Design, Optimisation and Evaluation of Orally Disintegrating Tablets of Nicardipine Hydrochloride Prepared with a Natural Sweetener

Abstract

Nicardipine hydrochloride, a dihydropyridine calcium channel blocker used in hypertension and angina, is limited by an intensely bitter taste, poor aqueous solubility and a short half-life. This study aimed to design, optimise and evaluate orally disintegrating tablets (ODTs) of nicardipine hydrochloride using high-purity rebaudioside A as a natural taste-masking sweetener. ODTs were prepared by direct compression and optimised using a three-factor three-level Box–Behnken design with crospovidone, croscarmellose sodium and rebaudioside A as factors and disintegration time, wetting time, hardness and drug release at five minutes as responses. All models were significant (p < 0.0001, R² > 0.98). The optimised formulation (crospovidone 5.62%, croscarmellose sodium 5.48%, rebaudioside A 1.84%) showed disintegration time 13.9 ± 0.4 s, wetting time 17.5 ± 0.6 s, hardness 28.2 ± 0.8 N, friability 0.46%, drug content 99.4 ± 1.6% and 90.4% release within five minutes. Taste-panel scores were significantly higher than placebo (p < 0.001). The formulation was stable under accelerated and long-term conditions. In rats, it achieved higher and earlier Cmax (174.6 ng/mL at 0.86 h vs 148.2 ng/mL at 1.42 h), relative bioavailability 106.3% and a faster antihypertensive onset than the reference. A natural-sweetener-based ODT of nicardipine is thus a feasible, palatable and robust patient-friendly dosage form.

Keywords: Nicardipine hydrochloride; orally disintegrating tablet; rebaudioside A; natural sweetener; taste masking; Box–Behnken design.