicle due to its advanced mucoadhesive properties and good safety profile is a feasible strategy to improve the efficacy of olopatadine. [Display omitted]