title: Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats.
abstract: Olmesartan medoxomil (OM) is hydrolyzed to its active metabolite olmesartan by the action of aryl esterase to exert its antihypertensive actions by selectively blocking angiotensin II-AT1 receptor. Poor aqueous solubility and uncontrolled enzymatic conversion of OM to its poorly permeable olmesartan limits its oral bioavailability. The aim of the current study was to formulate a novel nanoemulsion of OM to improve its pharmacokinetics and therapeutic efficacy. The oil-in-water (o/w) nanoemulsion of OM was developed using lipoid purified soybean oil 700, sefsol 218 and solutol HS 15. We have characterized the nanoemulsions by considering their thermodynamic stability, morphology, droplet size, zeta potential and viscosity and in vitro drug release characteristics in fasting state simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.5). The thermodynamically stable nanoemulsions comprises of spherical nanometer sized droplets (<50 nm) with low polydispersity index showed enhanced permeability through the Caco-2 cell monolayer. The concentration of active olmesartan in rat plasma following oral absorption study was determined by our validated LC-MS/MS method. The result of the pharmacokinetic study showed 2.8-fold increased in area under the curve (AUC0-27) of olmesartan upon oral administration of OM nanoemulsion and sustained release profile. Subsequent, in vivo studies with nanoemulsion demonstrated better and prolonged control of experimentally induced hypertension with 3-fold reduction in conventional dose. By analysing the findings of the present investigations based on stability study, Caco-2 permeability, pharmacokinetic profile and pharmacodynamic evaluation indicated that the nanoemulsion of OM (OMF6) could significantly enhance the oral bioavailability of relatively insoluble OM contributing to improved clinical application.
authors.affiliation: Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
authors.forename: Bapi
authors.initials: B
authors.lastname: Gorain
authors.affiliation: Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
authors.forename: Hira
authors.initials: H
authors.lastname: Choudhury
authors.affiliation: Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kundu
authors.affiliation: Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
authors.forename: Lipi
authors.initials: L
authors.lastname: Sarkar
authors.affiliation: Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
authors.forename: Sanmoy
authors.initials: S
authors.lastname: Karmakar
authors.affiliation: Department of Chemistry, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
authors.forename: P
authors.initials: P
authors.lastname: Jaisankar
authors.affiliation: Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India. Electronic address: proftkpal@gmail.com.
authors.forename: Tapan Kumar
authors.initials: TK
authors.lastname: Pal
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D004553:Electric Conductivity; D004655:Emulsions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D053758:Nanoparticles / Q000648:ultrastructure; D000068557:Olmesartan Medoxomil; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012031:Refractometry; D055672:Static Electricity; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D013816:Thermodynamics; D014783:Viscosity / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D004655:Emulsions; D007093:Imidazoles; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil
keywords: Bioavailability; Caco-2 permeability; Hypertensive model; Nanoemulsion; Olmesartan medoxomil