Research

Research on the Penetration of Caffeine and Propylene Glycol by Confocal Raman Spectroscopy

 2024.10.9.

Propylene glycol is an organic alcohol, often used as one of the penetration enhancers and also employed as a humectant, viscosity decreased agent, solvent and fragrance ingredient.

We determined penetration depth value using confocal Raman microscopies combined with the multivariate statistical methods and compared the results obtained from different confocal Raman microscopies.

A suspension of caffeine in water, ethanol, and 1,2-propylene glycol mixture containing Carbopol 981 as stabilizer for the crystals was prepared. This suspension was milled in the chamber, using power beads with a size of 0.4-0.6mm, operating condition 2 000rpm of the agitator at 5℃ production temperature. Size measurements of the nanocrystals were performed by photon correlation spectroscopy (PCS) using a Zetasizer ZS Nano(Malvern Instruments, UK).

Short term stability conducted at a storage temperature of 4℃ showed stability over 30 days, no significant change in PCS size, and the absence of aggregates.

Figure. Raman spectra of cream formulation (black), the untreated porcine skin at the depth 4µm (pink), the treated porcine skin at the depth 4µm (green) and caffeine (red) and PG (propylene glycol) (blue) measured using CRM "Horiba" (excitation 633 nm)

As shown in the figure the spectral ranges 526-600 and 770-980 cm-1 show the prominent differences between caffeine crystal and porcine skin. More importantly the peak 556cm-1 of caffeine, (CON deformation mode, REF) and 840cm-1 of PG (propylene glycol) ((C-O)H stretching mode, REF) shows the no overlapping with the spectra of the untreated skin.

Peaks between 780 cm-1 and 980 cm-1, was detected for the caffeine gel-treated porcine skin and penetration depths were measured. The result showed that the penetration depth of caffeine is different from that of propylene glycol which, as a penetration enhancer, penetrates 2.6μm more when their mixture is applied to skin with gel.

This research was published on JOURNAL OF BIOPHOTONICS under the title of "Quantification of skin penetration of caffeine and propylene glycol applied topically in a mixture by tMCR-ALS chemometric analysis of Confocal Raman spectroscopy" (https://doi.org/10.1002/jbio.202300146).