Enhanced buccal bioavailability of olmesartan through ultradeformable bilosomes loaded film: a novel approach for hypertension management

This study investigated the use of ultradeformable bilosomes (UBs)-loaded buccal films to overcome the limited oral bioavailability of olmesartan medoxomil (OLM), a poorly water-soluble antihypertensive. UBs were prepared via thin film hydration technique, and a 2⁴ factorial design evaluated the effects of phosphatidylcholine to bile salt (PC: BS) ratio, permeation enhancer (PE) type and amount, and sonication time on entrapment efficiency (EE), particle size (PS), zeta potential (ZP), and polydispersity index (PDI). The optimized formulation (UBs-12), comprising 50 mg Labrasol^® at an 8:1 PC: BS ratio and sonicated for 4 minutes, showed EE% of 67.9 ± 1.9%, PS of 279.8 ± 3.5 nm, ZP of -46.9 ± 1.4 mV, and PDI of 0.46 ± 0.02. It showed a markedly higher OLM release after 24 h (78.5 ± 2.4%) compared to conventional bilosomes and aqueous OLM suspension, as well as a significantly greater deformability index (18.2 ± 0.3) (<i>p</i> = 0.008) than conventional bilosomes. UBs-12 was incorporated into buccal films with favorable in vitro characteristics. Pharmacodynamic assessment in dexamethasone-induced hypertensive male rats demonstrated that UBs-12 films achieved a more pronounced and sustained blood pressure reduction compared to oral suspension. The films yielded a 1.68-fold increase in area under the antihypertensive effect-time curve and a 1.75-fold longer effect half-life. These results support UBs-loaded buccal films as a promising approach to enhance OLM bioavailability.