Effect of ion-pairing and enhancers on scutellarin skin permeability.
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.
Wang
Manli
M
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
Fang
Liang
L
Ren
Changshun
C
Li
Ting
T
D000279:Administration, Cutaneous; D000588:Amines / Q000737:chemistry*; D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000493:pharmacokinetics*; D001381:Azepines / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000737:chemistry; D005965:Glucuronates / Q000737:chemistry / Q000493:pharmacokinetics*; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008610:Menthol / Q000737:chemistry; D009226:Myristates / Q000737:chemistry; D019301:Oleic Acid / Q000737:chemistry; D010539:Permeability; D010592:Pharmaceutic Aids / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D012995:Solubility
D000588:Amines; D001381:Azepines; D005965:Glucuronates; D007477:Ions; D009226:Myristates; D010592:Pharmaceutic Aids; D011760:Pyrrolidinones; C008205:isopropyl myristate; D008610:Menthol; C484876:scutellarin; C035229:laurocapram; D019301:Oleic Acid; D000431:Ethanol; D047310:Apigenin; C038678:N-methylpyrrolidone