Percutaneous absorption of haloperidol from different gel polymers through rabbit, human and hairless-mouse skins

ABSTRACT

Haloperidol is a butyrophenone derivative used for the treatment of psychotic symptoms. This compound is rapidly and almost completely absorbed when taken orally, but the oral bioavailability is about 60% due to extensive first-pass metabolism in the liver. Dorsal rabbit, human and hairless-mouse skins were used to investigate the diffusion properties of haloperidol. The transdermal permeation across full-thickness skins is reported from three polymer gel formulations was investigated using improved Franz-diffusion cells. Gels were prepared containing haloperidol and hydroxypropylmethyi cellulose [HPMC], carbopol 940 and polyethylene glycol mixture. Steady-state flux was rapidly achieved. Zero-order release of haloperidol from these formulations was observed. HPMC was concluded to be a suitable base for a matrix formulation. The reported partition coefficients in this study for human rabbit and hairless-mouse were 0.004, 0.041 and 0.155 respectively. The mechanism of action of the preparations tested were probably due to structural modification of the skin [stratum cornium] or fluidization of the cell contents in the epidermal layer