ENHANCING EFFECT OF HYDROXYPROPYL-BETA-CYCLODEXTRIN ON CUTANEOUS PENETRATION ACTIVATION OF ETHYL 4-BIPHENYLYL ACETATE IN HAIRLESS MOUSE SKIN

The effect of hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) on the cut aneous penetration and activation of ethyl 4-biphenylyl acetate (EBA), a prodrug of non-steroidal anti-inflammatory drug 4-biphenylylacetic acid (BPAA), from hydrophilic ointment was investigated, using hairles s mouse skin in vitro. When the hydrophilic ointment containing a comp lex of EBA with HP-beta-CyD was applied to the full-thickness skin, HP -beta-CyD facilitated the penetration of EBA into the skin, the conver sion of EBA to BPAA in the epidermis and the transfer of BPAA to the r eceptor phase. Under the present condition, pre-and post-application o f the ointment containing HP-beta-CyD onto the skin did not affect the cutaneous penetration of EBA and its activation. When the ointment co ntaining the EBA:HP-beta-CyD complex was applied to the skin, the flux of BPAA through the tape-stripped skin was greater than that through the full-thickness skin, while the activation of the prodrug in the sk in was slowed down by the tape-stripping. When propylene glycol was us ed as a vehicle, HP-beta-CyD no longer enhanced the cutaneous permeati on of BPAA through the full-thickness skin. These results suggest that the enhancing effect of HP-beta-CyD on the cutaneous penetration of E BA would be ascribable largely to an increase in effective concentrati on of EBA in the ointment. Furthermore, the slow diffusion of EBA solu bilized in HP-beta-CyD through the stratum corneum, together with the vehicle effect, could make the prodrug more susceptible to the metabol ic process that is active in the epidermis, eventually leading to the facilitated activation of the prodrug. (C) 1998 Elsevier Science B.V.