Chronological Delivery of Antihypertensive Drugs in Bilayered Core-in-Cup Buccoadhesive Tablets: In Vitro and In Vivo Evaluation

Abstract

Hypertension shows circadian blood pressure rhythms (day-night pattern) that urge the delivery of antihypertensive drugs at the right time in the desired levels. Thus, a bilayered core-in-cup buccoadhesive tablet was formulated that immediately releases olmesartan, to give a burst effect, and controls azelnidipine release, to prolong its therapeutic effect. The main challenge was the poor bioavailability of azelnidipine due to its poor aqueous solubility and first-pass effect. Hence, liquisolid compact buccoadhesive tablets were prepared to enhance solubility, dissolution profiles, and bypass the oral route. Two factorial designs were conducted to study the type and concentration effect of the mucoadhesive polymers on the dissolution and mucoadhesion of olmesartan and azelnidipine. Characterization studies were conducted regarding drug content, surface pH, water uptake, mucoadhesive strength, in vitro release, and ex vivo permeability. The core-in-cup olmesartan/azelnidipine buccoadhesive tablet showed similar release profile to the statistically optimized formulae of each drug. In vitro dissolution study showed enhanced release of azelnidipine than the directly compressed tablets, to comply with the regulatory standards of controlled release systems. In vivo pharmacokinetic study of olmesartan and azelnidipine conducted on human volunteers against Rezaltas® 10/8 mg tablet showed percentage relative bioavailability of 106.12 and 470.82%, respectively.

Liquisolid systems as a novel approach in formulation and manufacturing of solid dosage forms: Challenges and perspectives

“…An in vivo pharmacokinetic study in healthy human volunteers was conducted with an immediate release commercially available tablet as a control. Olmesartan was rapidly absorbed and reached higher maximum plasma concentration (Cmax) than the control, while azelnidipine showed a prolonged release profile with a significant increase in the extent of absorption (60).…”