Effect of ion-pairing and enhancers on scutellarin skin permeability

Abstract

The aim of this work was to investigate the effect of enhancers and organic amines on the in-vitro percutaneous absorption of the major pharmacologically active compound, scutellarin, obtained from breviscapine extract. The donor vehicle consisted of isopropyl myristate-ethanol in a ratio of 4:1. Percutaneous absorption across full thickness rat skin was investigated in-vitro using 2-chamber diffusion cells, with reverse-phase HPLC for quantification of the permeating scutellarin. Organic amines increased scutellarin permeation by ion-pair formation. We also found that the cumulative amount of scutellarin over a period of 12 h of scutellarin was inversely related to the molecular weight of organic amines (r = 0.9134), as well as the logarithm of scutellarin permeability coefficient inversely related to the partition coefficient of organic amines (r = 0.8929). All the permeation enhancers tested increased the cumulative amount of scutellarin over a period of 12 h, and the order of this increase was n-methyl-2-pyrrolidone, oleic acid, menthol or Azone. Drug solubility in donor phase was markedly increased by Azone and n-methyl-2-pyrrolidone, and reduced by menthol and oleic acid. The combined effects of ethanolamine plus Azone, ethanolamine plus menthol, and Azone plus menthol were also investigated. Azone plus menthol had a synergistic effect on the cumulative amount of scutellarin over a period of 12 h.