CAPRYLYL GLYCOL

The present study aims to investigate the current trends in replacing conventional preservatives with multifunctional ingredients with antimicrobial properties for preservation of cosmetics for infants or sensitive population, to decrease their potential for contact dermatitis. We first reviewed the labels of cosmetics purchased from the Chinese market for conventional preservatives and multifunctional ingredients with antimicrobial properties, of which the actual contents were further quantified by chromatographic methods. We identified 7 traditional preservatives (phenoxyethanol, benzoic acid (salts), methylparaben, benzyl alcohol, sorbic acid (salts), propylparaben, and methylisothiazolinone), and 11 alternative ingredients with antimicrobial activities (ethylhexylglycerin, butylene glycol, caprylyl glycol, propylene glycol, 1,2-hexanediol, p-anisic acid, hydroxyacetophenone, pentylene glycol, decylene glycol, caprylhydroxamic acid, and aminomethyl propanol) in descending order of prevalence. The contents of all identified preservatives and ingredients were either below regulatory limits or in the range that is generally regarded to be safe. Further challenge with microorganisms indicated irrespective of the composition of preservation systems, product preservation could be compromised under test conditions. We conclude that multifunctional ingredients with antimicrobial properties in cosmetics have the potential to completely replace or significantly reduce the use of traditional preservatives while retaining comparative preservative efficacy. Future attentions may need to be shifted to the safety of those multifunctional ingredients with antimicrobial properties.

The absence of objectionable micro-organisms in cosmetics and the efficiency of preservatives are still mainly assessed by time-consuming cultivation-based methods. We explored the applicability of real-time quantitative polymerase chain reaction (qPCR) and reported on the behaviour of different bacteria in artificially contaminated creams. Real-time qPCR on DNA from Burkholderia cepacia, Pluribacter gergoviae, Pseudomonas aeruginosa and Sphingomonas paucimobilis identified specific primer pairs that amplify accurately and efficiently two strains/isolates of each species. Using DNeasy mericon Food Kit, we detected bacterial growth in an inoculated cosmetic cream and persistency of DNA from heat-inactivated bacteria. We were also able to monitor the growth inhibitory effect of caprylyl glycol and EDTA, also showing how different bacterial species interact depending on the presence/absence of these ingredients. Finally, creams supplemented with the protective cosmetic ingredients revealed the various behaviour of five strains/isolates from P. aeruginosa. Successfully extracting bacterial DNA from artificially contaminated cosmetic creams, we could perform real-time qPCR to identify and follow the growth of various strains of 4 bacteria species under different conditions. Real-time qPCR appears as a promising method to detect bacterial contamination in cosmetic creams and/or to monitor growth inhibition by ingredients.

The safety assessment of cosmetic products is based on the safety of the ingredients, which requires information on chemical structures, toxicological profiles, and exposure data. Approximately 6% of the population is sensitized to cosmetic ingredients, especially preservatives and fragrances. In this context, the aim of this study was to perform a hazard assessment and risk characterization of benzalkonium chloride (BAC), benzyl alcohol (BA), caprylyl glycol (CG), ethylhexylglycerin (EG), chlorphenesin (CP), dehydroacetic acid (DHA), sodium dehydroacetate (SDH), iodopropynyl butylcarbamate (IPBC), methylchloroisothiazolinone and methylisothiazolinone (MCI/MIT), methylisothiazolinone (MIT), phenoxyethanol (PE), potassium sorbate (PS), and sodium benzoate (SB). Considering the integrated approaches to testing and assessment (IATA) and weight of evidence (WoE) as a decision tree, based on published safety reports. The hazard assessment was composed of a toxicological matrix correlating the toxicity level, defined as low (L), moderate (M), or high (H) and local or systemic exposure, considering the endpoints of skin sensitization, skin irritation, eye irritation, phototoxicity, acute oral toxicity, carcinogenicity, mutagenicity/genotoxicity, and endocrine activity. In a risk assessment approach, most preservatives had a margin of safety (MoS) above 100, except for DHA, SDH, and EG, considering the worst-case scenario (100% dermal absorption). However, isolated data do not set up a safety assessment. It is necessary to carry out a rational risk characterization considering hazard and exposure assessment to estimate the level of risk of an adverse health outcome, based on the concentration in a product, frequency of use, type of product, route of exposure, body surface location, and target population.

An analytical method for the simultaneous determination of phenethyl alcohol, methylpropanediol, phenylpropanol, caprylyl glycol, and ethylhexylglycerin, which are used as alternative preservatives in cosmetic products, has been developed. The method is based on liquid chromatography with UV spectrophotometric detection after chromophoric derivatization with benzoyl chloride and vortex-assisted liquid-liquid semimicroextraction. Different chromatographic parameters, derivatization conditions, and sample preparation variables were studied. Under optimized conditions, the limits of detection values for the analytes ranged from 0.02 to 0.06µgmL(-1). The method was validated with good recovery values (84-118%) and precision values (3.9-9.5%). It was successfully applied to 10 commercially available cosmetic samples. The good analytical features of the proposed method besides of its environmentally-friendly characteristics, make it useful to carry out the quality control of cosmetic products containing the target compounds as preservative agents.

This study describes a new alternative combination preservative containing caprylyl glycol, phenethyl alcohol and glyceryl caprylate and investigates the effects of the particle size of the emulsion droplet on the anti-microbial activity of the said blend in the formulation. The anti-microbial activity of the ingredients and the blend were determined via MIC, MBC, MFC and fractional inhibitory concentration (FIC) determination using the broth microdilution method. The blend inhibited the micro-organism contamination of the oil-in-water emulsion, and its performance was affected by the particle size of the emulsion droplet, as shown by the in vitro microbial challenge test. Results show that the MIC/MBC/MFC values of the blend were lower than those of any of the ingredients used alone. Any two of the ingredients presented no antagonistic activities against all the tested micro-organisms, and synergism or additive effects were also observed. The challenge test also showed that the action of the blend against bacteria and yeast was only 0.3% and 0.2%, respectively, and mould was completely inhibited at 1.4%, meeting the requirements of the PCPC and European Pharmacopoeia. The results showed that anti-microbial activity was gradually enhanced when the particle size of the emulsion droplets increased significantly in the range of 100-900 nm. A positive correlation was found between anti-microbial activity and particle size. The synergistic performance of caprylyl glycol, phenethyl alcohol and glyceryl caprylate and the anti-microbial activity of their blend suggest that their combination is effective and exhibits broad-spectrum anti-microbial activity. Furthermore, the results show a positive correlation between the anti-microbial activity of the preservative and the particle size of the emulsion droplets in the range of 100-900 nm, when the same concentration of the blend is used in the same formulation. The particle size of the emulsion droplets is demonstrated to be a newly discovered factor that influences the preservation of cosmetic products.

Caprylyl glycol and related 1,2-glycols are used mostly as skin and hair conditioning agents and viscosity agents in cosmetic products, and caprylyl glycol and pentylene glycol also function as cosmetic preservatives. The Cosmetic Ingredient Review (CIR) Expert Panel noted that, while these ingredients are dermally absorbed, modeling data predicted decreased skin penetration of longer chain 1,2-glycols. Because the negative oral toxicity data on shorter chain 1,2-glycols and genotoxicity data support the safety of the 1,2-glycols reviewed in this safety assessment, the Panel concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment.

Nanosuspensions are a smart formulation principle for dermal applications, as they increase the penetration of poorly soluble substances into the skin. Because microbial stability is a pre-requisite for dermal formulations, water containing formulations need to be preserved. Preservatives are known to possibly impair the physical stability of disperse systems, i.e. by causing agglomeration. These aggregation phenomena might occur during storage of the final product, but can already occur during the production process itself. Therefore, in this study the influence of six different preservatives on the diminution efficiency during the production of hesperetin nanocrystals was investigated. Particles with and without the addition of preservatives were produced by high pressure homogenization (HPH) and the final particle size was analysed and compared to the non-preserved suspension. All preservatives influenced the diminution progress during production and the final particle sizes obtained. The non-preserved suspension yielded a particle size of about 300 nm. Preservation with Hydrolite, Euxyl PE9010, Rokonsal and Phenonip led to sizes of about 400 nm. Preservation with Caprylyl glycol and MultiEx did not lead to nanoparticles (size > 1 microm) and caused a slight agglomeration of the nanosuspensions. Based on zeta potential measurements it was found that the impairment is related to the lipophilicity of the presverative, i.e. the lower the lipophilicity, the less is the impairment. In conclusion, preservatives impair the diminution efficacy during the production of nanosuspensions. Therefore, if possible, preservatives should be added to nanosuspensions after the production process. If preservatives are required during production, highly hydrophilic preservatives, e.g. Hydrolite E, should be used.

Benzalkonium chloride (BZK), alkyldimethylbenzlamonium chloride, is a cationic surfactant that is used as an antiseptic. BZK is classified as a quaternary ammonium compound composed of molecules of several alkyl chains of differing lengths, that dictate its effectiveness towards different microbes. As a result, BZK has become one of the most used preservatives in antibacterial solutions. Despite its widespread use, it is not clear whether BZK penetrates human skin. To answer this question, BZK treated skin was analyzed using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry imaging. Solutions containing BZK and differing excipients, including citric acid, caprylyl glycol, and vitamin E, were applied ex vivo to excised human skin using Franz diffusion cells. Treated skin was embedded in gelatin and sectioned prior to MALDI-TOF imaging. BZK penetrates through the epidermis and into the dermis, and the penetration depth was significantly altered by pH and additives in tested solutions.

The effect of six different preservatives on the production process and stability of resveratrol nanosuspensions was investigated. Nanosuspensions of the anti-oxidant resveratrol were prepared by high pressure homogenization (1,500 bar, 20 homogenization cycles). The preservatives used were: caprylyl glycol (0.75%), Euxyl PE 9010 (1.0%), Hydrolite-5 (2.0), Phenonip (0.75%), Rokonsal PB-5 (0.5%) and MultiEx Naturotics (2.0%). Preservation is essential for oral and dermal nanosuspensions, but can impair the stability. The effect of the preservatives on stability as a function of cycle numbers was determined by size measurements (photon correlation spectroscopy (PCS), laser diffraction (LD) and light microscopy). Zeta potential measurements were performed for determination of the Stern potential (measurements in water) and as stability criterion (measurements in original dispersion medium), to elucidate the mechanism of destabilization. The preservatives could be placed into three groups. Hydrolite-5 did not affect the production process and the short term stability, sizes were practically identical to the preservative-free nanosuspension (e.g. PCS diameters 196 nm and 184 nm, respectively). All other preservatives impaired the stability medium to pronounced, being most pronounced for MultiEx Naturotics. Hydrolite-5 is recommended as preservative of choice. A mechanistic model was developed to explain the absence and the different degrees of destabilization. In general, when screening for suitable preservatives, suspensions are produced, different preservatives added and the size changes are monitored over long-term. The destabilizing effect of the preservatives on nanosuspensions became evident when added in the production process immediately, thus this can be used as a screening tool for optimal, non-destabilizing preservatives, replacing or minimizing time-consuming long-term stability studies.