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

Abstract

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 [<citeref rid="ref001">1</citeref>], 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.

Novel isotretinoin microemulsion-based gel for targeted topical therapy of acne: formulation consideration, skin retention and skin irritation studies

“…8a-d. Draize patch test is a reliable method and the results obtained from this study can be linked to those obtained in humans (Biruss and Valenta 2008;Kantarci et al 2007;Escribano et al 2005). The skin irritation studies indicated that MBG containing ITTN resulted in less irritation as compared to marketed ITTN formulation (Sotret Ò gel) after 72 h of application (Table 6).…”

“…This phenomenon has been hypothesized in some investigations (Biruss and Valenta 2008;Kantarci et al 2007;Escribano et al 2005). Though the flux value of ITTN-based gel (0.0265 ± 0.0017 lg/cm 2 /h) is lesser than marketed ITTN gel (0.0284 ± 0.0047 lg/cm 2 / h), the difference is not significant (P [ 0.05).…”

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“…Finally, Tween -80 and propylene glycol were selected as an ideal surfactant and co-surfactant for the system. [15][16] Optical transparency: Optical transparency of the formulation was determined by inspecting the sample in clear and transparent container under the presence of good light against reflection into the eyes, and viewed against black and white illuminated background.…”

Application of Microemulsions in Dermal and Transdermal Drug Delivery

“…Using human skin, Escribano et al have shown that 4% amethocaine microemulsions prepared with decane, water and lauromacrogol 300, produced a 1.5-fold higher flux and permeability coefficient value than commercially available gels [92] . The same authors suggested that these microemulsions promoted the skin deposition and flux of amethocaine via enhanced partitioning into the skin rather than by increasing their diffusivity in skin.…”