Azone analogues: classification, design, and transdermal penetration principles

The development in the field of pharmaceutical dosage forms results in the discovery of additional highly sophisticated drug delivery systems that allow maintaining a constant level of the active substance in an organism. Transdermal therapeutic systems are an excellent alternative to conventional pharmaceutical dosage forms. However, the application of transdermal drug delivery faces the problem of insufficient or no penetration of active pharmaceutical substances through the skin. This review article describes the possible fundamental mechanisms of penetration through the skin barrier and refers to the classification of skin penetration enhancers. Azone-like enhancers are considered in detail and classified according to their structure on the basis of medicinal chemistry approaches. The article also provides a review of original transdermal penetration enhancers prepared in our laboratory and discusses the relationship between the chemical structure of the described Azone analogues and their penetration activity (SAR/QSAR).