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Effect of penetration enhancers and amorphization on transdermal permeation flux of raloxifene-encapsulated solid lipid nanoparticles: an ex vivo study on human skin

  • Krishna Kumar Patel
  • Shilpkala Gade
  • Md. Meraj Anjum
  • Sanjay Kumar Singh
  • Pralay Maiti
  • Ashish Kumar Agrawal
  • Sanjay SinghEmail author
Original Article
  • 3 Downloads

Abstract

Despite 60% oral absorption, high first-pass metabolisms resulted in 2% oral bioavailability of raloxifene and also suffer poor water solubility. In this study, we developed the penetration enhancer rich hydrogel containing raloxifene-loaded solid lipid nanoparticles (RL-SLNs) for transdermal route. Interestingly, SLN offers higher solubility and thermodynamic activity due to amorphization of drug and evasion of first-pass metabolism by transdermal route. Cumulative effect will contribute to enhanced permeation flux, controlled drug release and enhanced bioavailability. Nanoparticles were synthesized using solvent emulsification–evaporation method and evaluated further for various physicochemical properties, ex vivo permeation and hydration studies. RL-SLN3 with particle size 227.9 ± 12.6 nm, polydispersity index 0.283 ± 0.021, zeta potential 15.4 ± 1.7 mV and entrapment efficiency 77.04 ± 5.08% was selected for further studies as optimized formulation. Differential scanning calorimetric method revealed that 54.75% of RL had changed to amorphous state adding to enhanced solubility. Furthermore, the results of ex vivo permeation studies on human skin elucidated that 10% d-limonene in combination with RL-SLN had excellent permeation flux (7.24 ± 0.49 µg/cm2 h) compared to RL-SLN alone and other penetration enhancers tested. Thus, the output of above studies suggested that transdermal delivery of RL-SLN using d-limonene as penetration enhancer can be a promising approach to evade the first-pass metabolism and increase the systemic bioavailability of RL.

Keywords

Raloxifene SLN Skin permeation Penetration enhancer Hydrogel Ex vivo 

Notes

Acknowledgements

The author Prof. Sanjay Singh heartily acknowledges Indian Institute of Technology, (BHU), Varanasi, for supporting the research work in terms of research support grant. The author also acknowledges Prof. O.N. Srivastava (Emeritus Professor), Department of Physics, Institute of Science, Banaras Hindu University, for extending the X-ray diffraction facility to carry out my research study.

Compliance with ethical standards

Conflict of interest

There is no financial conflict of interest.

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Copyright information

© King Abdulaziz City for Science and Technology 2019

Authors and Affiliations

  • Krishna Kumar Patel
    • 1
  • Shilpkala Gade
    • 1
  • Md. Meraj Anjum
    • 1
  • Sanjay Kumar Singh
    • 1
  • Pralay Maiti
    • 2
  • Ashish Kumar Agrawal
    • 1
  • Sanjay Singh
    • 1
    Email author
  1. 1.Department of Pharmaceutical Engineering and TechnologyIIT (BHU)VaranasiIndia
  2. 2.School of Materials Science and TechnologyIIT (BHU)VaranasiIndia

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