Confocal Raman Spectroscopic Imaging for Evaluation of Distribution of Nano-Formulated Hydrophobic Active Cosmetic Ingredients in Hydrophilic Films

Abstract

Film-forming systems are highly relevant to the topical administration of active ingredients (AI) to the body. Enhanced contact with the skin can increase the efficacy of delivery and penetration during prolonged exposure. However, after the evaporation of volatile solvents to form a thin film, the distribution of the ingredient should remain homogenous in order to ensure the effectiveness of the formula. This is especially critical for the use of hydrophobic molecules that have poor solubility in hydrophilic films. In order to address this concern, hydroxyphenethyl esters (PHE) of Punica granatum seed oil were prepared as a nanosuspension stabilised by poloxamers (NanoPHE). NanoPHE was then added to a formulation containing polyvinyl alcohol (PVA) as a film forming agent, Glycerol as a plasticiser and an antimicrobial agent, SepicideTM HB. Despite their reliability, reference methods such as high-performance liquid chromatography are increasingly challenged due to the need for consumables and solvents, which is contrary to current concerns about green industry in the cosmetics field. Moreover, such methods fail to provide spatially resolved chemical information. In order to investigate the distribution of ingredients in the dried film, Confocal Raman imaging (CRI) coupled to Non-negatively Constrained Least Squares (NCLS) analysis was used. The reconstructed heat maps from a range of films containing systematically varying PHE concentrations highlighted the changes in spectral contribution from each of the ingredients. First, using NCLS scores it was demonstrated that the distributions of PVA, Glycerol, SepicideTM HB and PHE were homogenous, with respective relative standard deviations (RSD) of 3.33%, 2.48%, 2.72% and 6.27%. Second, the respective relationships between ingredient concentrations in the films and their Raman responses, and the spectral abundance were established. Finally, a model for absolute quantification for PHE was be constructed using the percentage of spectral abundance. The prepared %w/w concentrations regressed against predicted %w/w concentrations, displaying high correlation (R2 = 0.995), while the Root Mean Squared Error (0.0869% w/w PHE) confirmed the precision of the analysis. The mean percent relative error of 3.75% indicates the accuracy to which the concentration in dried films could be determined, further supporting the suitability of CRI for analysis of composite solid film matrix. Ultimately, it was demonstrated that nanoformulation of hydrophobic PHE provides homogenous distribution in PVA based film-forming systems independent of the concentration of NanoPHE used in the formula.

Microemulsion Delivery Systems with Low Surfactant Concentrations: Optimization of Structure and Properties by Glycol Cosurfactants

“…The band at 1654 cm –1 may arise from very strong C=C stretching (unsaturated hydrophobic tail of surfactants). 25 The bands observed at 2743 and 2736 cm –1 can be attributed to CH 2 , and bands in the range of 2850–2950 cm –1 are assigned to the aromatic C–H. 25 However, no characteristic band for water was observed on the Raman spectrum, i.e., the O–H stretching, which produces a broad band in the range of 3100–3650 cm –1 .…”

“… 25 The bands observed at 2743 and 2736 cm –1 can be attributed to CH 2 , and bands in the range of 2850–2950 cm –1 are assigned to the aromatic C–H. 25 However, no characteristic band for water was observed on the Raman spectrum, i.e., the O–H stretching, which produces a broad band in the range of 3100–3650 cm –1 . However, it should be taken into account that water molecules in MEs can strongly interact with polar groups of surfactants and with glycols, especially with very hydrophilic PG.…”

Novel aspects of Raman spectroscopy in skin research

“…for glycolic acid, Punica granatum seed oil hydroxyphenethyl ester [PHE] and raspberry seed oil). [144][145][146][147] Effects of glycolic acid on the skin were assessed by measurement of biophysical skin parameters in in vivo studies (5-h, 4-h and 7-day).…”

“…In addition to penetration studies, Raman spectroscopy is also used in formulation studies (e.g. for glycolic acid, Punica granatum seed oil hydroxyphenethyl ester [PHE] and raspberry seed oil) 144‐147 . Effects of glycolic acid on the skin were assessed by measurement of biophysical skin parameters in in vivo studies (5‐h, 4‐h and 7‐day).…”

Monitoring Dermal Penetration and Permeation Kinetics of Topical Products; the Role of Raman Microspectroscopy

“…However, for the comparison of products, the equivalence parameters of drug uptake and clearance, could conceivably be compared, in situ. As an example, Essendoubi et al used MCR-ALS for the analysis of CRM penetration profiles of free and an encapsulated form of retinol in sections of frozen and living tissue, demonstrating a higher permeation efficiency of the encapsulated form [89], and a number of further studies have used CRM to monitor the penetration of nanoformulations [90,91].…”