Transdermal penetrants Azones

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. 

Azone (l-Dodecylazacycloheptan-2-one) and related compounds have been studied as transdermal penetration and oral absorption enhancers. Although some efficacy has been shown, an emulsifying agent appears to be necessary for azone to penetrate the intestinal mucosal membrane in order to promote drug absorption. One study reported the absence of gross morphological damage after exposure of mucosa to azone but additional information on the effect of azone on overall mucosa structure is not avalable. 

Liquid crystalline phases also seem to play an important role in topical and transdermal drug delivery. As discussed above, the protective properties of the stratum corneum seems to depend on the properties of its lipid fraction. More specifically, these have been found to form lamellar structures (169, 170), which could be expected to reduce the transdermal penetration of drugs, as well as water evaporation. On the other hand, the presence of Azone may induce reversed-type phases (172). Thus, the generation of oil and water channels seems to correlate with the commonly observed enhanced transdermal penetration of drugs caused by this penetration enhancer (186). 

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. 

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]. 

Phillips, C.A. Michniak, B.B. Transdermal delivery of drugs with differing lipophilicities using azone analogs as dermal penetration enhancers. J.Pharm.ScL, 1995, 84, 1427-1433... 

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