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Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion.
Regul Toxicol Pharmacol. 2016 Dec; 82:20-31.RT

Abstract

Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients.

Authors+Show Affiliations

Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India; Faculty of Pharmacy, Lincoln University College, Kuala Lumpur, Malaysia. Electronic address: bapi@lincoln.edu.my.Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India; Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Malaysia.National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Department of Pharmaceutics, Opposite Air Force Station Palaj-Basan Road, Gandhinagar, Gujarat 382355, 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)

Comparative Study
Journal Article

Language

eng

PubMed ID

27815174

Citation

Gorain, Bapi, et al. "Comparative Biodistribution and Safety Profiling of Olmesartan Medoxomil Oil-in-water Oral Nanoemulsion." Regulatory Toxicology and Pharmacology : RTP, vol. 82, 2016, pp. 20-31.
Gorain B, Choudhury H, Tekade RK, et al. Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion. Regul Toxicol Pharmacol. 2016;82:20-31.
Gorain, B., Choudhury, H., Tekade, R. K., Karan, S., Jaisankar, P., & Pal, T. K. (2016). Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion. Regulatory Toxicology and Pharmacology : RTP, 82, 20-31. https://doi.org/10.1016/j.yrtph.2016.10.020
Gorain B, et al. Comparative Biodistribution and Safety Profiling of Olmesartan Medoxomil Oil-in-water Oral Nanoemulsion. Regul Toxicol Pharmacol. 2016;82:20-31. PubMed PMID: 27815174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion. AU - Gorain,Bapi, AU - Choudhury,Hira, AU - Tekade,Rakesh Kumar, AU - Karan,Saumen, AU - Jaisankar,P, AU - Pal,Tapan Kumar, Y1 - 2016/11/01/ PY - 2016/09/04/received PY - 2016/10/28/revised PY - 2016/10/28/accepted PY - 2016/11/7/pubmed PY - 2017/3/17/medline PY - 2016/11/6/entrez KW - Brain penetration KW - Hematological parameters KW - Histopathological characteristics KW - Olmesartan nanoemulsion KW - Sub-chronic toxicity KW - Tissue distribution SP - 20 EP - 31 JF - Regulatory toxicology and pharmacology : RTP JO - Regul Toxicol Pharmacol VL - 82 N2 - Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients. SN - 1096-0295 UR - https://www.unboundmedicine.com/medline/citation/27815174/Comparative_biodistribution_and_safety_profiling_of_olmesartan_medoxomil_oil_in_water_oral_nanoemulsion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0273-2300(16)30309-9 DB - PRIME DP - Unbound Medicine ER -