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

Eur J Pharm Sci. 2021 Nov 1:166:105906. doi: 10.1016/j.ejps.2021.105906. Epub 2021 Jun 9.

Abstract

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.

Keywords: HCE-T cell-based models; MTT cytotoxicity assay; Ocular itch test; Olopatadine hydrochloride; PAMPA; Viscous eye drops.

MeSH terms

  • Animals
  • Biological Products*
  • Mice
  • Olopatadine Hydrochloride
  • Ophthalmic Solutions
  • Spectroscopy, Fourier Transform Infrared
  • Viscosity

Substances

  • Biological Products
  • Ophthalmic Solutions
  • Olopatadine Hydrochloride