Influence of membrane-solvent-solute interactions on solute permeation in model membranes.
ABSTRACT The interaction of the components of topical formulations with the skin is an important consideration for effective drug delivery and efficacy. The relative importance of solubility parameters and other solvent properties on membrane diffusion processes has not been fully elucidated in the literature. In this paper, the effect of different vehicles on the permeation of caffeine, salicylic acid and benzoic acid through silicone membranes was evaluated. Polydimethylsiloxane membranes were used as model membranes for comparing the release characteristics of saturated solutions of model permeants because of their homogeneity and uniformity. Log P (octanol-water partition coefficient) and solubility parameter values were calculated for the compounds under study. In vitro diffusion studies indicated that the permeation profiles of all solutes showed a similar pattern. The permeation rates of benzoic acid and salicylic acid through silicone membrane from saturated solutions were higher than those for caffeine reflecting the more lipophilic nature of these compounds in comparison with caffeine. Solvent uptake studies confirmed that the vehicles that were highly sorbed by the membrane altered its properties and hence the flux. Vehicles that were not sorbed by the membrane showed similar steady-state fluxes for the model drugs. This suggests that the diffusion process is mainly influenced by the interactions between the vehicles and the membrane. Solubility parameter alone cannot explain the interactions between the membrane and the vehicles in all cases. Rather, it is likely that membrane flux reflects a combination of different solvent and solute characteristics, such as size, shape and charge distribution.
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ABSTRACT: We investigate theoretically and experimentally how the rate and extent of membrane permeation is affected by switching the donor delivery solvent from water to squalane for different permeants and membranes. In a model based on rate-limiting membrane diffusion, we derive explicit equations showing how the permeation extent and rate depend mainly on the membrane-donor and membrane-receiver partition coefficients of the permeant. Permeation results for systems containing all combinations of hydrophilic or hydrophobic donor solvents (aqueous solution or squalane), permeants (caffeine or testosterone) and polymer membranes (cellulose or polydimethylsiloxane) have been measured using a cell with stirred donor and re-circulating receiver compartments and continuous monitoring of the permeant concentration in the receiver phase. Relevant partition coefficients are also determined. Quantitative comparison of model and experimental results for the widely-differing permeation systems successfully enables the systematic elucidation of all possible donor solvent effects in membrane permeation. For the experimental conditions used here, most of the permeation systems are in agreement with the model, demonstrating that the model assumptions are valid. In these cases, the dominant donor solvent effects arise from changes in the relative affinities of the permeant for the donor and receiver solvents and the membrane and are quantitatively predicted using the separately measured partition coefficients. We also show how additional donor solvent effects can arise when switching the donor solvent causes one or more of the model assumptions to be invalid. These effects include a change in rate-limiting step, permeant solution non-ideality and others.Physical Chemistry Chemical Physics 10/2012; 14(44):15525-38. · 3.83 Impact Factor
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ABSTRACT: Previous work from this group has focused on the molecular mechanism of alcohol interaction with model membranes, by conducting thermodynamic and kinetic analyses of alcohol uptake, membrane partitioning and transport studies of a model compound (i.e. methyl paraben) in silicone membranes. In this article, similar membrane transport and partitioning studies were conducted in silicone membranes to further extend the proposed model of alcohol interactions with silicone membranes to include other vehicles more commonly used in dermal formulations, that is, isopropyl myristate (IPM), dimethyl isosorbide (DMI), polyethylene glycol (PEG) 200, PEG 400 and Transcutol P(®) (TC). More importantly, membrane partitioning studies were conducted using human SC to evaluate the application of the proposed model of solvent-enhanced permeation in simple model membranes for the more complex biological tissue. The findings support a model of vehicle interactions with model membranes and skin where high solvent uptake promotes drug partitioning (i.e. K) by enabling the solute to exist within the solvent fraction/solvent-rich areas inside the membrane or skin in a concentration equivalent to that in the bulk solvent/vehicle. High solvent sorption may also ultimately impact on the membrane diffusional characteristics, and thus the diffusion coefficient of the solute across the membrane. The implications for skin transport are that increased partitioning of a drug into the SC may be achieved by (i) selecting vehicles that are highly taken up by the skin and also (ii) by having a relatively high concentration (i.e. molar fraction) of the drug in the vehicle. It follows that, in cases where significant co-transport of the solvent into and across the skin may occur, its depletion from the formulation and ultimately from the skin may lead to drug crystallization, thus affecting dermal absorption.International journal of cosmetic science 08/2012;
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ABSTRACT: The purpose of this work was to investigate the effect of solute-membrane interaction under supersaturated conditions on the transport of model solute (salicylic acid) across poly(dimethylsiloxane) (PDMS) membrane. Supersaturated systems with a degree of saturation (DS) up to 8 were prepared using a molecular form technique with water as the vehicle to minimize the vehicle-membrane interaction. The spectroscopic and thermal analysis revealed the presence of both hydrogen bonding and nonpolar interaction between the solute and PDMS. Upon treatment by supersaturated solutions the degree of solute-membrane interaction increased with increasing DS. This enhanced the barrier property of PDMS and thus led to the flux attenuation compared to that calculated by Higuchi equation. This work highlighted the importance of solute-membrane interaction under supersaturation in the flux reduction, which should be considered when designing, and optimising supersaturated topical and transdermal drug delivery systems.International journal of pharmaceutics 11/2012; · 2.96 Impact Factor