Percutaneous Absorption of Alkanoic Acids 11: Application of Regular Solution Theory

Liron, Zvi; Cohen, Sasson

doi:10.1002/jps.2600730426

Cited by 81 publications

(32 citation statements)

References 9 publications

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“…Given that the larger compounds are also the more lipophilic, it is not clear whether the decrease in J max for the more lipophilic solutes arises from the increase in molecular weight, or other phenomena. Alternatives include: an altered diffusion pathway for penetration in the stratum corneum (1,5,19,23); a reduced flux due to a change from a rate-limiting diffusion process through the stratum corneum to a rate-limiting partitioning across the stratum corneum-viable epidermis interface (if solubility levels in viable epidermis are approached) (32); a dependence on the mole fraction solubility in the stratum corneum (35,36); a contribution to barrier resistance by the viable epidermis (13), dermis (5) or aqueous diffusion layers (6), and a decreased clearance from the dermis or receptor phase (37). Enhanced penetration can also be achieved by supersaturating the vehicle, leading to an enhanced partitioning into the stratum corneum, as a consequence of the antinucleating ability of the intercellular lipids of the stratum corneum (38).…”

Section: Introductionmentioning

confidence: 99%

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Zhang

Grice

et al. 2009

Pharm Res

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A key finding is that the convex dependence of maximum flux on lipophilicity arises primarily from variations in stratum corneum solubility, and not from diffusional or partitioning barrier effects at the stratum corneum-viable epidermis interface for the more lipophilic phenols. Our data support a solute structure-skin transport model for aqueous solutions in which permeation rates depend on both partitioning and diffusivity: partitioning is related to P, and diffusivity to solute size and hydrogen bonding.

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Section: Introductionmentioning

confidence: 99%

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Zhang

Grice

et al. 2009

Pharm Res

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“…There has been the proposition that this can be estimated using the solubility parameters of the permeant, the solvent and skin. The latter is often ascribed a value of between 9 and 10 (cal/cm 3 ) 0.5 [11]. If the permeant has a solubility parameter (‰) greater than 10, e.g.…”

Section: Penetration Enhancers That Influence Kmentioning

confidence: 99%

Modulation of the Barrier Function of the Skin

Hadgraft

2001

Skin Pharmacol Physiol

109

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Transport of xenobiotics across the stratum corneum, the rate-controlling membrane of skin, is slow and the mechanism appears complex. However, the basic transfer is controlled by fundamental physicochemical concepts, the predominant of which are partition (K), diffusion (D) and solubility (C_s). In order to change the rate of penetration it is therefore clear that it is these parameters that should be targeted. In most instances enhancement strategies are adopted to improve D, K or C_s, however there are instances in which permeation reduction may be beneficial. Examples include the topical application of sunscreens or insect repellents. This publication demonstrates the way in which modulation effects can be assessed and the difficulties involved in determining which of the physicochemical parameter(s) are being affected. If the formulation influences more than one, synergism can often be seen. Advances in computer modelling have provided an insight into the mechanisms of action of some of the chemical enhancers at a molecular level. Enhanced skin absorption has been reported for the delivery of macromolecules such as insulin (associated with transfersomes) or DNA (as a DOTAP complex). The barrier property of the skin must be modulated for this to be achieved. However the precise mechanisms of action have not been elucidated.

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“…An ideal enhancer should have solubility parameter similar to that of the skin (53). It can be seen from (54). Therefore, it might be hypothesized that such enhancers should mix freely with the stratum corneum lipids and have maximal enhancement properties.…”

Section: Penetration Enhancement Of Lactate Esters On Percutaneous Pementioning

confidence: 99%

In vitro Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

et al. 2010

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Abstract. Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a constant driving force with maximum thermodynamic activity. The permeability coefficient (K p ), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10-12 are more effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity, which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%. In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety of penetration enhancers is a prime consideration.

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Percutaneous Absorption of Alkanoic Acids 11: Application of Regular Solution Theory

Cited by 81 publications

References 9 publications

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Modulation of the Barrier Function of the Skin

In vitro Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

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