Penetration enhancement by menthol combined with a solubilization effect in a mixed solvent system

Hsiu O. Ho, Ling Chun Chen, Hua Mei Lin, Ming Thau Sheu

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


The improvement in solubility of indomethacin due to the presence of menthol in various cosolvent systems consisting of water, alcohol and propylene glycol was examined by a mixture design in this study. A proper model to quantitatively describe the effect of menthol at different concentrations on the solubility of indomethacin was compared based on the statistical parameters provided by DESIGN-EXPERT. Then three cosolvent systems with the addition of menthol to solubilize indomethacin to extents of 1.0, 1.5 or 2.0% w/v were selected. The penetration of indomethacin through nude mouse skin from these three cosolvent systems with the addition of 0- 12% menthol was investigated and followed by a discussion on the penetration mechanism. The results showed that menthol was able to improve drug solubility to different extents for different cosolvent systems. Optimally, a cosolvent system with an equal ratio of the three solvents, water, alcohol and propylene glycol, showed the highest extent of improvement in the solubility at all concentrations of menthol. The enhancement factors for indomethacin penetration due to menthol in different cosolvent systems were compared, based either on the permeation coefficient (K(p)) or the separate overall effects on the skin (Flux). Both comparisons gave similar results. The influence of menthol was more significant compared to that of the cosolvent systems and the extent of this influence increased with an increase in the amount added, reaching a maximum at a specific amount of menthol for each different cosolvent system.

Original languageEnglish
Pages (from-to)301-311
Number of pages11
JournalJournal of Controlled Release
Issue number2-3
Publication statusPublished - Feb 12 1998


  • Enhancement
  • Indomethacin
  • Menthol
  • Penetration
  • Solubility

ASJC Scopus subject areas

  • Pharmaceutical Science


Dive into the research topics of 'Penetration enhancement by menthol combined with a solubilization effect in a mixed solvent system'. Together they form a unique fingerprint.

Cite this