Abstract Purpose This study aimed to develop spanlastics-loaded buccal films to overcome the oral bioavailability limitations of olmesartan medoxomil (OLM), a sparsely water-soluble antihypertensive agent. Methods: OLM-loaded spanlastics were prepared using the ethanol injection method. A 2 4 factorial design was employed to investigate the effects of different variables on vesicles’ features and to identify the optimized spanlastic formula (OS). Vesicles were characterized in terms of entrapment efficiency (EE), particle size (PS), zeta potential (ZP), and polydispersity index (PDI). OS was further characterized in vitro, incorporated into buccal films, and its pharmacodynamic performance was assessed in a single-dose study in hypertensive rats, compared to orally administered OLM suspension. Results OS showed spherical vesicles with EE% of 67.7±2.97%, PS of 202.6±4.38 nm, ZP of ‒32.00±1.27 mV, and PDI of 0.272±0.00. OS showed markedly higher OLM release over 24 h compared to OLM suspension. Differential scanning calorimetry indicated drug amorphization. In vitro characterization, along with histopathological examination, demonstrated that OS-loaded films were well-tolerated and safe for buccal administration. Furthermore, pharmacodynamic evaluation revealed that these films significantly enhanced and sustained the antihypertensive effect of OLM, achieving a 1.68-fold increase in area under the antihypertensive effect-time curve and a 1.67-fold prolongation in effect half-life. Conclusion These findings confirm the enhanced and sustained antihypertensive effect of OLM delivered via spanlastics-loaded buccal films, highlighting them as a promising delivery system for OLM.
Elrady et al. (2026) studied this question.