Topical absorption of methotrexate: role of dermal transport

The treatment of psoriasis vulgaris: 1% topical methotrexate gel

“…For topical drugs used in psoriasis, the site of action is in the stratum spinosum and stratum germinativum 20 . Methotrexate is a water‐soluble drug.…”

“…[12][13][14][16][17][18][19] For topical drugs used in psoriasis, the site of action is in the stratum spinosum and stratum germinativum. 20 Methotrexate is a water-soluble drug. Its high molecular weight and dissolution at physiologic pH limit its capacity for passive diffusion.…”

“…21 Nevertheless, it has been shown that water-miscible ointment bases increase the rate of penetration through the stratum corneum. 20 Therefore, formulations prepared using various vehicles in water-miscible bases of methotrexate have been used locally in the treatment of psoriasis. [12][13][14]19 ESI, erythema, scale, and infiltration.…”

Skin Structure and Physiology

“…Thus, a number of studies have shown that both ionised and unionised molecules can penetrate a lipophilic membrane, although the rates of transport and routes taken are significantly different for both species (Barker and Hadgraft 1981;Swarbrick et al 1984;Siddiqui et al 1985). For example, ionised compounds have been shown to penetrate the skin by mechanisms of either ionpairing (Barker and Hadgraft 1981;Siddiqui et al 1985;Green and Hadgraft 1987;Oakely and Swarbrick 1987) or ion-exchange (Siddiqui et al1985(Siddiqui et al , 1987. Thus, the ionisation state of a potential penetrant, in the context of its pK a and the vehicle pH, will significantly affect the permeability of a molecule into and across the skin (Woolfson and McCafferty 1993a, b;Woolfson et al 1998;Moss et al 2006).…”

Analysing the Skin Barrier from Down Under

“…Using an experimental apparatus similar to that used for subcutaneous absorption by Levy and Rowland [25] in 1974, Siddiqui et al applied aqueous solutions of methotrexate [26] or steroids [27] directly to the exposed dermis of anaesthetized or sacrificed rats. Dermal transport was estimated by measuring the rate of disappearance of the solute from the donor solution applied to the dermis.…”