CETEARYL GLUCOSIDE

Alkyl glucosides contitute a family of mild surfactants that are increasingly being used in a wide range of cosmetics and household products. Contact allergy to alkyl glucosides may be more frequent than previously suspected, especially in atopic patients. To investigate the frequency of contact allergy to alkyl glucosides, and to identify concomitant reactivity. We retrospectively reviewed all cases of suspected allergic contact dermatitis (ACD) in which patients were patch tested with either a cosmetic series that includes five alkyl glucosides (decyl glucoside, lauryl glucoside, coco glucoside, cetearyl glucoside, and caprylyl/capryl glucoside) or a specific alkyl glucoside series from November 2013 to April 2017 in two UK centres. A total of 5775 patients were patch tested across the two centres. Twenty-nine (1.04%) of the 2796 patients tested with the cosmetic/alkyl glucoside series had a positive patch test reaction to at least one of the alkyl glucosides. Twenty-three (79.3%) patients were sensitized to multiple alkyl glucosides; 21 patients (72.4%) were female. The mean age was 43.5 years. Twelve patients (41.4%) had a background of atopic dermatitis. The prevalence of alkyl glucoside-induced ACD is relatively high, and there are frequent concomitant reactions between different alkyl glucosides. We recommend the inclusion of alkyl glucosides in all cosmetic series.

Alkyl glucosides were not expected to have a sensitizing potential at the concentrations to be used in finished consumer products; however, several contact allergy cases have been published. To report on the patients suffering from allergic contact dermatitis caused by alkyl glucosides observed in our department. During a 19-year period (1993-2012), 11 842 patients with suspected contact dermatitis were patch tested with the European baseline series and, if relevant, also with other series and individual allergens. For this study, the clinical data and the sensitization sources in the alkyl glucoside-positive patients were analysed. In total, 30 patients (24 women and 6 men) presented with a positive reaction to one or more alkyl glucosides. The causal products were shampoos (in 12), skin-cleansing products (in 12, among which were wipes for intimate hygiene), sunscreen products (in 5), skin-care products (in 4), and a deodorant (in 1). Sixteen patients showed multiple sensitivities (defined as three or more contact allergies), not only to other glucosides, but also to non-related chemicals. Allergic contact dermatitis caused by alkyl glucosides in cosmetics does occur, and might be more frequent than suspected. In view of their common use, their identification as allergenic culprits is important.

This study investigates the application of D-optimal mixture experimental design in optimization of O/W cosmetic emulsions. Cetearyl glucoside was used as a natural, biodegradable non-ionic emulsifier in the relatively low concentration (1%), and the mixture of co-emulsifiers (stearic acid, cetyl alcohol, stearyl alcohol and glyceryl stearate) was used to stabilize the formulations. To determine the optimal composition of co-emulsifiers mixture, D-optimal mixture experimental design was used. Prepared emulsions were characterized with rheological measurements, centrifugation test, specific conductivity and pH value measurements. All prepared samples appeared as white and homogenous creams, except for one homogenous and viscous lotion co-stabilized by stearic acid alone. Centrifugation testing revealed some phase separation only in the case of sample co-stabilized using glyceryl stearate alone. The obtained pH values indicated that all samples expressed mild acid value acceptable for cosmetic preparations. Specific conductivity values are attributed to the multiple phases O/W emulsions with high percentages of fixed water. Results of the rheological measurements have shown that the investigated samples exhibited non-Newtonian thixotropic behaviour. To determine the influence of each of the co-emulsifiers on emulsions properties, the obtained results were evaluated by the means of statistical analysis (ANOVA test). On the basis of comparison of statistical parameters for each of the studied responses, mixture reduced quadratic model was selected over the linear model implying that interactions between co-emulsifiers play the significant role in overall influence of co-emulsifiers on emulsions properties. Glyceryl stearate was found to be the dominant co-emulsifier affecting emulsions properties. Interactions between the glyceryl stearate and other co-emulsifiers were also found to significantly influence emulsions properties. These findings are especially important as they can be used for development of the product that meets users' requirements, as represented in the study.

Approaching of pharmaceutical and cosmetic industries in some aspects inevitably influence formulation of topical pharmaceuticals, urging researchers to introduce novel excipients with proven benefits over traditional ones. In that context, alkyl polyglucosides (APG) emerge as prominent natural-origin emulsifiers with numerous favorable features (biodegradability, dermatological acceptability, desirable sensory properties). To evaluate APG-stabilized bases (alone and upon addition of isopropyl alcohol) and their impact on skin performance. A simultaneous in vitro/in vivo skin absorption study was conducted to evaluate whether the tape stripping technique could be recommended as an in vivo tool for skin penetration assessment during formulation optimization process. After a comprehensive physicochemical characterization, biopharmaceutical properties of APG-bases versus reference ones were assessed through a combined in vitro (release/permeation) and in vivo approach. Physicochemical characterization revealed substantial difference in structural ordering due to the formation of various mesomorphic phases. The enhancer-loaded APG base resulted in significantly higher drug levels at all depths into the stratum corneum, indicating that the selected enhancer along with specific colloidal structure has increased the extent of drug delivery. Results recommend the investigated emulsifier for stabilization of topical drug delivery systems, not only for their ability to sustain the addition of isopropyl alcohol which proved to be a valuable enhancer, but also satisfactory skin absorption and tolerability when compared to samples stabilized by conventional emulsifier. Tape stripping proved to be a useful and yet inexpensive tool for in vivo trials, able to discriminate subtle differences in dermal availability.

The barrier function of the stratum corneum (SC) significantly determines the interaction of epicutaneously applied substances with the skin organ. Although the exact molecular processes are still unclear, it is undoubted that the intercellular lipid composition and order of the SC is significantly involved in this interaction. Topically substituted phases, especially those of lipophilic composition, seem to interact very intensely with lipid membranes; they can be integrated, form separate phases, or even permeate through the SC into the viable skin. The latter is not desired, especially in barrier-protective preparations with a lipophilic phase. The present paper investigates the penetration behavior of topically applied, DiI-labeled lipids into human ex vivo skin depending on the phase organization of different o/w emulsifiers compared to emulsifier-free preparations containing hydrogenated phosphatidylcholine by means of fluorescence indication. Results are presented for intact and defined damaged epidermal barrier. In addition, the washout effect based on skin samples treated by artificial watering after lipid incubation, and the influence of the phase transition temperature of the SC membrane were studied. The results show that in intact and damaged skin, the penetration depth of the lipids increases directly proportionally with the hydrophilic-lipophilic balance (HLB value), while the washout effect and the HLB value proved to be inversely related. An increase in penetration depth with higher HLB values was also apparent when the phase transition temperature of the physiological membranes was exceeded. Altogether, the results clearly demonstrate that the characteristics of the emulsifying phase of a preparation significantly determine the interaction of a substituted lipophilic phase with the SC. Especially bipolar lipids, like phosphatidylcholines, showed intradermal dispersion patterns which hint at an especially intense interaction with physiological membranes.

This study focuses on the properties of topical vehicles based on alkylpolyglucoside natural surfactant-mixed emulsifier, cetearyl glucoside and cetearyl alcohol, in order to propose their use as "ready to use" pharmaceutical bases for a number of model drugs. We were interested to investigate how the alternative use of three lipophilic excipients (Ph. Eur. 6.0), differing in their polarity indexes (medium chain triglycerides (MG), decyl oleate (DO), and isopropyl myristate (IPM), respectively), affects the colloidal structure of the alkylpolyglucoside-based vehicles and in vitro permeation profiles of two model drugs: diclofenac sodium (DC) and caffeine (CF), both sparingly soluble in water. Finally, we aimed to evaluate the safety profile of such vehicles in vitro (acute skin irritation test using a cytotoxicity assay), comparing it with in vivo data obtained by the methods of skin bioengineering. The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. Varying of lipophilic excipient influenced noteworthy variations in the colloidal structure demonstrated as different rheological profiles accompanied to the certain degree by different water distribution modes, but notably provoked by drug nature (an amphiphilic electrolyte drug vs. nonelectrolyte). In vitro permeation data obtained using ASC membranes in an infinite dose-type of experiment stressed the importance of the vehicle/solute interactions in case of small variation in formulation composition, asserting the drug properties in the first hours of permeation and rheological profile of the vehicles in the later phase of experiment as decisive factors. In vitro skin irritation test demonstrated a mild nature of the emulsifying wax and the absence of negative effects of used oil phases on cell viability in formulation concentrations correspondent to the therapeutic need. This result alongside with data obtained from in vivo study, could additionally promote investigated topical vehicles as prospective "ready to use" pharmaceutical bases.

There is a growing need for in-depth research into new skin- and environment-friendly surfactants, such as alkylpolyglucosides. The aim of this study was to assess whether, to which extent and by what mechanism the two commonly used hydrophilic excipients, propylene glycol (PG) and glycerol (GL), affect the colloidal structure of emulsions formed by a natural mixed emulsifier, cetearyl glucoside and cetearyl alcohol. Furthermore, the study was concerned with the effect of these changes on in vitro permeation profiles of two model drugs (diclofenac sodium and caffeine) and in vivo skin performance of the test samples. The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. PG addition produced a stronger hydrophilic lamellar gel phase than GL, which was independent on the model drug used. PG-containing vehicles have revealed a considerable amount of interlamellar PG/water mixture, with incorporated drug. In vitro permeation data obtained using artificial skin constructs (ASC) confirmed the relationship between rheological profiles of vehicles and the extent of skin delivery. Higher permeation profiles of both drugs from PG-containing formulations coincided with a higher increase in transepidermal water loss observed in in vivo study on human volunteers, which confirms the penetration/permeation enhancer effect of PG. It also indicates the existence of the vehicle/ASC interactions analogous to those between the vehicle and the skin, thus affirming the use of ASC as a reliable tool for permeation studies. Contrary to the effect of PG, the results obtained with GL suggest that it may have a permeation-retarding rather than a permeation-enhancing effect in topical vehicles of this type.

The effects of different emulsifiers on the in vitro permeation through human skin of two sunscreen agents [octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM)] were investigated from O/W emulsions. The test formulations were prepared using the same oil and aqueous phase ingredients and the following emulsifier and coemulsifier systems: Emulgade SE((R)) (ceteareth-12 and ceteareth-20 and cetearyl alcohol and cetyl palmitate) and glycerylmonostearate (emulsion 1); Brij 72((R)) (steareth-2), Brij 721((R)) (steareth-21) and cetearyl alcohol (emulsion 2); Phytocream((R)) (potassium palmitoyl-hydrolysed wheat protein and glyceryl stearate and cetearyl alcohol) and glycerylmonostearate (emulsion 3); Montanov 68((R)) (cetearyl glucoside and cetearyl alcohol) (emulsion 4); Xalifin-15((R)) (C(15-20) acid PEG-8 ester) and cetearyl alcohol (emulsion 5). The cumulative amount of OMC that permeated in vitro through human skin after 22 h from the formulations being tested decreased in the order 3 > 1 congruent with 4 > 5 > 2 and was about nine-fold higher from emulsion 3 compared with that from emulsion 2. As regards BMBM, no significant difference was observed as regards its skin permeation from emulsions 1, 3, 4 and 5, whereas formulation 2 allowed significantly lower amounts of BMBM to permeate the skin. In vitro release experiments of OMC and BMBM from emulsions 1-6 through cellulose acetate membranes showed that only emulsions 4 and 5 provided pseudo-first-order release rates only for OMC. The results of this study suggest that the type of emulsifying systems used to prepare an O/W emulsion may strongly affect sunscreen skin permeation from these formulations. Therefore, the vehicle effects should be carefully considered in the formulation of sunscreen products.