Development of olmesartan medoxomil optimized nanosuspension using Box-Behnken design to improve oral bioavailability.

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Development of olmesartan medoxomil optimized nanosuspension using Box-Behnken design to improve oral bioavailability.

Drug Dev Ind Pharm. 2017 Mar 08;:1-29

Authors: K N, D N, V K

Abstract
The aim of present investigation was to enhance the oral bioavailability of olmesartan medoxomil by improving its solubility and dissolution rate by preparing nanosuspension (OM-NS), using Box-Behnken design. In this, four factors were evaluated at three levels. Independent variables include: concentration of drug (X1), concentration of surfactant (X2), concentration of polymer (X3) and number of homogenization cycles (X4). Based on preliminary studies the size (Y1), zeta potential (Y2) and % drug release at 5min (Y3) were chosen as dependent responses. OM-NS were prepared by high pressure homogenization method. The size, PDI, Zeta potential (ZP), assay, in vitro release and morphology of OM-NS were characterized. Further, the pharmacokinetic behaviour of OM-NS was evaluated in male Wistar rats. Statistically optimized OM-NS formulation exhibited mean particle size of 492 nm, ZP of -27.9 mV and 99.29% release in 5 min. OM-NS showed more than 4 times increase in its solubility than pure OM. DSC and XRD analyses indicated that the drug incorporated into OM-NS was in amorphous form. The morphology of OM-NS was found to be nearly spherical with high dispersity by scanning electron microscopic studies. The pharmacokinetic results showed that OM lyophilized nanosuspension exhibited improved pharmacokinetic properties compared to coarse powder suspension and marketed tablet powder suspension. Oral bioavailability of lyophilized nanosuspension was increased by 2.45 and 2.25 folds compared to marketed tablet powder suspension and coarse powder suspension, respectively. Results of this study lead to conclusion that nanosuspension approach was effective in preparing OM formulations with enhanced dissolution and improved oral bioavailability.

PMID: 28271908 [PubMed - as supplied by publisher]

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