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Abstract

ABSTRACT:Olmesartan medoxomil (OLM) is a lipophilic (log P = 4.31) antihypertensive drug suffering from limited oral bioavailability in humans (26%) due to its low aqueous solubility, uncontrolled enzymatic conversion to the active metabolite (Olmesartan; OL) and efflux by drug resistance pumps. Surmounting such limitations via incorporation of OLM into selfnanoemulsifying drug delivery systems (SNEDDS). Based on OLM-equilibrium solubility studies in various oils, surfactants and co-surfactants, Capmul ® MCM, Tween ® 20, Cremophor ® EL and polyethylene glycol -400 (PEG) were combined in different ratios to plot ternary phase diagrams. OLM-loaded SENDDS were developed and evaluated forparticle size, polydispersity index (PDI), zeta potential, self-emulsification time, morphology, drug released percentages after 5-min (Q 5min %), 1 hour (Q 1h %) and dissolution efficiency percentages (DE 1h %). The OL pharmacokinetics from SNEDDS (F6) and Benicar ® tablets were evaluated (LC-MS/MS) in rabbits. Spherical OLM-loaded SNEDDS were developed. The best-achieved SNEDDS (F6) showed short emulsification time (13 s), fine droplet size (60.00nm), low PDI (0.25), negative zeta potential (-14.4mV), promising dissolution parameters; Q 5min % (29.78%), Q 1h % (66.69%) and DE 1h % (47.96%) and enhanced in vivo absorption characteristics; shorter T max , higher C max and larger AUC (0−48h ; suggesting its potential for the enhancement of the oral absorption of practically insoluble drugs; like OLM.