On the non-Gaussian distribution of human skin permeabilities

In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation.

Section: Permeation Studysupporting

confidence: 75%

Effect of Penetration Modifiers on the Dermal and Transdermal Delivery of Drugs and Cosmetic Active Ingredients

Otto

Wiechers²,

Kelly

et al. 2008

“…The permeation parameters were compared through a non-parametric statistical assay (Kruskal-Wallis Z; p ! 0.05) [18] .…”

Section: Skin Penetrationmentioning

confidence: 99%

A Study on the Influence of Emulsion Droplet Size on the Skin Penetration of Tetracaine

Izquierdo

Wiechers²,

Escribano³

et al. 2007

Objectives/Aims: The influence of emulsion droplet size on the skin penetration of a model drug, tetracaine, was studied. For this purpose, in vitro dermal and transdermal delivery of tetracaine from 6 emulsions (3 macro-emulsions with droplet sizes >1 µm and 3 nano-emulsions with droplet sizes <100 nm) were tested. Methods: Two approaches were used: in the first one, the composition of the emulsions was kept constant, while in the second one, the surfactant concentration in the aqueous phase was kept constant by varying the overall surfactant concentration. Results: The results from emulsions differing only in droplet size did not provide statistically significant evidence for the anticipated increase in transdermal or dermal delivery (after 24 h) when reducing emulsion droplet size. The same results were obtained when the surfactant concentration in the aqueous phase was kept constant, indicating that there is no influence of emulsion droplet size on the skin penetration of tetracaine within the droplet size range studied. Conclusion: This is in contrast to what has been reported in various publications that claim penetration to increase with reducing droplet size. It should be noted that the results reported so far are based on emulsions that apart from droplet size also differed in composition and/or system components.

“…The permeation parameters were compared through a non-parametric statistical assay (Kruskall-Wallis Z, p ! 0.05) [20] .…”

Section: Statisticsmentioning

confidence: 99%

Rapid Human Skin Permeation and Topical Anaesthetic Activity of a New Amethocaine Microemulsion

Escribano

Obach²,

Arévalo³

et al. 2005

We developed a fast-acting, topical, 4% (w/w) amethocaine microemulsion and tested its in vitro permeation in isolated human skin. Comparison with a commercial amethocaine gel (Ametop^® ) was performed using Franz diffusion cells. Permeability coefficient (k_p), flux (J) and percentage permeation after 10 h of microemulsion application were, in all cases, 1.5 times higher than those of the gel. The values obtained for the P₁ parameter [1], 1.06·10^–2 cm (microemulsion) and 0.724·10^–2 cm (gel) indicate that the microemulsion excipients favour amethocaine deposition in the skin, increasing the permeability coefficient, amount of drug retained in the skin, and the flux achieved. Analgesic activity was also examined in rats made hyperalgesic or allodynic after carrageenan-induced inflammation. The rats were distributed into four groups (n = 5–9 per group), each group receiving topically either amethocaine microemulsion, amethocaine gel (Ametop), amethocaine subcutaneous infiltration or nothing (controls). In edematous paws, anti-hyperalgesic activity appeared at 4.2 and 13.8 min after application of amethocaine microemulsion and gel, respectively. These effects are lower than after 0.5% w/w amethocaine infiltration. Amethocaine microemulsion was the only topical formulation with an anti-allodynic effect, although this effect was less than with amethocaine infiltration. These results suggest that microemulsion could be a valuable formula for improving amethocaine permeation and thus bringing rapid pain relief.