Surface recovery and stripping methods to quantify percutaneous absorption of caffeine in humans.

The percutaneous absorption of caffeine from two vehicles, an emulsion and an acetone solution, was quantified by in vivo techniques in humans. A surface recovery technique over a 6-h application and a stripping method after a 30-min application were performed on the volar aspect of the forearm on 12 volunteers. Caffeine was assessed by HPLC. Two phases were distinguished in the percutaneous absorption of caffeine: a higher filling up of the stratum corneum with the oil-in-water emulsion than with the acetone solution, which was then followed by a steady-state flux corresponding to the penetration in the living tissues. The permeability constants (Kp) with emulsion and acetone were 1.59 x 10(-4) and 9.53 x 10(-8) cm/h, respectively. The stripping method showed concentrations of caffeine in stratum corneum that were five times higher with emulsion (212 ng/cm2) than with acetone (37 ng/cm2). With acetone as a vehicle, approximately 40% of caffeine of the cornfield layer was found around the treated area. This sizeable lateral spread within the stratum corneum was not observed with the emulsion.

Effect of pressure on in vitro percutaneous absorption of caffeine.

The effect of increased pressure, which is a mechanical property of massage, was investigated on the percutaneous absorption of an amphiphilic compound (caffeine) in vitro on Franz diffusion cells, using excised human skin. 50 microliters of either a 320 micrograms/ml or a 15 mg/ml acetone solution of caffeine were pipetted onto the surface of each skin sample, which represented caffeine skin deposits of 5 micrograms/cm2 and 240 micrograms/cm2 respectively. During each experiment, a pressure device delivering 0.25 bar over the atmospheric pressure was applied for the first 30 min on half of the cells. At 2, 4, 6, 8, 12 and 24 h the aqueous dermal bathing solution, containing 14 g/l albumin, was removed and chromatographed. With the applied dose of 5 micrograms/cm2 no statistical difference was found between the cumulated absorbed amount under atmospheric pressure and increased pressure. On the other hand, with the applied dose of 240 micrograms/cm2, the permeation of caffeine was 1.8 times higher under increased pressure than the permeation under atmospheric pressure (p < 0.05). This enhancing effect of increased pressure was probably connected to either an improved transappendageal route during the percutaneous absorption process or a higher stratum corneum filling-up.