Impact of Alkanediols on Stratum Corneum Lipids and Triamcinolone Acetonide Skin Penetration

Abstract

Alkanediols are widely used as multifunctional ingredients in dermal formulations. In addition to their preservative effect, considering their possible impact on drug penetration is also essential for their use. In the present study, the influence of 2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol on the skin penetration of triamcinolone acetonide from four different semisolid formulations was investigated. Furthermore, confocal Raman spectroscopy measurements were performed to examine the influence of the alkanediols on stratum corneum lipid content and order. Alkanediols were found to increase the penetration of triamcinolone acetonide. However, the extent depends strongly on the formulation used. In certain formulations, 1,2-pentanediol showed the highest effect, while in others the penetration-enhancing effect increased with the alkyl chain length of the alkanediol used. None of the tested alkanediols extracted lipids from the stratum corneum nor reduced its thickness. Notwithstanding the above, the longer-chained alkanediols cause the lipids to be converted to a more disordered state, which favors drug penetration. This behavior could not be detected for the shorter-chained alkanediols. Therefore, their penetration-enhancing effect is supposed to be related to an interaction with the hydrophilic regions of the stratum corneum.

Assessment of penetration and permeation of caffeine by confocal Raman spectroscopy in vivo and ex vivo by tape stripping

“…Recent studies showed that diols, including 1,2-pentanediol, are taken up into SC. It is hypothesized that the hydrophilic regions in the SC might be increased after taking up 1,2-pentanediol and caffeine can thus be deposited in these regions more easily [23]. This can explain the penetration profile of caffeine from the solution containing 1,2-pentanediol obtained by tape stripping, since the lower layer of the stratum corneum, the stratum conjunctum, is more hydrophilic than its upper layer, the stratum disjunctum, as it contains a higher amount of polar lipids [24,25].…”

MALDI-TOF imaging analysis of benzalkonium chloride penetration in ex vivo human skin

“…Thus, vitamin E could be additional protection from the dehydration and degradation that occurs throughout the imaging process. Preservative, caprylyl glycol is a surfactant that can disrupt membranes [ 34 , 47 ]. In our study, treatment with BZK + caprylyl glycol had epidermal thicknesses similar to skin treated with just water.…”

“…Each of these excipients in cosmetic solutions are used as preservatives, emulsion agents, and antioxidants [ 33 ]. Previous studies have shown that caprylyl glycol [ 34 ] and vitamin E [ 35 , 36 ] can influence the penetration of drugs. Two commercial solutions which contain a mixture of several excipients were also analyzed.…”

Novel aspects of Raman spectroscopy in skin research

“…52,54,106,107,108,109 Rodent skin 110 is rarely due to its inherent differences to human skin. Caffeine, 52,106,109,111,112,113 lidocaine, 104 procaine, 107,114 tetracaine, 115 salicylic acid, 113 ibuprofen, 103 flufenamic acid, 105 imiquimod, 116 trans-retinol, 117,118 resorcinol, 75 niacinamide, 119 sulfathiazole sodium, 54 triamcinolone acetonide 120 and oxaprozin are among the most investigated permeants in the CRS penetration studies. 99 Next to these drugs, the penetration of enhancers such as DMSO, 54,121 propylene glycol, 103,106,107,118 polyoxyethylene-23-lauryl ether 107 and other ethoxylated emulsifier systems 114,122 has been evaluated.…”

“…TA B L E 1 Assignment of spectral bands in healthy human skin after 35 The skin penetration of classic anionic surfactants such as sodium dodecyl sulphate (SDS) or sSLES has likewise been investigated in numerous studies, often as positive control. 54,123,124 Regarding skin penetration of additives used in cosmetic or pharmaceutical preparations, data on the penetration behaviour of oils or waxes, 95 preservatives 120 or sunscreen agents 125 have been presented.…”