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A novel transdermal nanoethosomal gel of lercanidipine HCl for treatment of hypertension: optimization using Box-Benkhen design, in vitro and in vivo characterization

  • Heba F. Salem
  • Shahira F. El-Menshawe
  • Rasha A. KhallafEmail author
  • Yasmine K. Rabea
Original Article
  • 134 Downloads

Abstract

Poor bioavailability of drugs via oral route is the greatest challenge facing drug formulation. To overcome this obstacle, transdermal route was commonly used as an alternative route to improve bioavailability. Lercanidipine HCl (LER) is a vasoselective calcium-channel blocker that has a poor oral bioavailability of 10% due to its hepatic metabolism and low solubility. The main objective of this study was to develop nanoethosomal LER gel for transdermal delivery to increase its skin permeation and promote bioavailability. Nanoethosomes were prepared and optimized using a Box-Behnken design employing ethanol injection method. The design studied the influence of Phospholipon 90G (PL90G), LER, and ethanol concentrations on entrapment efficiency (EE%); vesicle size; % cumulative LER release (CLERR); and cumulative LER permeated per unit area at 24 h Q24 (μg/cm2). The pharmacokinetic parameters of the optimized formulation were determined in rats. Nanoethosomes showed a mean vesicle size between 210.87 and 400.57 nm and EE% ranging from 49.26 to 97.22%. The developed nanoethosomes enhanced % CLERR and Q24 values compared to drug suspension. The experimental parameters of optimized formulation were very close to those calculated by software. The pharmacokinetics study showed three times statistically significant (p < 0.05) enhancement in LER bioavailability following nanoethosomal LER gel transdermal application compared to that of oral LER suspension. Nanoethosomes can be considered as a promising carrier for LER transdermal delivery, thus will be fruitful therapy in hypertension management.

Graphical abstract

Keywords

Lercanidipine Hypertension Nanoethosomes Transdermal delivery Pharmacokinetics Gel 

Notes

Compliance with ethical standards

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13346_2019_676_MOESM1_ESM.docx (249 kb)
ESM 1 (DOCX 249 kb)

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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  • Heba F. Salem
    • 1
  • Shahira F. El-Menshawe
    • 1
  • Rasha A. Khallaf
    • 1
    Email author
  • Yasmine K. Rabea
    • 1
  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyBeni-Suef UniversityBeni SuefEgypt

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