Absolute Concentrations of Dithranol and Triacetyl-Dithranol in the Skin Layers After Local Treatment: In Vivo Investigations with Four Different Types of Pharmaceutical Vehicles

Abstract

The pharmacokinetics of dithranol (anthralin) and its triacetate were investigated by employing a method which determines the quantity of the drug that penetrated into single layers of the human skin in vivo. For this purpose, tritium-labeled dithranol or triacetyl-dithranol was incorporated into four different ointments. The ointments were applied to the skin and biopsies were taken after 10, 30, 100, and 1000 min. The horny layer was removed before biopsy by Scotch tape stripping. The biopsies were sliced horizontally and the tritium determined in each sample. Dithranol as well as its triacetate penetrated best from more hydropholic ointments (Vaseline and aqueous wool-wax-alcohol ointment). From hydrophilic ointments (polyethylene glycol ointment and aqueous hydrophilic cream), only poor penetration was observed. Dithranol penetrated in far greater amounts than its triacetate, and the two compounds revealed fundamentally different penetration kinetics in epidermis and dermis. The data indicate that the triacetate was not split into its parent compound, dithranol, in substantial quantity, as the data obtained show the criteria of two independent substances.

Delivery of drugs applied topically to the skin

“…The first studies using this technique were done in the early 1970s [112][113][114]. Flux may be increased as a result of a reduced SC thickness, or a penetrant may have direct access to the viable epidermis on complete elimination of the SC.…”

Dithranol: A Review of the Mechanism of Action in the Treatment of Psoriasis vulgaris

“…The penetration of dithranol through the epidermis is faster in a lipophilic than in a hydrophilic vehicle [24], The homy layer presents less of a barrier to dithranol than to other drugs when applied in a lipophilic oint ment [25]. Kammerau et al [24] studied the penetration of tritium-labelled dithranol into human skin in vivo.…”

“…Kammerau et al [24] studied the penetration of tritium-labelled dithranol into human skin in vivo. They found that 300 min after the application of 0.1% of dithranol in petrolatum, the absolute con centration of the drug in the epidermis was maximum (93.66 pM), and at this time the concentrations of dithranol in the stratum corneum and in the dermis were far lower (32.49 and 0.…”

Dithranol in an Emulsifying Oil Base (Bio-Wash-Oil) for the Treatment of Psoriasis of the Scalp

“…in a formulation using a cream base (Psoradrate ® ) [6,7]. One reason for the reluctant use of dithranol on the scalp may be that during in vitro examinations, slower release and penetration of the drug has been observed from a cream base [8]. A major obstacle to the development of improved formulations is, however, the basic instability of dithranol which on the skin degrades faster than can be detected by currently available analytical equipment [9].…”