Non-ionic emulsifiers are commonly found in existing pharmaceutical and cosmetic formulations and have been widely employed to enhance the penetration and permeation of active ingredients into the skin. With the potential of disrupting skin barrier function and increasing fluidity of stratum corneum (SC) lipids, we herein examined the effects of two kinds of non-ionic emulsifiers on intercellular lipids of skin, using confocal Raman spectroscopy (CRS) with lipid signals on skin CRS spectrum. Non-ionic emulsifiers of polyethylene glycol alkyl ethers and sorbitan fatty acid esters were studied to obtain a deep understanding of the mechanism between non-ionic emulsifiers and SC lipids. Emulsifier solutions and dispersions were prepared and applied onto excised porcine skin. Water and sodium laureth sulfate solution (SLS) served as controls. SC lipid signals were analysed by CRS regarding lipid content, conformation and lateral packing order. Polyethylene glycol (PEG) sorbitan esters revealed no alteration of intercellular lipid properties while PEG-20 ethers appeared to have the most significant effects on reducing lipid content and interrupting lipid organization. In general, the polyoxyethylene chain and alkyl chain of PEG derivative emulsifiers might indicate their ability of interaction with SC components. HLB values remained critical for complete explanation of emulsifier effects on skin lipids. With this study, it is possible to characterize the molecular effects of non-ionic emulsifiers on skin lipids and further deepen the understanding of enhancing substance penetration with reduced skin barrier properties and increased lipid fluidity.

Ex-vivo and in-vivo skin analysis has been extensively evaluated by confocal Raman spectroscopy (CRS). The off-line measurement with a CRS-suited skin-mounted device after Franz-cell incubations is the most popular choice. However, real-time monitoring of in-line measurement has clear advantages for obtaining dynamic and more timely results. In our study, a custom-built setup suitable for in-line measurements was implemented, which ensures constant skin incubation and in-situ skin detections. We aim to compare the differences between using in-line and off-line devices for monitoring skin drug penetrations. A well-assessed formulation gel with procaine-HCl as the active ingredient was used as reference. The PEG-23 lauryl ether was added to the formulation as a penetration enhancer to evaluate the enhancement effects of procaine on skin. After incubation times of 14, 20, and 24 h, skin penetration profiles were assessed. Comparable results between off-line and in-line measurements were obtained. Remarkable improvements in penetrated procaine amount and depth were observed. Based on the significant differences of their enhanced penetration amounts, fairly similar estimations were achieved from both methods. A slight difference of 14 h incubation between these two setups can still be found, which may be due to the different detection conditions and affected skin properties. Overall, in-line measurements could provide a more time- and labor-saving alternative for off-line measurements in ex-vivo study.