IN-VITRO PERMEABILITY OF THE HUMAN NAIL AND OF A KERATIN MEMBRANE FROM BOVINE HOOVES - PENETRATION OF CHLORAMPHENICOL FROM LIPOPHILIC VEHICLES AND A NAIL LACQUER

Lipophilic vehicles and especially nail lacquers are more appropriate for topical application on the nail than aqueous systems because of th eir better adhesion. This work has, therefore, studied the penetration through the human nail plate of the model compound chloramphenicol fr om the lipophilic vehicles medium chain triglycerides and n-octanol an d from a lacquer based on quaternary poly(methyl methacrylates) (Eudra git RL). The results were compared with data obtained with a keratin m embrane from bovine hooves. If the swelling of the nail plate or the h oof membrane is not altered by use of lipophilic vehicles, the maximum flux of the drug is independent of its solubility in the vehicle and is the same as that from a saturated aqueous solution. These vehicles are not able to enter the hydrophilic keratin membrane because of thei r nonpolar character and so cannot change the solubility of the penetr ating substance in the barrier. If the concentration of the drug in th e nail lacquer is sufficiently high, the maximum flux through both bar riers equals that from aqueous vehicles or even exceeds it because of the formation of a supersaturated system. Penetration through the nail plate follows first order kinetics after a lag-time of 400 h. The cou rse of penetration through the hoof membrane is initially membrane-con trolled and later becomes a matrix-controlled process because of the m embrane's greater permeability. Chloramphenicol is dissolved in the la cquer up to a concentration of 31%. The relative release rates from th ese solution matrices are independent of the drug concentration but th ey decrease on changing to a suspension matrix. These results show tha t drug flux is independent of the character of the vehicle and that pe netration of the drug is initially membrane-controlled and changes to being matrix-controlled as the drug content of the lacquer decreases.