The effects of phospholipids on the percutaneous penetration of indomethacin through the dorsal skin of guinea pig in vitro. 2. The effects of the hydrophobic group in phospholipids and a comparison with general enhancers

Abstract

The enhancing effects of phospholipids on the in vitro percutaneous penetration of indomethacin (IM) was investigated using a dorsal skin of guinea pigs mounted on a Franz-type diffusion chamber. The phospholipids were (1) six phosphatidylglycerol (PG) derivatives comprising PGE (from egg yolk), PGS (from soybean), DMPG (dimyristyl PG), DPPG (dipalmityl PG), DSPG (distearyl PG) and DOPG (dioleoyl PG); (2) five phosphatidylcholine (PC) derivatives comprising PCS (from soybean), PLE (from egg yolk), DOPC (dioleoyl PC), DLPC (dilinoleoyl PC) and HPC (hydrogenated PC, from soybean); (3) two phosphatidylethanolamine (PE) derivatives comprising PE (from egg yolk) and DOPE (dioleoyl PE). The enhancing effects of PG derivatives on the percutaneous penetration of IM were in the order of DOPG > PGE > PGS > DMPG > control > DPPG = DSPG. The enhancing effects of PC derivatives on the percutaneous penetration of IM were in the order of DOPC > DLPC > PCS > PLE > control > HPC and the effects of PE derivatives on the penetration were DOPE > PE > control. The enhancement of percutaneous penetration of IM by azone, oleic acid (Δ9, C18:F1), asclepic acid (Δll, C18: F1), and palmitoleic acid (Δ9, C16:F1), which are known to be penetration enhancers, were compared with that of phospholipids. DOPG, PGE, DOPC, DLPC and PCS showed significantly superior effects to these three unsaturated fatty acids on the percutaneous penetration of IM. Moreover, PGE, PGS, DOPG, PLE, PCS, DOPC, DLPC, PE and DOPE were better than azone on enhancing percutaneous penetration of IM. Differences in enhancement by phospholipids may be due to differences in hydrophobic groups rather like the effects of hydrophilic groups shown in a previous study. It was observed that hydrophobic groups in phospholipids had to be unsaturated fatty acids in order to promote percutaneous penetration of IM. These results suggest that phospholipids containing unsaturated fatty acids in the hydrophobic group are strong penetration enhancers of the percutaneous delivery of some topically-applied drugs.