Enhancing effect of fumaric acid on transdermal penetration of loxoprofen sodium

Int J Pharm. 2020 Oct 15;588:119722. doi: 10.1016/j.ijpharm.2020.119722. Epub 2020 Aug 14.


Topical administration is a promising clinical strategy to avoid serious gastrointestinal adverse reactions of loxoprofen sodium (LOX), a new non-steroidal anti-inflammatory drug. Small molecule organic acids had been reported with the ability of promoting transdermal rate of several drugs. In this article, the effect of small molecule organic acids on the transdermal delivery of LOX was studied, and the possible mechanism was also explored by Fourier infrared spectroscopy, differential scanning calorimetry, tape stripping, etc. The results showed that lactic acid and fumaric acid could significantly increase the penetration rate of LOX and reduce time lag even without the help of acidic environment. The preliminary mechanism investigation inferred that fumaric acid could increase LOX's distribution in stratum corneum and might change its complexation state, but had little effect on the drug structure and skin's lipids and proteins configuration. The topical LOX gel using fumaric acid as penetration enhancer had higher transdermal rate, significant anti-inflammatory effect and no obvious skin irritation. This study proved the promising application of small molecule organic acids in transdermal enhancing and provided a potential strategy for transdermal delivery of LOX combined with fumaric acid.

Keywords: Loxoprofen sodium; Mechanism; Organic acids; Transdermal drug delivery.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Carrageenan
  • Disease Models, Animal
  • Female
  • Fumarates / pharmacology*
  • Gels
  • Inflammation / chemically induced
  • Inflammation / prevention & control*
  • Lactic Acid / pharmacology
  • Male
  • Phenylpropionates / administration & dosage*
  • Phenylpropionates / chemistry
  • Phenylpropionates / metabolism
  • Rabbits
  • Rats, Sprague-Dawley
  • Skin / drug effects*
  • Skin / metabolism
  • Skin Absorption / drug effects*
  • Swine
  • Swine, Miniature
  • Time Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Fumarates
  • Gels
  • Phenylpropionates
  • Lactic Acid
  • loxoprofen
  • fumaric acid
  • Carrageenan