THE EFFECTS OF PHOSPHOLIPIDS ON THE PERCUTANEOUS PENETRATION OF INDOMETHACIN THROUGH THE DORSAL SKIN OF GUINEA-PIG IN-VITRO .2. THE EFFECTSOF THE HYDROPHOBIC GROUP IN PHOSPHOLIPIDS AND A COMPARISON WITH GENERAL ENHANCERS

The enhancing effects of phospholipids on the in vitro percutaneous pe netration of indomethacin (IM) was investigated using a dorsal skin of guinea pigs mounted on a Franz-type diffusion chamber. The phospholip ids were (1) six phosphatidylglycerol (PG) derivatives comprising PGE (from egg yolk), PGS (from soybean), DMPG (dimyristyl PG), DPPG (dipal mityl PG), DSPG (distearyl PG) and DOPG (dioleoyl PG); (2) five phosph atidylcholine (PC) derivatives comprising PCS (from soybean), PLE (fro m egg yolk), DOPC (dioleoyl PC), DLPC (dilinoleoyl PC) and HPC (hydrog enated PC, from soybean); (3) two phosphatidylethanolamine (PE) deriva tives comprising PE (from egg yolk) and DOPE (dioleoyl PE). The enhanc ing effects of PG derivatives on the percutaneous penetration of IM we re in the order of DOPG > PGE > PGS > DMPG > control > DPPG = DSPG. Th e 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 > con trol. The enhancement of percutaneous penetration of IM by atone, olei c acid (Delta 9, C18:F1), asclepic acid (Delta 11, C18: F1), and palmi toleic acid (Delta 9, C16:F1), which are known to be penetration enhan cers, were compared with that of phospholipids. DOPG, PGE, DOPC, DLPC and PCS showed significantly superior effects to these three unsaturat ed fatty acids on the percutaneous penetration of IM. Moreover, PGE, P GS, DOPG, PLE, PCS, DOPC, DLPC, PE and DOPE were better than atone on enhancing percutaneous penetration of IM. Differences in enhancement b y 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 unsatu rated 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.