Design and in vivo pharmacokinetic evaluation of a once-daily immediate- and extended-release bilayer tablet of bepotastine salicylate

Aiming to provide rapid and extended drug release and increase patient adherence, bepotastine salicylate (BEP-S), a selective antihistamine, was formulated into a once-daily bilayer tablet (BLT). The BLT, consisting of immediate-release (IR) and extended-release (ER) layers, was prepared via direct compression and optimized based on mechanical strength, content uniformity, and dissolution performance. The optimized BLT first rapidly released 50% of the BEP-S within 1 h and then provided extended BEP-S release for more than 12 h. In a pharmacokinetic study in beagle dogs, the maximum drug concentration and extent of drug absorption of the once-daily BLT system were comparable to those of the twice-daily IR tablet. The half-life of the once-daily BLT under fasted and fed conditions was longer than that of the twice-daily tablet, with no significant differences in maximum plasma concentration or area under the plasma concentration–time curve between the tablet types. The optimized BLT was stable for 6 months under accelerated conditions (40°C/75% relative humidity); the appearance, drug content, impurities, and dissolution of the BLT did not notably change during this period. In conclusion, the developed BEP-S BLT is a promising once-daily oral formulation with appropriate IR/ER release characteristics and a bioequivalent pharmacokinetic profile.