Title:Development, Characterization and In vivo Pharmacokinetic Studies of
Olmesartan Medoxomil Nanosuspension for the Effective Treatment of
Hypertension
Volume: 12
Issue: 5
Author(s): Udit Narayan Singh, Bhargav E*, Haranath C, Chitra Sekhar C, Charitha B and MV Jyothi
Affiliation:
- RERDS-CPR, Raghavendra Institute of Pharmaceutical Education and Research, Anantapuramu -
515721, India
Keywords:
Olmesartan, medoxomil, nanosuspension, 2III3-1fractional factorial, design, oral bioavailability.
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.
