Using Confocal Raman Analysis on Transdermal Patches

Transdermal patches offer an easy, non-invasive way to deliver medication to patients. By adhering to skin and systematically releasing pharmaceutical drugs into the bloodstream, they have been used for both targeted and generalized medication delivery.

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The Nicotine transdermal patch for example, has been used for nicotine replacement therapy; helping patients to stop smoking. Structurally, most patches are made up of multiple layers – the release liner (which protects the adhesive and membrane layers and is removed before application), the adhesive, the membrane (where the drug is contained and which controls the diffusion rate) and the backing (the outermost layer).

To continue developing and improving these kinds of medication delivery systems, it is vital to analyze and observe both their method of drug release and the composition of their layers.

However, it is very difficult to do so without damaging the product – they often need to be cross-sectioned or dissolved for any further examination to take place. These methods can also be incredibly lengthy and labor intensive.

Image credit: Daniel Houghton/shutterstock

Image Credit: Daniel Houghton/

Using a Thermo Scientific™ DXR™2 Raman microscope (532 nm laser, 5mW laser power, 50X objective, 25μm confocal pinhole aperture, auto exposure), researchers attempted to carry out non-invasive analysis on a commercially available transdermal nicotine patch.

Mounted onto a gold-coated slide (the backing layer facing the lens), confocal Raman analysis was performed; including Raman confocal line depth profiling (also known as Z-profiling) and area depth profiling. For data collection and processing, including layer thickness estimation, the Thermo Scientific™ OMNIC™ for Dispersive Raman Software Suite was used.

To correlate the Raman profile with an optical image, researchers vertically mounted a cross sectional piece of the nicotine patch on a glass slide.

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Without damaging the transdermal sample, researchers were able to determine the chemical composition of each layer of the patch. Using OMNIC for Dispersive Raman and OMNIC Specta Software suites, they carried out multi-component spectral analysis on each of the transdermal layers.

Layer three was also analyzed with the OMNIC Specta Multi-Component Library Search, which replaced the required manipulations for traditional search and subtract processing and also provided the percentage of the components.

A profile map of the Raman line depth results was produced, displaying in a 2-D contour map. Changes in the vertical lines (also known as Raman peaks) were revealed as the focal point probes through the layers and the colors showed the intensity of the Raman peaks.

Six layers were formally identified and ranged in thickness from ~15 μm to ~75 μm. Layer 1 and 6 were made up of poly(ethylene terephthalate)/PET. Layers 2 and 4 were composed of microporous polyethylene/PE, a nicotine release agent.

Layer 3 was considered the ethylene/vinyl acetate copolymer (EVA) reservoir and is also where the nicotine was located. Layer 5 was made up of a polyisobutylene (PIB) adhesive and PET.

The whole analytical process was significantly quicker than the previous destructive methods and the sample was much easier to prepare. Ideally, in future research on multilayer polymers (like the transdermal patch), confocal Raman analysis would be used as a replacement for the older, more destructive methods of analysis.

Particularly due to reduced time consumption, this method will hopefully lead to quicker developments and improvements in medication delivery systems.

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This information has been sourced, reviewed and adapted from materials provided by Thermo Fisher Scientific – Materials & Structural Analysis.

For more information on this source, please visit Thermo Fisher Scientific – Materials & Structural Analysis.


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