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

Abstract

Objective: Tape stripping is an often-used non-invasive destructive method to investigate the skin penetration of a substance. In recent years, however, the suitability of confocal Raman spectroscopy (CRS) as a non-invasive method of nondestructive examination of the skin has become increasingly apparent. In this study, we compared invasion and depletion penetration and permeation kinetics of a 2% caffeine solution with and without 1,2-pentanediol as a penetration enhancer measured with CRS and tape stripping.Methods: Porcine skin was used for tape stripping and human skin for CRS. 2% caffeine solution was applied to the skin for different incubation times. Human skin was then examined by CRS while caffeine was extracted from porcine skin and quantified via reverse-phase HPLC. Fluxes were also measured and calculated by sum of the total amounts of caffeine penetrated into the skin.Results: Without penetration enhancers, there is hardly any difference between the penetration profiles of the two measurement methods for invasion, but the curves for depletion are different. Furthermore, the calculated flux values for the invasion are almost identical, but for the depletion the tape stripping values are about twice as high as the CRS values. Conclusion:The relevance of conducting invasion and depletion studies became clear and was able to show the still existing problems in the comparability of CRS and tape stripping.

Progress in Topical and Transdermal Drug Delivery Research—Focus on Nanoformulations

“…Although regulatory bodies have not yet adopted the method in their guidelines, research is generating more and more evidence to correlate CRS data to date from conventional methods like tape stripping. For example, Kourbaj et al [ 161 ] and Krombholz et al [ 162 ] showed that the penetration of caffeine and retinol can be monitored by CRS as well as by tape stripping and provide similar results. They described two important advantages of CRS.…”

Quantification of skin penetration of caffeine and propylene glycol applied topically in a mixture by tailored multivariate curve resolution‐alternating least squares of depth‐resolved Raman spectra

“…This discrepancy might be explained by the higher capability of PCA-LDA to detect CF and PG in the SC. Moreover, it is established that the PG, as a penetration enhancer, can reach the SC bottom and even permeate the SC, while CF 29,30,39]. In addition, it should be taken into consideration that the barrier function of SC in porcine skin ex vivo is lower than in human skin in vivo [86], so we expect that under real in vivo conditions in humans, the penetration depth of CF and PG will be lower.…”

“…The SC's barrier is more resistant to hydrophilic than to lipophilic substances [28], so transdermal delivery of hydrophilic drugs remains a real challenge. Therefore, a large amount of topically applied hydrophilic CF resides on the skin surface [2] and saturates mainly the outermost SC [29,30]. To solve the problem of permeation through the skin barrier, invasive methods such as microneedling, electroporation, iontophoresis, ultrasound, intradermal injection (including jet injection), and their combination are used to deliver CF into the dermis [31,32].…”

“…Noninvasive methods used for the quantitative/ qualitative determination of the penetration of CF and PG into the skin are limited to optical methods such as confocal Raman micro-spectroscopy (CRM) [29,30,[42][43][44][45], stimulated Raman scattering microscopy [46], twophoton tomography combined with fluorescence lifetime imaging [21,47], and laser scanning microscopy (labeling of the drug with a fluorescent dye is required) [48]. Invasive methods include the high-performance liquid chromatography analysis of SC tape strips [21,30] and of the skin interstitial fluid collected with microneedles [17]. For in vitro and ex vivo studies on skin models or skin biopsies, the "Franz Diffusion Cell" [49,50], Skin-parallel artificial membrane permeability assay (PAMPA) [21] and "Multi In vitro Organ" [51] methods can be used in addition to conventional histology.…”

Optical Methods for Non-Invasive Determination of Skin Penetration: Current Trends, Advances, Possibilities, Prospects, and Translation into In Vivo Human Studies

“…Tape-stripping-based lowinvasive ATR-FTIR and EPR spectroscopy methods are commonly used in in vivo skin penetration studies, but require special permission and are severely limited in patients. Low-invasive methods can be applied both in vivo and ex vivo and include tape stripping, primarily applied at the SC [16][17][18]; cyanoacrylate stripping applicable to the SC and viable epidermis [18,19]; suction blister after the application of partial negative pressure on the skin with further analysis of the accumulated interstitial and serum fluids [20]; sampling of the interstitial fluid from the viable epidermis and/or dermis with microneedles [21][22][23] or by microdialysis [24,25], followed by an analysis with validated methods (or their combinations) such as autoradiography for the detection of the radioisotopelabelled penetrants [26], high-performance liquid chromatography, mass spectrometry of various modifications, or UV/VIS spectroscopy (absorption or (epi)fluorescence in a specific spectral range) [26][27][28][29][30]. The skin penetration profile can be determined using low-invasive attenuated total reflectance Fourier-transform infrared (ATR-FTIR) [31][32][33], Fourier-transform infrared photoacoustic spectroscopy (FTIR-PAS) [31], thermal emission decay-Fourier-transform infrared (TED-FTIR) spectroscopy [34], and electron paramagnetic resonance (EPR) spectroscopy [35] for the analysis of the SC removed from skin with tape or cyanoacrylate stripping.…”