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Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats.
Colloids Surf B Biointerfaces. 2014 Mar 01; 115:286-94.CS

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+Show Affiliations

Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Department of Chemistry, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India. Electronic address: proftkpal@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24388859

Citation

Gorain, Bapi, et al. "Nanoemulsion Strategy for Olmesartan Medoxomil Improves Oral Absorption and Extended Antihypertensive Activity in Hypertensive Rats." Colloids and Surfaces. B, Biointerfaces, vol. 115, 2014, pp. 286-94.
Gorain B, Choudhury H, Kundu A, et al. Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats. Colloids Surf B Biointerfaces. 2014;115:286-94.
Gorain, B., Choudhury, H., Kundu, A., Sarkar, L., Karmakar, S., Jaisankar, P., & Pal, T. K. (2014). Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats. Colloids and Surfaces. B, Biointerfaces, 115, 286-94. https://doi.org/10.1016/j.colsurfb.2013.12.016
Gorain B, et al. Nanoemulsion Strategy for Olmesartan Medoxomil Improves Oral Absorption and Extended Antihypertensive Activity in Hypertensive Rats. Colloids Surf B Biointerfaces. 2014 Mar 1;115:286-94. PubMed PMID: 24388859.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats. AU - Gorain,Bapi, AU - Choudhury,Hira, AU - Kundu,Amit, AU - Sarkar,Lipi, AU - Karmakar,Sanmoy, AU - Jaisankar,P, AU - Pal,Tapan Kumar, Y1 - 2013/12/16/ PY - 2013/09/28/received PY - 2013/11/12/revised PY - 2013/12/09/accepted PY - 2014/1/7/entrez PY - 2014/1/7/pubmed PY - 2014/12/15/medline KW - Bioavailability KW - Caco-2 permeability KW - Hypertensive model KW - Nanoemulsion KW - Olmesartan medoxomil SP - 286 EP - 94 JF - Colloids and surfaces. B, Biointerfaces JO - Colloids Surf B Biointerfaces VL - 115 N2 - 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. SN - 1873-4367 UR - https://www.unboundmedicine.com/medline/citation/24388859/Nanoemulsion_strategy_for_olmesartan_medoxomil_improves_oral_absorption_and_extended_antihypertensive_activity_in_hypertensive_rats_ DB - PRIME DP - Unbound Medicine ER -