In vitro evaluation of a series of Azone analogs as dermal penetration enhancers: IV. Amines

Michniak, B. B.; Player, Mark R.; Godwin, Donald A.; Phillips, Christine A.; Sowell, J. Walter

doi:10.1016/0378-5173(94)00294-f

Cited by 26 publications

(34 citation statements)

References 21 publications

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“…The alkyl chain lengths for which ER Q24 was greatest were observed to be different for the 2-oxopyrrolidine-R-acetic acid ester group (1-7) and the 2-oxopiperidine-R-acetic acid ester group (8)(9)(10)(11)(12)(13)(14). Q 24 maxima were reached with acetic acid decyl and tetradecyl ester moieties for 2-piperidinone (10 and 14); in contrast, the 2-pyrrolidinone nucleus exhibited Q 24 maxima with acetic acid decyl and dodecyl ester substitutents (3 and 5).…”

Section: Resultsmentioning

confidence: 96%

“…29,30 Dorsal mouse skin samples were placed in diffusion cells and were allowed to equilibrate for 1.5 h. At this time the enhancer solution (0.4 M) in 5 µL propylene glycol was spread on the diffusional area. Although solid enhancers are normally applied at their saturation solubilities if they are under 0.4 M, all of the solid enhancers in the present work (12)(13)(14) were soluble at 0.4 M and 32 ( 0.5°C. One hour after enhancer pretreatment, hydrocortisone 21-acetate (0.03 M) suspended in 500 µL of propylene glycol was spread on the skins.…”

Section: Methodsmentioning

confidence: 99%

“…Synthesis of Lactam N-Acetic Acid EsterssThe 5-and 6-membered lactams (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were prepared with acetate esters at the 1-position (Table 1). The bromoacetate esters were prepared by reaction of the appropriate alcohol with bromoacetyl bromide, and this crude bromoacetate ester was used to alkylate the sodium salt of the various lactams.…”

Section: Methodsmentioning

confidence: 99%

“…Azone has been the most widely studied chemical penetration enhancer of the 1980s although a considerable number of analogues with improved activity have been described. [12][13][14][15][16][17][18] Several studies suggest that Azone acts by solubilizing or increasing the entropy of highly ordered stratum corneum lipids. 19 Skin conductance experiments suggest that Azone also increases skin water content.…”

mentioning

confidence: 99%

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Synthesis and in Vitro Transdermal Penetration Enhancing Activity of Lactam N-Acetic Acid Esters

Michniak¹,

Player²,

Sowell³

1996

Journal of Pharmaceutical Sciences

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A homologous series of N-acetic acid esters of 2-pyrrolidinone and 2-piperidinone has been prepared and evaluated for its ability to enhance the skin content and flux of hydrocortisone 21-acetate in hairless mouse skin in vitro. Enhancement ratios (ER) were determined for flux (J), 24-hour diffusion cell receptor cell concentrations (Q24), and 24-h full-thickness mouse skin steroid content (SC) and compared to control values (no enhancer present). In addition, in an attempt to abrogate toxicity, these dermal penetration enhancers were designed to have the potential for biodegradation by dermal esterases. 2-Oxopyrrolidine-alpha acetic acid dodecyl ester (5) showed the highest enhancement ratios for J (ER 67.33) and Q24 (ER 180.66). 2-Oxopiperidine-alpha-acetic acid decyl ester (10) showed a high Q24 (ER 162.07) but a lower J (ER 12.67). 2-Oxopyrrolidine-alpha-acetic acid decyl ester (3) showed the highest enhancement ratio for SC (ER 8.7). The ER Q24 for 3, 5 and 10, as well as other lactam N-acetic acid esters in this work, were significantly higher than the ER found using Azone as enhancer.

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Section: Resultsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Synthesis and in Vitro Transdermal Penetration Enhancing Activity of Lactam N-Acetic Acid Esters

Michniak¹,

Player²,

Sowell³

1996

Journal of Pharmaceutical Sciences

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“…Several authors have reported on the structure-activity relationships in series of chemical modifiers (13)(14)(15)(16)(17). Moreover, based on the mechanisms of the action of penetration modifier, a number of related factors affecting on the course of enhancement/retardation have been reported, e.g., the chain length effect (18).…”

Section: Introductionmentioning

confidence: 99%

Effect of Hydrocarbon Chain Length in 1,2-Alkanediols on Percutaneous Absorption of Metronidazole: Toward Development of a General Vehicle for Controlled Release

Jia

Zhang

et al. 2014

AAPS PharmSciTech

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Abstract. The objective of the present study is to investigate the effect of hydrocarbon chain length in 1,2-alkanediols on percutaneous absorption of metronidazole (MTZ). Twelve formulations (1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol in 4% concentration, 1,2-hexanediol, and 1,2-heptanediol in 1% concentration, in the absence and presence of 1,4-cyclohexanediol, respectively) were studied in an in vitro hairless mouse skin model using Franz diffusion cell. Based on the flux values and retardation ratios (RR), a penetration retardation effect on percutaneous absorption of MTZ was observed for the formulations containing 1,2-diols having six-to seven-carbon chain in the presence of 1,4-cyclohexanediol (1,2-hexanediol with chain length of six hydrocarbons, RRs are 0.69 and 0.76 in the concentration of 4% and 1%, respectively; 1,2-heptanediol with chain length of seven hydrocarbons, RR is 0.78 in the concentration of 1%). On the other hand, no retardation effect was observed in formulations containing short alkyl chains (RRs of 1,2-propanediol, 1,2-butanediol, and 1,2-pentanediol are 0.99, 1.61, and 0.96, respectively). Instead, a penetration enhancement effect was observed for 1,2-diols having four and five carbons. In other words, effect of 1,2-alkanediols on percutaneous absorption of MTZ can be systematically modulated by simply varying number of -CH 2 groups in the hydrocarbon chain-from being a penetration enhancer to retardant. These observations shed light on mechanism of the penetration enhancement and retardation effect and provide insight into rational design of penetration enhancers and retardants. Furthermore, the combination of 1,2-alkanediols and 1,4-cyclohexanediol could become a general vehicle for controlled release of pharmaceutical and cosmetic active ingredients.

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QSAR Analyses of Skin Penetration Enhancers.

et al. 2007

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In vitro evaluation of a series of Azone analogs as dermal penetration enhancers: IV. Amines

Cited by 26 publications

References 21 publications

Synthesis and in Vitro Transdermal Penetration Enhancing Activity of Lactam N-Acetic Acid Esters

Synthesis and in Vitro Transdermal Penetration Enhancing Activity of Lactam N-Acetic Acid Esters

Effect of Hydrocarbon Chain Length in 1,2-Alkanediols on Percutaneous Absorption of Metronidazole: Toward Development of a General Vehicle for Controlled Release

QSAR Analyses of Skin Penetration Enhancers.

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