Azone analogues: classification, design, and transdermal penetration principles

Abstract

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).

Rapid Screening of Mupirocin Skin Permeation Modification by Micronized and Nanonized Alaptide

“…Based on the above mentioned facts and structural analogy with other CPEs, it was suggested to evaluate alaptide as a potential CPE of many anti-inflammatory drugs, antimicrobial chemotherapeutics, sex hormones/genital system modulators, or drugs targeting the central/vegetative nervous system [4,32,33]. Furthermore, the permeation of micronized (ALA) and nanonized (NALA) alaptide alone through the full-thickness pig ear skin from various semi-solid compositions was evaluated and different behaviour among both forms was confirmed.…”

Investigation of permeation of acyclovir through skin using alaptide

“…Skin samples were slowly thawed (at 4°C overnight and then at ambient temperature) before each experiment [12,13]. The penetration enhancing effect of alaptide was evaluated in vitro, using a vertical Franz diffusion cell (SES -Analytical Systems, Bechenheim, Germany) with a donor surface area of 0.6359 cm 2 and a receptor volume of 5.2 mL (see Figure 2). The skin was mounted between the donor and receptor compartments of the Franz diffusion cell with the epidermal side up.…”

“…The use of chemical permeation enhancers (CPEs) is one of the approaches for facilitating drug delivery through the skin -modification of SC [1]. Small polar molecules containing a characteristic fragment of heteroatoms X−CO−N=, where X is −CH 2 −, −NH 2 , or −NH−, may break intermolecular H-bonds that hold ceramides together in the SC [2].…”

Rapid Screening of Permeation of Rutin through Skin Using Alaptide Enantiomers

“…1) was designed as an analogue of melanocyte-stimulating hormone release-inhibiting factor (MIF-1) [7−10] and thus is able to influence the creation and function of keratinocytes [11−13]. Based on these facts and structural analogy with other CPEs [4], it was suggested to investigate alaptide as a potential CPE of many anti-inflammatory drugs, antimicrobial chemotherapeutics, sex hormones/genital system modulators or drugs of central/vegetative nervous system [14−16]. Permeation through the skin of micronized and nanonized (S)-alaptide from semisolid formulations was investigated recently [17], and the transdermal modifying effect of micronized and nanonized (S)-alaptide was also described [14][15][16]18,19].…”

“…Today more than 4000 flavonoid-based compounds were described [24,25]. Flavonoids are glycosides containing aglycone derived from benzopyran (chromene) with lateral phenyl in the positions C (2) , C (3) or C (4) of the benzopyran scaffold. The phenyl rings are marked A and B, and the pyran ring C is ortho-condensed with the ring A.…”