Percutaneous absorption of parabens from cosmetic formulations

Absorption through human skin of a series of six p -hydroxy-benzoates (parabens) was studied in vitro. A diffusion chamber was used, where the receiving phase was a physiological solution of albumin. Maximum fluxes and permeability constants of the parabens were measured from different vehicles representing hydrophilic and lipophilic phases, and from different types of common commercial cosmetic emulsions, each containing a known quantity of a single member of the series. Significant skin absorption was observed, depending upon the partition coefficient (log P octanol/water) of the permeant, composition and time of storage of the emulsions. Fluxes from all types of emulsions were higher for methyl paraben and decreased with the increasing lipophilic character of the preservative. Comparatively, fluxes from oil/water emulsions were higher than from water/oil emulsions. Moreover, a clear dependence of preservatives'percutaneous absorption on the time of storage was observed, the fluxes becoming constant after about three months after the time of preparation. The relationship between preservative activity and percutaneous absorption is discussed.     

Transdermal delivery of two antioxidants from different cosmetic formulations

The efficacy of any cosmetic product containing a functional ingredient is determined by the skin delivery of the active molecule, which is influenced by the type of the vehicle and the molecule itself. This study was designed to compare the percutaneous absorption habits of the antioxidants carcinine and lipoic acid out of various formulations by means of the porcine skin model. Initial evaluation of the in vitro porcine skin model has demonstrated its feasibility for various substances and formulations [1, 2]. Increasing legal requirements for risk assessment in the cosmetic industry have led to the development of this alternative test method. The penetration properties are determined by the OECD Guideline TG 428: Skin Absorption: in vitro Method [3, 4], which allows the use of porcine skin for penetration studies. Porcine skin is used because of its similarity to human skin in terms of its morphology and the essential permeation characteristics [5]. The mass balances for each tested formulation type of the antioxidants show individual penetration behaviours with significant differences. The presented data plainly demonstrate that the lipophilic lipoic acid has a distinct higher penetration potential than the hydrophilic carcinine. The chosen vehicle can enhance or reduce the transdermal delivery of both tested antioxidants. Modern effective cosmetic formulations will work only, if the active ingredients penetrate into the epidermis. In conclusion, the correct selection of a suitable formulation plays an important role during product development.     

Predicting skin penetration of actives from complex cosmetic formulations: an evaluation of inter formulation and inter active effects during formulation optimization for transdermal delivery

Twenty products, containing a radiolabelled form of each active in typical cosmetic formulations, were made and applied to female human epidermal membranes mounted in Franz diffusion cells for 48 h under ‘in use’ conditions. The products consisted of combinations of five formulations (a hydro‐alcoholic gel, an oil in water emulsion, a water in oil emulsion, a microemulsion and an oil) with four model drug actives (testosterone, hydrocortisone, 5‐fluorouracil and ketoconazole). Steady‐state flux appeared to be reached by 8 h and maintained for all products, other than for the microemulsions, consistent with the actives being present in the residual formulation on the skin at saturation. The recovery for each active at the end of the 48‐h study (from a series of stratum corneum tape strips, the remaining skin, cumulative amount penetrating into the receptor solution, product washed from the skin and on the donor chamber cap) ranged from 86.5% to 100.6%. The rank order of the fluxes for the actives from the hydro‐alcoholic gel is consistent with the known active molecular size and polarity determinants for maximum epidermal flux. Actives with similar steady‐state (maximum) fluxes from a range of formulations had retention in the stratum corneum and similar transport rate constants through the stratum corneum. The microemulsion formulation significantly enhanced both the stratum corneum steady‐state flux and transport rate constant for 5‐fluorouracil, hydrocortisone and testosterone. The penetration flux of each active could be related to its size and polarity and appeared maximal when the actives in the different cosmetic formulations applied to the skin under ‘in use’ conditions were likely to remain in the residual product on the skin as a saturated solution after solvent evaporation. Enhanced penetration fluxes can be achieved by formulation selection and an appropriate choice/mix of emollients/adjuvants. The principles described here provide a framework for understanding the delivery of cosmetic ingredients from various formulations.     

In vitro skin permeation of sunscreen agents from O/W emulsions

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.     

神经酰胺对皮肤生理作用及其在化妆品中应用

神经酰胺在皮肤角质层中主要作用包括：保湿作用、屏障作用、抗衰老作用和美白作用,这些作用使其成为化妆品重要生物添加剂。该文介绍神经酰胺在化妆品中应用进展,并展望其在化妆品中发展前景。     

In vitro skin permeation evaluation: the only realistic option

Increasing requirements for cruelty-free risk assessment in the cosmetic industry have led to the development of several alternative experimental evaluation strategies. Quantification of the potential dermal absorption of ingredients of cosmetic and other formulations by determination of human skin permeation rates in vitro is particularly relevant. Using modifications of standard in vitro protocols the human skin permeation rates of several cosmetic ingredients and potential contaminants have been determined under conditions designed to mimic consumer use. Skin penetration and permeation of octyl salicylate (a sunscreen), nonylphenol ethoxylates (surfactants) and three nitrosamines (potential contaminants) is discussed. The data demonstrate the usefulness of this technique as a tool in the overall risk assessment of cosmetic formulations.     

Biologically active peptides: from a laboratory bench curiosity to a functional skin care product

Small, biologically active peptides (short sequences of amino acids) were first described about 40 years ago: TRH, angiotensin, vasopressin, oxytocin, bradykinin. Since then, many more peptides have been isolated from mammalian tissue and organs, and their activity investigated. Essentially, these molecules play a hormonal (messenger) role: released at one point in the body, they act at specific receptor sites at different locations in the organism. Mostly the peptides are transported from the site of release to the site of biological activity through the blood or lymphatic fluid. The use of these molecules in cosmetics does not appear obvious, as the topical application of these highly soluble, fragile and extremely expensive molecules seems inappropriate, and systemic effects (blood transport) are not desired. This paper shows that the obstacles to using highly specific, powerful peptides as 'actives' in cosmetic products can be overcome. Cosmetically interesting activities such as stimulation of collagen synthesis, chemotaxis, anti-stinging effects and others, can be observed and substantiated with chemically modified peptide sequences. Long chain fatty acid conjugates improve skin penetration, specific activity and economic feasibility of these molecules.     

Anti-irritant potential of cosmetic raw materials and formulations

The investigation studied the anti-irritant potential of several substances commonly employed in cosmetic formulations as basic components of the emulsion or as active ingredients, and evaluated the effect of the emulsifier. Five different emulsions were made irritating by addition of croton oil, in sufficient quantity to provoke a clearly adverse reaction in the rabbit, i.e. primary cutaneous irritation index (PII) close to 2. The PII was determined according to the official French methods by applying to symmetrical areas of the back, the irritant base as control and the same base containing the test substance. Fifty-five ingredients were evaluated: gelling agents, plant extracts, molecules defined as healing, anti-inflammatory substances or anaesthesic compounds, etc. The test substances were added to the emulsion at concentrations close to the ones generally found in cosmetics. The qualitative and the quantitative composition of the oil phase was similar for each emulsion.
Several gelling agents, thickeners and polymers which notably reduce skin contact with an irritant, gave good results. Some of the usual healing, anti-inflammatory, local anaesthesic compounds gave the expected results. Some ingredients, though well known, were ineffective. The type of emulsifier, by modifying cutaneous penetration and bio-availability of the active ingredients, may play an important role.
Le potential anti-irritant de constituants de base et compositions cosmétiques