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.

Graphical Abstract

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Correspondence to Sara Nageeb El-Helaly.

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This study design was approved by the Cairo University Research Ethics Committee (serial number of the protocol: PI 1189) and conducted with respect to the world medical association’s code of ethics of Declaration of Helsinki 2013.

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Rashad, A.A., Nageeb El-Helaly, S., Abd El Rehim, R.T. et al. Chronological Delivery of Antihypertensive Drugs in Bilayered Core-in-Cup Buccoadhesive Tablets: In Vitro and In Vivo Evaluation. AAPS PharmSciTech 21, 21 (2020). https://doi.org/10.1208/s12249-019-1575-9

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KEY WORDS

  • azelnidipine
  • olmesartan
  • liquisolid compacts
  • core-in-cup
  • buccoadhesive tablets