Influence of Ethanol on the Solubility, Ionization and Permeation Characteristics of Ibuprofen in Silicone and Human Skin

Abstract

In the context of topical and transdermal delivery, cosolvents may be expected to enhance solubility, modify drug partitioning behaviour and alter skin barrier properties. In the present study, we have investigated systematically the influence of increasing amounts of the cosolvent ethanol on the solubility, ionization, and permeability characteristics of ibuprofen in silicone and in skin. The possibility of ibuprofen self-association was also examined. As the amount of ethanol was raised from 0 to 100%, ibuprofen solubility was enhanced 5,500-fold relative to its aqueous solubility. Up to 50%, the pK_a of ibuprofen shifted from 4.44 to 5.68. Infrared spectroscopy confirmed the presence of ibuprofen in both monomer and dimer forms in vehicles containing 75 and 100% ethanol. In silicone membranes, the flux of ibuprofen increased 8-fold over the range of ethanol concentrations studied (0–100%) relative to aqueous solutions, with the highest flux observed for 100% ethanol. However, in skin, the flux of ibuprofen was optimal for 50:50 and 75:25 ethanol-water vehicles (>10-fold flux enhancement). The lower ibuprofen flux from pure ethanol may reflect the alcohol’s ability to dehydrate human skin. In general, the flux data confirm that increasing ethanol content enhances the solubility of ibuprofen in silicone and human skin as well as in the vehicle itself.

Development of ibuprofen-loaded nanostructured lipid carrier-based gels: characterization and investigation of in vitro and in vivo penetration through the skin

“…6,7 The characteristics of the permeation of IBU through the human skin have been reported by a number of research groups. [8][9][10][11][12][13] Earlier studies revealed that the topical therapeutic effectiveness of a drug is a function both of its penetration through the skin and of its potency. 7 IBU is less potent than diclofenac, for example, but the higher flux of IBU through the skin means that it is a better candidate for topical delivery, although it is still difficult to achieve its effective permeation by transdermal delivery.…”

Solubility of Acetaminophen and Ibuprofen in the Mixtures of Polyethylene Glycol 200 or 400 with Ethanol and Water and the Density of Solute-Free Mixed Solvents at 298.2 K

“…In addition to enhancing the aqueous solubility of drugs, cosolvents can alter other drug properties such as chemical stability 2 and skin permeability. 3 In a detailed report, the effects of ethanol concentration on the solubility, ionization, and permeability characteristics of ibuprofen were investigated. Experimental measurements showed that the diffusion of ibuprofen from ethanol + water mixtures across human skin is increased initially by increasing the ethanol concentration, reaches a maximum value, and then decreases with the further addition of ethanol, due to the dehydration effect of ethanol on stratum corneum.…”

“…Experimental measurements showed that the diffusion of ibuprofen from ethanol + water mixtures across human skin is increased initially by increasing the ethanol concentration, reaches a maximum value, and then decreases with the further addition of ethanol, due to the dehydration effect of ethanol on stratum corneum. 3 Ethanol is one of the most important and common cosolvents in the pharmaceutical industry and is used in many commercially available oral, parenteral, and soft gelatin formulations. 1 Polyethylene glycols (PEGs) are neutral polyethers which are freely soluble in water due to strong hydrogen-bonding with water molecules.…”

Skin Irritation Caused by Alcohol-Based Hand Rubs

“…For example, the enhancement ability of ethanol is maximized at the concentration of 50-70% (Kim et al, 1996;Watkinson et al, 2009). Hence the irritancy of antiseptic compounds may be amplified in alcohols-based hand rubs.…”