Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion.
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.
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.
Bapi
B
Gorain
Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India; Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Malaysia.
Hira
H
Choudhury
National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Department of Pharmaceutics, Opposite Air Force Station Palaj-Basan Road, Gandhinagar, Gujarat 382355, India.
Rakesh Kumar
RK
Tekade
Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Saumen
S
Karan
Department of Chemistry, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
P
P
Jaisankar
Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India. Electronic address: proftkpal@gmail.com.
Tapan Kumar
TK
Pal
D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid; D004326:Drinking / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D004435:Eating / Q000187:drug effects; D004655:Emulsions; D008297:Male; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles; D009821:Oils / Q000737:chemistry*; D000068557:Olmesartan Medoxomil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D010539:Permeability; D017208:Rats, Wistar; D015203:Reproducibility of Results; D018570:Risk Assessment; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D059550:Toxicity Tests, Subchronic; D014867:Water / Q000737:chemistry*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D004337:Drug Carriers; D004655:Emulsions; D009821:Oils; D014867:Water; D000068557:Olmesartan Medoxomil
Brain penetration; Hematological parameters; Histopathological characteristics; Olmesartan nanoemulsion; Sub-chronic toxicity; Tissue distribution