The present investigation was directed toward the development of effervescent tablets containing Levocetirizine dihydrochloride, with particular emphasis on evaluating how formulation parameters influence disintegration behavior and drug liberation within five minutes, employing a Box–Behnken experimental framework. The intrinsic bitterness of Levocetirizine dihydrochloride was successfully masked through the preparation of a 1:1 inclusion complex with β-cyclodextrin using the kneading technique. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses confirmed efficient molecular encapsulation of the drug within the cyclodextrin cavity. In the optimization design, the quantities of Crospovidone, sodium bicarbonate, and citric acid were considered as independent variables. A mathematical modeling approach enabled quantitative assessment of main and interactive effects, revealing that these formulation factors significantly modulated both disintegration time and the extent of drug release at five minutes. The optimized formulation exhibited rapid disintegration in aqueous medium, while dissolution studies in 0.1 N HCl demonstrated more than 90% drug release within five minutes. Conversely, in phosphate buffer at pH 6.8, drug release was substantially slower (35.4% within five minutes), thereby validating the effectiveness of the taste-masking strategy through restricted release in the oral cavity.