Olmesartan Medoxomil

Olmesartan medoxomil is a pro-drug that is deesterified in the intestinal tract to produce the active metabolite olmesartan. The active metabolite undergoes no additional metabolic change and does not interact with cytochrome P450 enzymes. Olmesartan is a potent angiotensin II receptor blocker with high selectivity for the type 1 receptor subtype and shows insurmountable antagonism against the AT1 receptor in vascular tissues. This antagonistic mode could be attributed to tight binding of the drug to the receptor.
Key structural elements of olmesartan medoxomil include a hydroxyalkyl substituent at the imidazole 4-position and a hydrolyzable ester group at the imidazole 5-position. Inter- and intramolecular hydrogen bonding involving these groups may contribute to the potentiation of antagonist activity. Oral administration of olmesartan medoxomil produces a potent and long-lasting antihypertensive action without inducing tachycardia. Head-to-head comparisons with other angiotensin receptor blockers have revealed that olmesartan medoxomil is superior to these other agents in lowering blood pressure.

Fig. 1 The antihypertensive mechanism of angiotensin receptor blockers. (Mire D E.; et al. 2005)

Solid lipid nanoparticles of olmesartan medoxomil were prepared by solvent emulsion-evaporation method to enhance the oral bioavailability of the drug. The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 with an average particle size of 100 nm, polydispersity index of 0.291, zeta potential of -23.4 mV and 78 percent entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of the drug from solid lipid nanoparticles when compared to that of plain drug on oral administration.

Fig. 2 Pareto charts of particle size and zeta potential. (Nooli M.; et al. 2017)