Establishing the importance of oil-membrane interactions on the transmembrane diffusion of physicochemically diverse compounds

There has been considerable recent interest in employing computer models to investigate the relationship between the structure of a molecule and its dermal penetration. Molecular permeation across the epidermis has previously been demonstrated to be determined by a number of physicochemical properties, for example, the lipophilicity, molecular weight and hydrogen bonding ability of the permeant. However little attention has been paid to modeling the combined effects of permeant properties in tandem with the properties of vehicles used to deliver those permeants or to whether data obtained using synthetic membranes can be correlated with those obtained using human epidermis. This work uses Principal Components Analysis (PCA) to demonstrate that, for studies of the diffusion of three model permeants (caffeine, methyl paraben and butyl paraben) through synthetic membranes, it is the properties of the oily vehicle in which they are applied that dominated the rates of permeation and flux. Simple robust and predictive descriptor-based quantitative structure–permeability relationship (QSPR) models have been developed to support these findings by utilizing physicochemical descriptors of the oily vehicles to quantify the differences in flux and permeation of the model compounds. Interestingly, PCA showed that, for the flux of co-applied model permeants through human epidermis, the permeation of the model permeants was better described by a balance between the physicochemical properties of the vehicle and the permeant rather than being dominated solely by the vehicle properties as in the case of synthetic model membranes. The important influence of permeant solubility in the vehicle along with the solvent uptake on overall permeant diffusion into the membrane was substantiated. These results confirm that care must be taken in interpreting permeation data when synthetic membranes are employed as surrogates for human epidermis; they also demonstrate the importance of considering not only the permeant properties but also those of both vehicle and membrane when arriving at any conclusions relating to permeation data.

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“…The protocol for the Franz cell experiments using synthetic membranes are described in detail elsewhere [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Multivariate Analytical Approaches to Identify Key Molecular Properties of Vehicles, Permeants and Membranes That Affect Permeation through Membranes

et al. 2020

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“…Oily vehicles have traditionally been viewed as inert carrier systems for active ingredients and membrane permeation enhancers. Nevertheless, we have demonstrated that oily vehicles also partition extensively into synthetic (silicone, high density polyethylene and polyurethane) membranes [11], despite the conventional belief that such vehicles are inert and non-interacting with barrier membranes. Consequently, the flux of a range of model permeants was shown to be significantly affected by the choice of oily vehicle in which the permeant was applied, despite all formulations being applied having unit thermodynamic activity (i.e., saturated solutions) [11].…”

Section: Introductionmentioning

confidence: 92%

“…Nevertheless, we have demonstrated that oily vehicles also partition extensively into synthetic (silicone, high density polyethylene and polyurethane) membranes [11], despite the conventional belief that such vehicles are inert and non-interacting with barrier membranes. Consequently, the flux of a range of model permeants was shown to be significantly affected by the choice of oily vehicle in which the permeant was applied, despite all formulations being applied having unit thermodynamic activity (i.e., saturated solutions) [11]. As an example of relevance to the current study, the effect of vehicle choice on the transport of methyl paraben (MP), butyl paraben (BP) and caffeine (CF) across silicone membrane are given in Table 1 below.…”

Section: Introductionmentioning

confidence: 92%

“…As an example of relevance to the current study, the effect of vehicle choice on the transport of methyl paraben (MP), butyl paraben (BP) and caffeine (CF) across silicone membrane are given in Table 1 below. The data reported in Table 1 are adapted by recalculation from their original presentation [11] into the more familiar flux (µg cm −2 h −1 ). Table 1.…”

Section: Introductionmentioning

confidence: 99%

“…(HD = hexadecane; IHD = isohexadecane; LP = liquid parafin; OA = oleic acid; IPM = isopropyl myristate; PB = phosphate buffer (pH 7.0)). Previous studies have considered some of the effects of single oils on the diffusion of co-administered permeants [11][12][13]. However, considering the effect of combining two oils within a vehicle, applying that vehicle topically to the membrane and then considering the interaction of those oils with membranes and the possible effects on permeants presented in the formulation has not previously been studied.…”

Section: Introductionmentioning

confidence: 99%

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The Influence of Oily Vehicle Composition and Vehicle-Membrane Interactions on the Diffusion of Model Permeants across Barrier Membranes

et al. 2021

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In many instances, one or more components of a pharmaceutical or cosmetic formulation is an oil. The aims of this study were two-fold. First, to examine the potential of preferential uptake of one oily vehicle component over another into a model barrier membrane (silicone) from blended vehicles (comprising two from the common excipients isohexadecane (IHD), hexadecane (HD), isopropyl myristate (IPM), oleic acid (OA) and liquid paraffin). Second, to study the effect of membrane-vehicle interactions on the diffusion of model permeants (caffeine (CF), methyl paraben (MP) and butyl paraben (BP)) from blended vehicles. Selective sorption and partition of some oils (especially IHD and IPM) at the expense of other oils (such as OA) was demonstrated to take place. For example, the membrane composition of IHD was enriched compared to a donor solution of IHD-OA: 41%, 63% and 82% IHD, compared to donor solution composition of 25%, 50% and 75% IHD, respectively. Pre-soaking the membrane in IHD, HD or LP, rather than phosphate buffer, enhanced the flux of MP through the membrane by 2.6, 1.7 and 1.3 times, respectively. The preferential sorption of individual oil components from mixtures altered the barrier properties of silicone membrane, and enhanced the permeation of CF, MP and BP, which are typically co-formulated in topical products.

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A ‘three in one’ complexing agent enables copper desorption from polluted soil, its removal from groundwater and its detection

Pensini

Laredo

Earnden

et al. 2021

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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Establishing the importance of oil-membrane interactions on the transmembrane diffusion of physicochemically diverse compounds

Cited by 4 publications

References 39 publications

Multivariate Analytical Approaches to Identify Key Molecular Properties of Vehicles, Permeants and Membranes That Affect Permeation through Membranes

Multivariate Analytical Approaches to Identify Key Molecular Properties of Vehicles, Permeants and Membranes That Affect Permeation through Membranes

The Influence of Oily Vehicle Composition and Vehicle-Membrane Interactions on the Diffusion of Model Permeants across Barrier Membranes

A ‘three in one’ complexing agent enables copper desorption from polluted soil, its removal from groundwater and its detection

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