Azelastine Hydrochloride

Azelastine hydrochloride is a selective, nonsedating H1 antagonist with a phthalazinone chemical structure. As a second-generation antihistamine, it acts as a competitive antagonist at H1 receptors with affinity several times greater than chlorpheniramine, and has only weak affinity for H2 receptors. Beyond antihistaminic effects, azelastine demonstrates mast cell stabilization through reversible inhibition of voltage-dependent L-type calcium channels, which inhibits degranulation and release of histamine and other inflammatory mediators including leukotrienes, interleukin-1β, tumor necrosis factor-α, endothelin-1, and platelet-activating factor.
Azelastine modifies both immediate- and late-phase allergic reactions. It directly antagonizes histamine effects on nerve and vascular tissues to relieve pruritus, hyperemia, edema and chemosis. Through IgE-dependent and IgE-independent inhibition of mast cell degranulation, it diminishes the second wave of biochemical mediators that increase mucus secretion and promote inflammatory cell infiltration. Azelastine also downregulates intercellular adhesion molecule-1 on conjunctival epithelial cells, minimizing late-phase ocular surface damage. These multiple mechanisms classify azelastine as a dual-acting anti-inflammatory drug effective for allergic conjunctivitis with twice-daily dosing.

Fig. 1 Multiple pathways are responsible for the antiallergic effects of azelastine. (Williams P B.; et al. 2010)

Azelastine hydrochloride-loaded poloxamer 407 micelles with gellan gum were developed using thin film hydration method for temperature-sensitive in situ gelling ocular delivery. The optimized formulation exhibited particle size below 100 nm with low gelation temperature, which increased retention time at the administration site and provided controlled drug release. In vitro release showed 85 to 89 percent drug release at the 10th hour, while in vivo analysis demonstrated similar efficacy to the marketed AzelastTM formulation. The controlled release in situ temperature-sensitive gel successfully reduced allergic conjunctivitis symptoms, offering a promising approach for improved ocular drug delivery with enhanced patient compliance.

Fig. 2 Azelastine hydrochloride-loaded poloxamer 407 micelles with gellan gum for allergic conjunctivitis symptoms. (Ranade V.; et al. 2023)