Muco-adhesive buccal tablets of candesartan cilexetil for oral delivery: preparation, in-vitro and ex-vivo evaluation

Abstract

Candesartan cilexetil (CC) is an angiotensin II-receptor blocker (ARB). The antihypertensive effect of CC 4-16 mg/day was as great as that of other once-daily dosage regimens. Candesartan cilexetil has high first-pass metabolism and low oral bioavailability. The bioavailability of such drugs may be significantly improved if delivered through the buccal route; hence mucosal delivery is one of the alternative methods of systemic drug delivery. This study’s objective was to develop mucoadhesive buccal tablets of candesartan cilexetil using carbopol-934P, hydroxyl propyl methyl cellulose (HPMC), Eudragit RLPO, and sodium carboxy methyl cellulose (Na-CMC) as mucoadhesive polymers. Prepared CC buccal tablet formulations were evaluated for an optimized system based on physicochemical properties, ex-vivo residence time, in-vitro, and ex vivo permeation studies. The evaluation parameters of the tablets were within the acceptable Pharmacopoeial limits. However, the swelling and bio-adhesive time were increased with increasing polymer concentrations. The in-vitro release research shown that buccal tablets with sodium carboxy methyl cellulose (Na-CMC) exhibited a higher release than all other formulations and have been considered as optimized CC formulation. The release mechanism from kinetic methods suggests that the drug release follows zero-order kinetics with a diffusion mechanism. Further, in-vivo research in animal fashions is required to prove the bioavailability performance of the formulation.
 Keywords: Candesartan cilexetil, mucoadhesive buccal tablets, first-pass metabolism, bioavailability.