Possibilities of the microemulsion use as indomethacin solubilizer and its effect on in vitro and ex vivo drug permeation from dermal gels in comparison with transcutol®

Drug Dev Ind Pharm. 2020 Sep;46(9):1468-1476. doi: 10.1080/03639045.2020.1802483. Epub 2020 Aug 7.

Abstract

Objective: Transcutol® is a perfect solubilizer and an effective permeation enhancer of many active substances commonly used in cosmetics. Microemulsions due to the content of surfactant and co-surfactant could be also considered as chemical permeation enhancers that may support transdermal delivery of poorly water- soluble drugs. The purpose of this study was to investigate the effect of Transcutol® and potential microemulsions on diffusion of poorly soluble indomethacin through an artificial membrane and excised rat skin.

Methods: After drug solubilization in different enhancers, drug was dispersed in sodium alginate or carbopol gel used as dermal basis. For characterization of the microemulsions, the basic physico-chemical properties were determined. In vitro as well as ex vivo drug release was determined by vertical Franz cells.

Results: Enhancing effect of the examined microemulsions was observed only in carbopol gel. There was an increase in cumulative drug amount released through synthetic membrane by 37.7-39.8% from the microemulsion formulation and 90.6% from Transcutol® formulation within 6 h compared to the control samples. The differences between the permeation curves with or without the content of the enhancers were statistically significant (p < .05). Pearson correlation coefficients indicate a very high degree of dependence (r > 0.9) between in vitro and ex vivo drug release from all dermal vehicles used.

Conclusion: It can be stated that Transcutol® is the best solubilizer and also penetration enhancer from the examined, and therefore it seems to be effective excipient/solubilizer in topical IND formulation.

Keywords: Microemulsion; Transcutol®; chemical enhancer of penetration; indomethacin; skin permeation; solubilization.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Ethylene Glycols / chemistry*
  • Gels / chemistry
  • Gels / metabolism
  • Indomethacin*
  • Rats
  • Skin / metabolism
  • Skin Absorption*

Substances

  • Ethylene Glycols
  • Gels
  • carbitol
  • Indomethacin