Enhanced Oral Bioavailability of Felodipine from Solid Lipid Nanoparticles Prepared Through Effervescent Dispersion Technique

Abstract

Felodipine (FLD), a dihydropyridine calcium channel blocker with excellent antihypertensive effect, is poorly soluble and undergoes extensive hepatic metabolism, which lead to poor oral bioavailability (about 15%) and limit its clinic application. The goal of this study was to develop solid lipid nanoparticles (SLNs) loading FLD to improve the oral bioavailability. The FLD loaded solid lipid nanoparticles (FLD-SLNs) were prepared by the effervescent dispersion technique developed by our laboratory, which might have some advantages over traditional methods. The FLD-SLNs showed desired particle characteristics with particle size (198.15 ± 1.82 nm), poly dispersity index (0.26 ± 0.02), zeta-potential (− 25.53 ± 0.60 mV), entrapment efficiency (95.65 ± 0.70%), drug loading (2.33 ± 0.10%), and a spherical appearance. Pharmacokinetic results showed that the FLD-SLNs presented 3.17-fold increase in area under the curve (AUC(0-t)) compared with free FLD after oral administration in beagle dogs, which indicated that SLNs prepared using the effervescent dispersion technique can improve the bioavailability of lipophilic drugs like felodipine by enhancement of absorption and reduction first-pass metabolism.

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Acknowledgments

This study was financially supported by the Science and Technology Fund for Distinguished Young Scholars of Sichuan Province (No.2017JQ0013) and Basic Research (No.2016JY0192), the Joint Fund of Luzhou City and Southwest Medical University (No.2017LZXNYD-T02), the scientific research Foundation of the Education Department of Sichuan Province (No.17ZA0439, 18ZB0646), and the scientific research Foundation of Southwest Medical University (No.2016-63).

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Correspondence to Ling Zhao or Yumeng Wei.

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The animal studies were approved by the Committee on the Ethics of Animal Experiments of the Southwest Medical University (No 2015DW040).

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He, Y., Zhan, C., Pi, C. et al. Enhanced Oral Bioavailability of Felodipine from Solid Lipid Nanoparticles Prepared Through Effervescent Dispersion Technique. AAPS PharmSciTech 21, 170 (2020). https://doi.org/10.1208/s12249-020-01711-2

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KEY WORDS

  • effervescent dispersion technique
  • felodipine
  • oral bioavailability
  • solid lipid nanoparticles