Penetration enhancer azone

Wiechers, J.W. 1989. Absorption, distribution, metabolism, and excretion of the cutaneous penetration enhancer azone. PhD thesis, University of Groningen. 

Wiechers, J.W., and R.A. de Zeeuw. 1990. Transdermal drug delivery Efficacy and potential applications of the penetration enhancer azone. Drug Design Del 6 87. 

J. Engblom, S. Engstrom, and K. Fontell, The effect of the skin penetration enhancer Azone on fatty acid-sodium soap-water mixtures, J. Control. Rel. 33 299— 305 (1995). 

Goodman, M. and Barry, B. W. Differential scanning calorimetry of human stratum comeum effects of penetration enhancers azone and dimethyl sulphox-ide. Analytical Proceedings 23 397-398, 1986. 

Engblom, J. The bicontinuous cubic phase—A model for investigating the effects on a lipid bilayer due to a foreign substance illustrated by the skin penetration enhancer Azone. Chemistry and Physics of Lipids S4(2) 155-164, 1996. 

Baker, E. J., and J. Hadgraft. 1995. In vitro percutaneous absorption of arildone, a highly lipophilic drug, and the apparent no-effect of the penetration enhancer Azone in excised human skin. Pharm. Res. 

Bezema, FR., Marttin, E, Roemele, RE.H., Brussee, J., Bodde H.E., and de Groot, H.J.M. (1996). NMR evidence for dynamic disorder in human skin induced by the penetration enhancer Azone, Spectrochim. Acta Part A Mol. Spectrosc., 52 785-791. 

Wiechers, J.W., Drenth, B.E, Adolfsen, EA., Prins, L.,anddeZeeuw,RA. (1990). Disposition and metabolic profiling of the penetration enhancer Azone. I. In vivo studies urinary profiles of hamster, rat, monkey, and man, Pharm. Res., 7 496-499. 

Transdermal delivery of certain APIs is now common for the treatment of some medical conditions, and there are several excipients that are promoted as transdermal penetration enhancers. One of the earlier materials developed was laurocapram (Azone ). There is a detrimental interaction between laurocapram and mineral oil (liquid paraffin) whereby when both are included in the same formulation, the skin penetration-enhancing properties of laurocapram are lost. Such interactions have implications for extemporaneous mixing of different cream and ointment formulations in the pharmacy. 

Penetration enhancers have different mechanisms of action depending on their physicochemical properties. Some examples of penetration enhancers and their mechanisms are bile salts (micellization and solubilization of epithelial lipids), fatty acids such as oleic acid (perturbation of intracellular lipids) [25,26], azone (l-dodecylazacycloheptan-2-one) (increasing fluidity of intercellular lipids), and surfactants such as sodium lauryl sulfate (expansion of intracellular spaces). The complete list of enhancers and their mechanism of actions are discussed in detail in Chapter 10. 

Nicolazzo et al. [52] considered the use of the lipophilic skin penetration enhancers, octisalate and padimate (both used in sunscreens), in comparison to Azone on the buccal absorption of various drugs in vitro. They were found to have limited effect in enhancing the permeation of triamcinolone acetonide (although some increase in tissue uptake was proposed in some cases) relative to Azone, while reducing the penetration of estradiol and caffeine. One interesting report is that of the effect of capsaicin from capsicum, a commonly used food ingredient, which has been reported to enhance the permeability of sulfathiazole in human volunteers [53] presumably by a direct irritation effect on the mucosa. This raised an interesting issue of the effect of diet on oral mucosal permeability. 

Hadgraft, J., D.G. Williams, and G. Allan. 1993. Azone mechanism of action and clinical effect. In Pharmaceutical Skin Penetration Enhancement, ed. Walters, K.A., and J. Hadgraft, 175. New York Marcel Dekker. 

FIGURE 12.3 Azone, the original molecule synthesized specifically to act as a skin penetration enhancer. 

Ismail, I.M., et al. 1992. Comparison of azone and hexamethylene lauramide in toxicologic effects and penetration enhancement of cimetidine in rabbit eyes. Pharm Res 9 817. 

The most extensively studied amphiphilic and lipophilic penetration enhancers are oleic acid, oleyl surfactants, terpenes, alcohols, azone, azone analogues [84— 86], and FFAs. 

Michniak, B.B., et al. 1993. In-vitro evaluation of a series of azone analogs as dermal penetration enhancers. Int.]. Pharmaceutics 91 85-93. 

Lee, G. Interaction of Azone with model lipid systems. In Percutaneous Penetration Enhancers. E. W. Smith and H. I. Maibach, eds. CRC Press Boca Raton, 1995, pp. 277-287. 

Penetration enhancers such as azone and dodecyl N, A-dimethylamino-acetate appear to increase the skin s impedance [13]. The authors speculate that this may be related to the fact that these enhancers increase the skin s heterogeneity (as assessed, in part, by an observed increase in the skin s... 

Beastall, J., Hadgraft, J. and Washington, C. (1988). Mechanism of action of Azone as a percutaneous penetration enhancer Lipid bilayer fluidity and transition temperature effects. Int. J. Pharm. 45 207-213. 

Hirvonen et al. [67] used dodecyl NA -dimethyl amino acetate (DDAA) and Azone as penetration enhancers in the transdermal iontophoresis of sotalol and salicylate. They compared the action of both enhancers in passive diffusion studies and iontophoretic studies and found no significant difference between the two, with the permeability of sotalol in the passive diffusion studies increasing to the order of magnitude found in the iontophoretic studies. The main mechanism of action of DDAA and Azone is the disordering of the lipids and the closing of iontophoretic penetration routes [123,124]. 

Hadgraft, J. Peck, J. Williams, D.G. Pugh, W.J. Allan, G. Mechanisms of action of skin penetration enhancer retarders azone and analogues. Int. J. Pharm. 1996, 141, 17-25. 

Bouwstra, J.A. Bodde, H.E. Human stratum corneum barrier impairment by iV-alkylazacycloheptanones a mechanistic study of drug flux enhancement, Azone mobility and protein and lipid perturbation. In Percutaneous Penetration Enhancers Smith, E.W., Maibach, H.I., Eds. CRC Press Boca Raton, Florida, 1995 137-169. 

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