Optimizing Fast-Dissolving Tablets of Ketotifen. Impact of Sodium Bicarbonate and Citric Acid in Formulation and Evaluation

Abstract

The research aimed to develop and assess fast-dissolving tablets (FDT) of ketotifen, a second-generation noncompetitive H1-receptor blocker, due to its poor oral bioavailability resulting from rapid first-pass effect (~50%) and poor solubility despite excellent permeability within the II-class of the biopharmaceutical classification system (BCS). The methodology involved formulating ketotifen with various excipients, including sodium bicarbonate, citric acid, menthol, polyvinyl pyrrolidone (PVP), aspartame, magnesium stearate, saccharin sodium, and dextrose. The combination of sodium bicarbonate and citric acid served as a fast-disintegrating agent by evolving carbon dioxide. Employing 23 factorial designs, the study assessed the impact of sodium bicarbonate (X1), citric acid (X2), and menthol (X3) on FDT performance. Batch A, exhibiting desirable characteristics, demonstrated weight variation (200±0.53), thickness (3.52±0.12 mm), hardness (2.87±0.23), friability (0.55±0.12), disintegration time (16±3 s), drug content uniformity (99.45±0.23), wetting time (3±1 s), and water absorption ratio (19.23±0.43). The primary contributor to fast tablet disintegration was identified as the high concentration of sodium bicarbonate rather than citric acid. All batches adhered to the Peppas Korsmeyer model, signifying Fickian Diffusion (Higuchi Matrix) as the drug release mechanism. In conclusion, the study showed the pivotal role of sodium bicarbonate concentration in facilitating rapid tablet disintegration, emphasizing its significance over citric acid concentration.