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Nanoscience & Nanotechnology-Asia

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ISSN (Print): 2210-6812
ISSN (Online): 2210-6820

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Research Article

Development, Characterization and In vivo Pharmacokinetic Studies of Olmesartan Medoxomil Nanosuspension for the Effective Treatment of Hypertension

Author(s): Udit Narayan Singh, Bhargav E*, Haranath C, Chitra Sekhar C, Charitha B and MV Jyothi

Volume 12, Issue 5, 2022

Published on: 01 November, 2022

Article ID: e181022210130 Pages: 12

DOI: 10.2174/2210681213666221018092035

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Abstract

Introduction: The present work aims to increase the saturation solubility and the bioavailability of Olmesartan medoxomil (OM) via an acid-base neutralization-based nanosuspension technique.

Methods: The initial screening studies revealed that changes in the concentration of HPMC E15 (100-200 mg), mechanical stirring speed (SS) (900-1200 rpm) and stirring time (ST) (60-120 min) affected the responses. Effects produced by the factors (HPMC E15, SS, and ST) on responses (particle size, PDI, and cumulative % drug release (%CDR)) were investigated using a 2III3-1 fractional factorial design with replicates and four midpoints. For the development of Olmesartan medoxomil nanosuspension, an acid-base neutralization technique was employed.

Results: Pareto chart, perturbation plots and ANOVA were used to identify significant factors. The pvalue <0.05 indicated the factors to be considered significant. The Particle size and PDI of all formulations ranged from 286.7 nm - 718.1 nm and 0.146 – 0.415, respectively. Drug release from all formulations ranged from74.0-103.7%. Pure drug solubility and optimized formula solubility were reported to be 108.6 g/ml and 1650.72 g/ml, respectively. Contour and 3D surface plots led to the identification of design space in which HPMC E15, SS and ST can be oriented at 148.8-151 mg, 959-1000 rpm and 106-120 min, respectively, to get particle size <500 nm, PDI <0.5 and % CDR >95%.SEM results indicated that the particles were nearly spherical.

Conclusion: In vivo pharmacokinetic studies conducted in Wistar rats exhibited ~4.7 folds enhancement in optimized OM nanosuspension oral bioavailability compared to pure drug. It can be concluded that the selected method and application of the design of the experimentation technique enhanced the saturation solubility and bioavailability of OM.

Graphical Abstract

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