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Formulation, optimization, and in vitro–in vivo evaluation of olmesartan medoxomil nanocrystals

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Abstract

The aim of the present study is to increase the saturation solubility and oral bioavailability of olmesartan medoxomil (OLM) using nano-sized crystals produced using a combination of antisolvent precipitation and high-shear homogenization. A response surface design comprising 46 runs was used to optimize the OLM nanocrystal formulation. The optimized formulation was produced using a combination of d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) (0.7% w/v), Pluronic F-68® (0.5% w/v), and drug concentration (0.2% w/v) and subjected to 10 and 15 homogenization cycles at 1000 and 1700 bar, respectively. The particle size, polydispersity index (PDI), and zeta potential of optimized formulation were found to be 140 ± 10.34 nm, 0.07 ± 0.016, and −21.43 ± 2.33 mV, respectively. The optimized formulation exhibited irregular morphology as evaluated by scanning electron microscopy and was crystalline as determined by thermal analysis and powder X-ray diffraction studies. OLM nanocrystals showed a marked increase in the saturation solubility as well as rapid dissolution rate in comparison with the pure drug. No significant change in the particle size, PDI, and zeta potential was observed when optimized formulation was stored at room and refrigeration conditions for 3 months. Lastly, in vivo pharmacokinetic studies in Sprague-Dawley rats substantiate the ability of OLM nanocrystal formulation to significantly improve (∼4.6-fold) the oral bioavailability of OLM in comparison with the free drug. This study has established a potential and commercial viable OLM formulation with enhanced saturation solubility and in vivo oral bioavailability.

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Acknowledgements

The authors are thankful to the director, NIPER, for providing necessary infrastructure facilities. The authors also thank Rahul R. Mahajan for providing technical assistance with scanning electron microscopy.

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Authors and Affiliations

  1. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S, Nagar, Punjab, 160062, India

    Sanyog Jain, Kamlesh Patel, Sumit Arora, Venkata Appa Reddy & Chander Parkash Dora

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  1. Sanyog Jain
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  2. Kamlesh Patel
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  3. Sumit Arora
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  4. Venkata Appa Reddy
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  5. Chander Parkash Dora
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Correspondence to Sanyog Jain.

Ethics declarations

All animal experiments were carried out under the guidelines compiled by the Committee for the Purpose of Control and Supervision of Experiments on Animals ((CPCSEA), Ministry of Environment, Forests and Climate Change, Govt. of India), and all the study protocols were duly approved by the Institutional Animal Ethics Committee of NIPER, S.A.S., India, before the start of the study

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The authors declare that they have no conflicts of interest.

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Jain, S., Patel, K., Arora, S. et al. Formulation, optimization, and in vitro–in vivo evaluation of olmesartan medoxomil nanocrystals. Drug Deliv. and Transl. Res. 7, 292–303 (2017). https://doi.org/10.1007/s13346-016-0355-2

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