Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides and amides

Aungst, Bruce J.; Rogers, Nancy J.; Shefter, Eli

doi:10.1016/0378-5173(86)90057-8

Cited by 278 publications

(109 citation statements)

References 22 publications

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“…This is also in contrast with previous findings that suggest a positive or parabolic correlation between hydrophobicity and ER. Among these are the study of Aungst et al [24] indicating a parabolic effect of alkyl chain lengths of enhancers of naloxone penetration through human skin in vitro, and the parabolic relationship observed between the enhancement ratio of ketoprofen percutaneous absorption and octanol/water partition coefficient of cyclohexanol derivatives as the enhancers [25]. However, a number of studies indicate that the enhancing effect of an enhancer depends on actual the permeation pathway of the drug [26,4,27].…”

Section: Discussionmentioning

confidence: 99%

The effect of penetration enhancers on drug delivery through skin: a QSAR study

Ghafourian

Zandasrar

Hamishekar

et al. 2004

Journal of Controlled Release

107

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Skin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin permeable. A full understanding of the mode of action could be beneficial for the design of potent enhancers and for the choice of the enhancer to be used in topical formulation of a special drug. In this study, the structural requirements of penetration enhancers have been investigated using the Quantitative Structure-Activity Relationship (QSAR) technique. Activities of naturally occurring terpenes, pyrrolidinone and Nacetylprolinate derivatives on the skin penetration of 5-fluorouracil, diclofenac sodium, hydrocortisone, estradiol, and benazepril have been considered. The resulting QSARs indicated that for 5-fluorouracil and diclofenac sodium less hydrophobic enhancers were the most active. More precisely, molecular descriptors in the corresponding QSARs indicated the possible involvement of intermolecular electron donor-acceptor interactions. This was in contrast to the skin permeation promotion of hydrocortisone, estradiol, and benazepril by enhancers, where a linear relationship between enhancement activity and n-octanol/water partition coefficients of enhancers was evident. The possible mechanisms of penetration enhancement as suggested by the QSARs will be discussed.3

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Section: Discussionmentioning

confidence: 99%

The effect of penetration enhancers on drug delivery through skin: a QSAR study

Ghafourian

Zandasrar

Hamishekar

et al. 2004

Journal of Controlled Release

107

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“…Naloxone skin permeation study showed that permeation through skin increased as the carbon number in saturated fatty acid increases from 7 to 12 (LA) (Aungst et al, 1986). However, it decreased as the carbon number increased further.…”

Section: Discussionmentioning

confidence: 99%

Effect of Polyoxyethylene Alkyl Esters on Permeation Enhancement and Impedance of Skin

Kim

Oh²

2011

Biomolecules and Therapeutics

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“…shows that the stratum corneum of the human skin is a lipophilic organizational structure and that compounds of high lipophilicity tend to remain in the SC, preventing drugs to transport to the deeper tissues [19]. Evidences from many studies have confirmed that the enhancing effects of fatty acids were most significant for C10 to C12 fatty acids [20,21].In addition, the enhancing effects of fatty acid was also influenced by the bond saturation. Some studies have demonstrated that the unsaturated long-chain fatty acids have been shown a greater enhancer activity when compared to saturated fatty acids of the same chain length.…”

mentioning

confidence: 84%

Review on Transdermal Drug Delivery Systems

Pang¹,

Han²

2014

Journal of Pharmaceutics and Drug Development

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ISSN: 2348-9782 During the past decades, intensive studies have focused on the technologies in drug delivery, and with the rapid developments and explorations in technologies, traditional drug delivery means are being replaced by the more effective and advanced ones. The creation of transdermal drug delivery system (TDDS) has been one of the most sophisticated and innovative approaches of drug deliveries. The transdermal drug delivery system has attracted considerale attention because of its many potential advantages, including better patient compliance, avoidance of gastrointestinal disturbances, hepatic first-pass metabolism and sustained delivery of drugs to provide steady plasma profiles, particularly for drugs with short half-lives, reduction in systemic side effects and enhanced therapeutic efficacy [1][2][3][4][5][6].Recently, transdermal drug delivery system (TDDS) has become a more and more important approach to administering drugs. Based on its advantages, which are not achievable by other modes of administration, many researchers are dedicated to the study of it, and have made great progress. Although the skin offers a painless interface for systemic drug delivery, it also presents limitations which are mainly caused by the stratum corneum. In this work, we state the increasingly impact of TDDS, discuss the limitations of it, and last but not least, we highlight the methods for overcoming these limitations by using permeation enhancers, microneedles, iontophoresis.Despite these advantages, most of the transdermal candidates have low permeability. The drugs administered across skin should have the three constraining characteristics: appropriate partition coefficient, low molecular mass (<500Da), and small required dose (upto milligrams) [3]. The limitations of transdermal drug delivery are caused by skin which protects against and is impermeable to foreign molecules. The human skin is consisted of two main layers: the layer of epidermis and the layer of dermis. Stratum corneum is the epidermis's outermost layer that composed of stratified keratinocytes, multiple lipid bilayers of ceramidas, fatty acids, cholesterol and cholesterol esters. Stratum corneum provides an extremely effective physical barrier for the control of drug penetration [2,[7][8][9][10]. Therefore, attempts to overcome this skin barrier is presently an important area of pharmaceutical and toxicological research. The techniques that weaken the barrier have included permeation enhancers , microneedles and iontophoresis [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84]. Chemical permeation enhancersIn the last 50 years, a large number of chemical permeation enhancers (CPEs) which are defined as substances that interact with the major constituents of skin barrier, stratum corneum, to promote penetration of drugs into skin.The ideal enhancer should have the following conditions: 1. Non-pharmacological activities. 2. Nontoxic,. Rapid-acting with predictable and reproducible activity. 4. When removed from the skin...

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Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides and amides

Cited by 278 publications

References 22 publications

The effect of penetration enhancers on drug delivery through skin: a QSAR study

The effect of penetration enhancers on drug delivery through skin: a QSAR study

Effect of Polyoxyethylene Alkyl Esters on Permeation Enhancement and Impedance of Skin

Review on Transdermal Drug Delivery Systems

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