Fexofenadine Hydrochloride

Fexofenadine hydrochloride acts as a selective, non-sedating H1 receptor antagonist that competitively inhibits histamine binding at peripheral H1 receptors without significant penetration of the blood-brain barrier. The drug exhibits minimal affinity for cholinergic and α-adrenergic receptors, resulting in a lack of anticholinergic side effects. Beyond H1 receptor antagonism, fexofenadine demonstrates additional anti-inflammatory properties including inhibition of leukotriene C4, D4 and E4 production, suppression of prostaglandin E2 and F2α, competitive inhibition of cyclooxygenase-2, and reduction of iNOS-mediated nitric oxide generation. Fexofenadine also decreases expression of multiple cytokines and adhesion molecules including ICAM-1, VCAM-1, RANTES, and various matrix metalloproteinases, and diminishes eosinophil adherence and chemotaxis. The drug is rapidly absorbed with peak plasma concentrations achieved within one to two hours, with maximum histamine inhibition occurring at the same time point.

Fig. 1 Mechanisms of action of Fexofenadine on components of the immune system. (Axelrod D, Bielory L. 2008)

Fexofenadine hydrochloride was loaded into cubosomal nanoparticles using glyceryl mono-oleate as the oil phase and poloxamer 407 as stabilizer at weight ratios of 8:2 and 7:3. Transmission electron microscopy revealed spherical and polygonal nanostructures arranged in honeycomb organization. In situ rabbit intestinal perfusion studies demonstrated that P-glycoprotein efflux contributed to the poor intestinal absorption of fexofenadine from simple aqueous solution, but incorporation into cubosomes significantly enhanced membrane transport parameters. In vivo anti-inflammatory evaluation using carrageenan-induced rat paw edema showed that cubosomal encapsulation significantly enhanced the efficacy of fexofenadine compared to aqueous dispersion.

Fig. 2 Preparation and characterization of Fexofenadine hydrochloride cubosomal nanoparticles. (Sultan A A.; et al. 2022)