Effect of phosphatidylcholine on skin permeation of indomethacin from gel prepared with liquid paraffin and hydrogenated phospholipid.
The effects of hydrogenated and unhydrogenated phosphatidylcholine (HPC, PC) on the permeation of indomethacin (IM) through hairless rat skin were investigated using liquid paraffin (LP) and a gel prepared with LP and hydrogenated soybean phospholipid (HSL). IM solubility at 95 degrees C increased in proportion to the concentration of HPC or PC, whereas solubility at 37 degrees C did not increase with HPC. IM showed no permeation until 10 h from LP without HPC/PC, but permeated at rates of approximately 5 and 10 microg/cm2 within 10 h from LP with HPC and PC, respectively. The permeation from the gel with various formulations (HSL, 15%; PC/HPC, 0-5%; IM, 0.5-2%) was determined. Permeation rates were 1.7-4.8 microg/cm2 per h and were proportional to the skin concentration. Skin concentration was correlated to the release rate from the gel. We concluded that IM was solubilized by phospholipids, high activity in the vehicle led to high partition of IM in skin, and permeation increased due to a high skin concentration.
Fujii
M
M
Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakeun, Machida, 194-8543, Tokyo, Japan. fujii@ac.shoyaku.ac.jp
Shiozawa
K
K
Watanabe
Y
Y
Matsumoto
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005782:Gels; D007213:Indomethacin / Q000493:pharmacokinetics*; D008297:Male; D008899:Mineral Oil; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010743:Phospholipids; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D010713:Phosphatidylcholines; D010743:Phospholipids; D008899:Mineral Oil; D007213:Indomethacin