Quantitative Evaluation of Aqueous Isopropyl Alcohol Enhancement on Skin Flux of Terbutaline (Sulfate). 2. Permeability Contributions of Equilibrated Drug Species across Human Skin in Vitro

Abstract

This paper demonstrates the usefulness of an equilibria-cotransport model for understanding the isopropyl alcohol-enhanced transport of an ionizable model compound, terbutaline in its sulfate salt form, through human skin in vitro. With the same isopropyl alcohol concentrations (0 - 80% v/v) present at both sides of skin, the permeation experiments were conducted using split-thickness skin and dermis membranes. The equilibria-cotransport model was consistent with total terbutaline flux and a terbutaline-to-sulfate flux ratio, both increased with increasing isopropyl alcohol and/or terbutaline sulfate concentrations. From the saturated drug solutions, aqueous isopropyl alcohol enhanced terbutaline skin flux about 10 - 100-fold with the maximum at 60 - 80% isopropyl alcohol. This overall flux enhancement was qualitatively separated into the contributions of isopropyl alcohol effects on both equilibrated donor concentrations and skin permeabilities of protonated terbutaline, terbutaline-sulfate ion pair anion, and neutral terbutaline-sulfate (2:1) ion triplet. In addition to altering the species equilibria, isopropyl alcohol was found to enhance the transport of both neutral and ionic species of terbutaline sulfate across stratum corneum.

Effects of Isopropanol–Isopropyl Myristate Binary Enhancers on In Vitro Transport of Estradiol in Human Epidermis: A Mechanistic Evaluation

“…For several drugs, the flux across skin was observed to be empirically linear with that of ethanol 8, 9. Another polar enhancer, isopropanol (IPA) enhanced the transport of both neutral and ionic species across stratum corneum 10. A nonpolar enhancer, isopropyl myristate (IPM), is well tolerated topically in many pharmaceutical and cosmetic preparations 11.…”

Intracellular or Intercellular Localization of the Polar Pathway of Penetration Across Stratum Corneum

“…[1][2][3][4][5][6][7][8] The latter one consists of aqueous micropores or microchannels. The hydrophilic pores have been indicated as the site of penetration for mannitol, 1,6,7,9 urea, 1 vidarabine, 7 glycols, sucrose, 4 antipyrine, 2,4 cephalexin, 11 phenylalanine, baclofen, benazeprilat, libenzapril, 8 tetraethylammonium, 1,7 salicylate, 10 morphine, 5 and terbutaline 12 ions. However, to date, the model is not universally accepted because of insufficient identification and characterization of the pores.…”

Lidocaine permeation from a lidocaine NaCMC/gel microgel formulation in microneedle-pierced skin: vertical (depth averaged) and horizontal permeation profiles

“…The dermis layer skin thickness can vary from 200 to 350μm [52]. However, there is no distinct, fast procedure for VE and dermis layer boundary identification, followed by micro dissection according to fundamental histological changes in strata.…”