Stability and Efficacy of Mucoadhesive Eye Drops Containing Olopatadine HCl: Physicochemical, Functional, and Preclinical In Vivo Assessment

Abstract

Background: The incorporation of polymers into drug delivery vehicles has been shown to be an effective strategy to prolong the residence time of active ingredients in the precorneal tear film and to increase ocular bioavailability. Objectives: The aim of this study was to develop novel, viscous eye drops containing olopatadine (OCH) as the active ingredient, polysaccharides hydroxypropyl guar gum (HPG), and sodium hyaluronate (SH), individually, and in combination as functional polymers. Methods: Viscous eye drops containing 0.1% OCH in combination with HPG (0.25%) and SH (0.4%), were prepared and evaluated for their physicochemical properties, rheological behavior, mucoadhesion, and preliminary stability. A novel rheological method was used to evaluate the resistance of the eye drops under simulated blinking conditions. In vivo efficacy was evaluated using an ocular itch test in mice to compare the formulations with a commercial product. Results: The formulations remained stable and transparent, with physicochemical parameters within acceptable ranges. Rheological studies confirmed pseudoplastic flow, with the HPG-SH combination exhibiting enhanced viscosity and shear-thinning properties for prolonged retention in the eye. Mucoadhesion was highest in SH-HPG formulations. During simulated blinking cycles, eye drops containing a combination of SH and HPG polymers fully regained their initial viscosity during the resting periods. Preliminary stability studies indicate that the formulated eye drops exhibit satisfactory physicochemical stability under various storage conditions. In vivo, OCH-SH and OCH-HPG-SH drops provided prolonged antipruritic and analgesic effects compared to the reference product. Conclusions: Polysaccharide-based innovative formulations improve OCH retention, enhancing therapeutic efficacy and patient compliance in the treatment of allergic conjunctivitis.

Keywords: eye drops; hydroxypropyl guar gum; mucoadhesivity; ocular itch test; olopatadine hydrochloride; rheological synergism; sodium hyaluronate; stability.

Figure 1

(A) Rheograms of the tested eye drops; (B) apparent viscosity as a function of shear rate.

Figure 2

Viscosity values of the tested eye drops under simulated eye blinking.

Figure 3

The effects of mucoadhesive eye drops with OCH (OCH-HPG, OCH-SH, and OCH-HPG-SH) and the reference product (Opatanol^®) on pruritic-like and nociceptive-like behavior in the ocular itch test in mice. Results are expressed as the number of histamine-induced scratching (A) and wiping (B) bouts, along with the percentage of antipruritic (a) and antinociceptive (b) activity. The columns in panels (A,B) (from left to right) correspond to the order of treatment groups (from top to bottom) in the respective bar graph legends. Columns/points represent the group mean ± standard error of the mean (n = 7–12). Statistical analysis was performed using two-way analysis of variance (ANOVA) followed by Tukey’s post hoc test (* p < 0.05 and *** p < 0.001 compared to the control group; # p < 0.05 compared to the reference formulation; § p < 0.05 for comparison between OCH-SH or OCH-HPG-SH and OCH-HPG).