Preserving the faith A cosmetic formulators overview John Woodruff www.creative-developments.co.uk John Woodruff: the personal stuff
1960: joined Smith & Nephew Research 1976: Co-founded Pava, responsible for all technical aspects, from formulation and development to manufacture and filling and originated many well-known brands. October 1988: Established consulting laboratory for formulation of cosmetics and toiletry products. Developed Creativity a unique programme written for formula creation and cosmetic manufacture Two books and many articles published on cosmetic technology. Twice appeared as an expert witness, 3 times Chairman of the European UV & Sun Filters Conference, Twice chaired a technical session at In-Cosmetics 1990 – 1996: Cosmetics Consultant to Manufacturing Chemist 1996 – Present: Regular contributions to Soap, Perfumery and Cosmetics (SPC) Supports the Distance Leaning Course run by the SCS Lectures on product formulation at the Principles and Practice of Cosmetic Science When he is not working he is sailing.
2 The cosmetic product brief
• Product type • Claims • Product format • Application • Texture • Colour • Perfume • Packaging • Cost
3 What about the preservative?
Preservatives are one of the last things that most chemists think about when formulating a product and one of the first things that are suspected when a problem occurs. They are important ingredients, the value of which is never noticed when functioning properly and which are worthless when not. Preservatives are much maligned and misunderstood within the cosmetics industry. Because of this, they are often over-dosed, under-dosed or improperly formulated even by experienced chemists Cosmetic formulations require a delicate balance of a large number of raw materials. The preservative system should be among those materials considered when developing a new formula, not an afterthought
Schϋlke • http://www.cosmetic-preservation.com/ 4 The legal stuff EU Cosmetics Regulation (EC) No. 1223/2009
Cosmetics must be resistant to microbial contamination Preservative efficacy must be assessed experimentally to ensure microbial stability and preservation during storage and use SCCS/1501/12 gives guidance for the testing of cosmetic substances and includes guidelines on microbiological quality of the finished cosmetic product For cosmetics sold in Europe (EC) No. 1223/2009 lists a table of permitted preservatives as Annex V This list was first compiled in 1982 and more than half are not in general use and there have only been two new ones added in the last decade The prohibitive cost of gaining acceptance for any new ones will severely restrict any future additions
5 The problem
A presentation from Inolex, Cosmetic Preservation, Market Review, makes the very valid point that the internet gives voice to all, regardless of qualification and that …… “Real science” and “Junk science” are given the same credibility by an ill- informed public Consumer, environmental and political groups are capitalising on this to move their cause forward And so are cosmetic companies And ingredient suppliers
6 The result
For various reasons consumers do not like preservatives in general and parabens in particular; this makes cosmetic preservation even more difficult
“The limited number of available preservatives increases the risk of developing resistant strains of bacteria. It also increases the risk that consumers will develop allergic reactions to the preservative and a diverse palette is needed” Valérie Murset of the *EFfCI
“The biggest issue confronting the preservative market is the potential for misinformation to impact a formulator’s choice in product preservation and imperil consumers” Mark Miller, McIntyre
*EFfCI - European Federation for Cosmetic Ingredients
7 The formulators challenge
Stay legal in all potential markets lack of harmonisation between EU, USA, Japan, Brazil, Australia etc. Please the marketing department who are trying to please consumers Provide adequate preservation throughout the life of the product shelf life period after opening Watch out for next consumer or legislative target • Isopropylparaben, isobutylparaben, phenylparaben, benzylparaben and pentylparaben now banned • Maximum concentration of propylparaben and butylparaben reduced from 0.4% when used individually and 0.8% when mixed with other esters, to 0.14% when used individually or together – early 2015 • MCI/MI mix banned from leave-on products such as body creams July 2015 • Will methylisothiazolinone be next?
8 The formulators frustrations
Parabens work but consumer perception is that they are “bad” Organic acids do not work well but consumer perception is that they are “good” Consumer perception is that chemicals are “bad” and petrochemicals are even worse yet benzyl alcohol is good. Also if benzyl alcohol is part of a perfume it is a potential allergen at 0.001% yet can be used as a preservative at up to 1% Other materials that have this anomalous behaviour includes salicylic acid: listed in Annex V to be used at a maximum concentration of 0.5% as a preservative however it is permitted at 3% in rinse-off hair products and 2% in leave-on skin care with the provision that its primary purpose must not be the inhibition of micro-organisms and its purpose must be apparent from the presentation of the product!
9 The formulators frustrations
What is good in Europe becomes bad in the USA or Japan etc. and visa –versa
Example: o-cymen-5-ol is closely related to thymol, which occurs naturally in many plants including thyme, where it may represent 60% of its essential oil
Annex V: permitted at up to 0.1% in leave-on and wash-off products
The CIR Review shows it as safe at concentrations up to 0.5%
No upper limit in Japan provided the product is not intended for use on mucous membranes. Perhaps we should add 1% thyme oil to our products. Many essential oils have antimicrobial activity and suppliers are creating interesting mixtures that circumvent Annex V
10 Some answers
Convince the consumer that preservatives protect them from potential harm
Make products anhydrous
Formulate the product to provide an unfriendly environment to bacteria, yeasts and moulds
Use permitted preservatives
Look for synergy between preservatives
Use materials that coincidently have an antimicrobial action
11 Convince the consumer
• Present the facts Scientific opinions by the SCCS and CIR reports The CTPA simplifies reports and presents www.thefactsabout.co.uk/ The Personal Care Products Council www.cosmeticsinfo.org/ Cosmetics Europe www.cosmeticseurope.eu/ Chemical Watch https://chemicalwatch.com/ First convince the marketing department Then convince beauty editors Then educate the consumer
12 Make products anhydrous
Lipsticks and pressed powders
Seal from the environment – aerosols; collapsible tubes; certain pump dispensers
Powdered shampoos
Non-aqueous shower gels & bath additives
Solvent-based products e.g. Mascara; After-shave; Toilet Waters
13 Unfriendly environments: a.k.a. Hurdle technology
Reduce water availability Lowering the water activity of the final composition is a possible route to avoid the use of traditional preservatives however it is rarely practical with an oil-in- water composition or with other water-based products Materials used to achieve lower water activity include glycols such as glycerin and butylene and propylene glycols Higher diols like pentylene glycol, 1,2-hexanadiol and caprylyl glycol appear to have an antimicrobial effect beyond their water-binding capacity but they also become less water-soluble Unfriendly pH Preservative-free & self-preserving cosmetics & drugs; Jon J Kabara, Donald S Orth
14 Use permitted preservatives
(EC) No. 1223/2009 Annex V- permitted preservatives
Benzoic acid and its sodium salt Glutaral 2-Bromo-2-nitropropane-1,3- diol (Bronopol) Hexamidine & salts 5-Bromo-5-nitro-1,3-dioxane Hexetidine 7-Ethylbicyclooxazolidine Imidazolidinyl urea Benzalkonium chloride, bromide etc Iodopropynyl butylcarbamate Benzethonium Chloride Kathon CG Mix Benzyl alcohol Methenamine Benzylhemiformal Methylisothiazolinone Biphenyl-2-ol, and its salts o-Cymen-5-ol Bromochlorophene o-Phenylphenol, sodium o-phenylphenatae etc Cetrimonium Chloride etc Parabens Chlorhexidine, Chlorhexidine diacetate p-Chloro-m-Cresol Chloroacetamide Phenoxyethanol Chlorobutanol Phenoxyisopropanol Chlorophene Phenylmercuric salts Chlorophene Piroctone Olamine Chloroxylenol Polyaminopropyl biguanide Chlorphenesin Propionic acid + salts Climbazole Quaternium-15 Dehydroacetic acid, sodium dehydroacetate Silver chloride Diazolidine urea Sodium Hydroxymethylglycinate Dibromohexamidine Isethionate Sorbic acid and sorbates Dichlorobenzyl Alcohol Sulfites Dimethyl Oxazolidine Thimerosal DMDM Hydantoin Triclocarban Formaldehyde, Paraformaldehyde Triclosan Formic acid, sodium formate Undecylenic acid and its salts Zinc pyrithione
15 Annex V Simplified. 54 ingredients plus salts Useful permitted preservatives
Benzoic acid and its sodium salt Iodopropynyl butylcarbamate 2-Bromo-2-nitropropane-1,3- diol MIC/MI mix Chlorhexidine, Chlorhexidine diacetate Methylisothiazolinone Chloroacetamide o-Cymen-5-ol Chlorophene Parabens Chloroxylenol p-Chloro-m-Cresol Chlorphenesin Phenoxyethanol Dehydroacetic acid, Na dehydroacetate Phenoxyisopropanol Diazolidine urea Polyaminopropyl biguanide Dichlorobenzyl alcohol Quaternium-15 DMDM Hydantoin Silver chloride Glutaral Sodium Hydroxymethylglycinate Sorbic acid and sorbates Undecylenic acid + salts Annex V Very Simplified. 26 ingredients plus salts 16 Useful permitted preservatives
Benzoic acid & Na benzoate (0.5% in Iodopropynyl butylcarbamate Leave-on) 2-Bromo-2-nitropropane-1,3- diol MIC/MI Mix Chlorhexidine, Chlorhexidine diacetate Methylisothiazolinone Chloroacetamide o-Cymen-5-ol Chlorophene Parabens Chloroxylenol p-Chloro-m-Cresol Chlorphenesin (0.3%) Phenoxyethanol (1.0%) Dehydroacetic acid, Na Phenoxyisopropanol [Rinse-off only] dehydroacetate (0.6%) Diazolidine urea Polyaminopropyl biguanide Dichlorobenzyl Alcohol (0.15%) Quaternium-15 DMDM Hydantoin Silver chloride Glutaral Sodium Hydroxymethylglycinate Sorbic acid and sorbates (0.6% as acid) Imidazolidinyl urea Undecylenic acid & salts (0.2% as acid) Annex V Very Very Simplified 17 COSMOS permitted preservatives
Benzoic acid & its salts pH & solubility problems Benzyl alcohol Known allergen Salicylic acid & its salts pH & solubility problems Sorbic acid & its salts pH & solubility problems Dehydroacetic acid & its salts pH problems
18 Frequency of Use: List prepared by US 2007 US 2010 Canada Canada David Steinberg showing numbers of products containing preservatives as shown 2008 2010 Methylparaben 25.38% 22.53% 25.71% 25.39% Propylparaben 20.40% 17.48% 22.27% 15.83% Phenoxyethanol 11.22% 14.89% 12.71% 15.83% Butylparaben 9.72% 8.87% 9.06% 9.50% Ethylparaben 8.28% 8.17% 8.02% 8.60% Isobutylparaben 3.68% 4.52% 4.23% 0.25% MI 3.08% 4.04% 2.24% 4.21% MCI/MI mix 3.04% 3.75% 1.52% 3.92% DMDM Hydantoin 3.64% 3.41% 3.22% 3.45% Imidazolidinyl urea 4.95% 3.37% 4.45% 3.72% Benzyl Alcohol 2.46% 3.34% 1.98% 2.95% Caprylyl Glycol 1.29% 2.87% 0.62% 2.07% Diazolidinyl urea 2.84% 2.76% 3.96% 4.28%
Preservatives in common use in USA & Canada 19 Frequency of Use: List prepared by David Steinberg showing numbers of products Can Cana containing preservatives as shown US 2007 US 2010 2008 2010 Parabens 67.47% 61.57% 69.29% 59.57%
Formaldehyde Donors 11.43% 9.54% 11.64% 11.45%
Phenoxyethanol 11.22% 14.89% 12.71% 15.83%
MCI + MCI/MI mix 6.12% 7.79% 3.76% 8.13%
Benzyl Alcohol 2.46% 3.34% 1.98% 2.95%
Caprylyl Glycol 1.29% 2.87% 0.62% 2.07%
Simplified by preservative types 20 Trends in preservative use: USA 2007 - 2010
16.00% Phenoxyethanol 14.00%
12.00%
10.00% Formaldehyde donors
8.00%
6.00% MCI + MI + MCI
4.00% Benzyl alcohol
2.00% Caprylyl glycol
0.00% 1 2
21 Trends in preservative use in EU
European skin 2009 2010 2011 2012 2013 2014 care Benzoates 6.89% 5.77% 13.00% 13.34% 13.67% 13.59%
Isothiazolines 0.00% 0.01% 0.07% 0.29% 0.26% 0.29%
Parabens 63.15% 63.37% 61.43% 61.39% 61.32% 61.35%
Phenoxyethanol 29.96% 30.85% 25.50% 24.98% 24.75% 24.78%
22 Trends in European preservative use 35.00%
30.00% Phenoxyethanol 25.00%
20.00%
15.00% Benzoic acid/Benzoates
10.00%
5.00% Isothiazolines 0.00% 1 2 3 4 5 6
Benzoates Isothiazolines Phenoxyethanol
Parabens make up the difference @ ~ 61%
23
Permitted preservatives: improve effect
• Activity of parabens increases with the increase in alkyl chain length, however their solubility in water is inversely proportional to the length of alkyl chain
• Methylparaben is only soluble at 0.25% in water –
• If oils are present its partition coefficient will favour migration into the oil phase but adding 0.02% propylparaben to the emulsion keeps methylparaben in the aqueous phase
• 2% propylene glycol allows the minimum inhibitory concentration of methylparaben to be reduced from 0.18% to 0.1% when combined with 0.02% propylparaben • Prickett PS, Murray HL, Mercer NH. Potentiation of preservatives (parabens) in pharmaceutical formulations by low concentrations of propylene glycol. J Pharm Sci 1961; 50: 316–320
25 Permitted preservatives: improve effect
• Phenoxyethanol is a favoured solvent for parabens • Other materials that enhance activity by promoting solubility are • benzyl alcohol • Ethylhexylglycerin • Ethanol • 1,2 Hexanediol is a solvent that enhances the preservative potency of known mild preservatives • these materials plus propylene glycol frequently appear in preservative systems offered as alternatives to parabens because of their antimicrobial activity and solvent properties
26 Improving the effect: Phenoxyethanol
Phenoxyethanol is permitted to a maximum level of 1% and has bactericidal activity across the total pH range likely to be found in cosmetics
Best against Gram –ve bacteria; weak activity against other microbial contaminants so it is usually found in combination with other preservatives; traditionally parabens but other mixtures are now widely available
Its solubility in water is about 2.4%
It is compatible with cationic and anionic surfactants but it may be inactivated by ethoxylated surfactants
Increasingly popular but does not have COSMOS or Ecocert approval
27 Improving the effect: Benzyl alcohol
Benzyl alcohol is approved as a preservative in EU at a maximum level of 1% Water soluble up to about 3g/L and is bactericidal at between 1% and 2% OK against Gram +ve; some activity against Gram –ve & yeast; poor against mould Optimum pH <5; little effect above pH 7. Inactivated by non-ionics Good as solvent for parabens It is often used in perfumery as a solvent but because it is a potential irritant its presence must be indicated on the label when its concentration exceeds 0.001 % in leave-on products and 0.01 % in rinse-off products The anomaly is that despite these concerns it can be used above 1% for purposes other than inhibiting the development of microorganisms but this purpose has to be apparent from the presentation of the product
28 Improving the effect: Ethylhexylglycerin
Ethylhexylglycerin has no restrictions under current EU legislation
It is a weak preservative in its own right. It works by reducing interfacial tension on the cellular walls of micro-organisms, enhancing the effect of other preservatives by increasing their penetration through the cell membrane
Its HLB is approximately 7.5 and this can upset some emulsifier systems
Its water solubility is about 1.8g/L but it is soluble to about 30% in propylene glycol
Interestingly it has demonstrable emollient properties and is increasingly used as a multifunctional component in preservative mixtures
It shows minimal dermal penetration
29 Use organic acids
Table by Courtesy of Inolex: CHA is caprylhydroxamic acid • .
CHA is the only organic acid with significant antimicrobial activity at pH 7. CHA is also a powerful chelating agent for iron
30 Organic acids
Generally the activity of organic acids is not wide spectrum and their efficacy is very pH dependent Benzoic acid is effective at a concentration of 0.1% to 0.3%, which is the limit of its solubility in water. Its pKa = 4.19 and it is ineffective in solutions with a pH above 5 Because of its insolubility in water it is often used as the very soluble sodium salt but its effectiveness may be reduced by non-ionic surfactants such as the polysorbates Widely available in mixtures with other organic acids and phenoxyethanol and/or ethylhexylglycerin and/or benzyl alcohol Sorbic acid - effective concentration of 0.05% to 0.2% that is very close to its limit of solubility so potassium sorbate is often used Sorbic acid may be used at a higher pH than benzoic acid but is said to have little antimicrobial activity above pH 6 Commonly used in mixtures
31 Organic acids
Dehydroacetic acid is permitted to 0.60% but is almost insoluble in water (≥0.1%) however it remains effective to pH 6 Salicylic acid is permitted to 0.50% and may be used at higher levels if its primary purpose is not as a preservative e.g. Anti-acne and exfoliating products* • Effective antifungal and better antimicrobial properties than benzoic acid • It is soluble in water to about 0.2% effectiveness declines rapidly above pH 2 • Mostly found in mixtures: *It is the opinion of the SCCNFP that those substances in Annex V, that when incorporated into cosmetic formulations for non-preservative functions, should be subjected to the same restrictions in usage levels and warnings as when used for preservative effect This opinion is widely ignored *Scientific Committee on Cosmetic Products and Non-food Products
32 Plugging the anti-fungal gap
Iodopropynylbutyl carbamate (IPBC) is a highly effective fungicide at low usage levels from as little as 15ppm. Annex V: Rinse-off products 0.02%; Leave-on products 0.01%; APDs/DEOs 0.0075% and not to be used in body lotions and body creams or for children under 3 years of age
Dichlorobenzyl alcohol is described as a broad spectrum antifungal preservative with good bacteriostatic properties over a pH-range of 3 – 10 and is permitted in the EU to 0.15%
Dehydroacetic acid and the water soluble sodium dehydroacetate are said to have high antifungal activity Salicylic acid at pH 2 – 4 Caprylhydroxamic acid is said to have antifungal activity Chlorphenesin Undecylenic acid 33 Unlisted preservatives i.e. materials that are not classified as preservatives yet have antimicrobial activity Glyceryl monoesters are a good example and are to be found in many of the alternative systems Glyceryl caprylate; glyceryl laurate; glyceryl undecylenate Sorbitan caprylate Higher diols like pentylene glycol, 1,3-propanediol, methylpropanediol, 1,2-hexanadiol and caprylyl glycol Caprylyl Glycol provides biological synergism with moisturizing and wetting capabilities The one that got it wrong - Aqua/water, phenoxyethanol, methylparaben, sorbic acid, butylparaben, ethylparaben, propylparaben, isobutylparaben, methylchloroisothiazolinone, methylisothiazolinone 34 Essential oils A company in India produces mixtures of naturally occurring essential oils with preservative activity • Mix 1- based on curry leaf and cinnamon leaf oils • Mix 2 - based on orange, lemon grass and sesame oils • Mix 3 - based on basil extract with clove bud, lemon grass and sesame oils • Mix 4 - based on turmeric oil with clove bud, lemon grass and sesame oils All have applications other than for preservative use and have Ecocert approval 35 Biocidal botanical extracts A company in the USA produces multiple component mixtures claimed to have antimicrobial activity • Mix 1: INCI: Origanum vulgare leaf extract, thymus vulgaris (thyme) extract, cinnamomum zeylancum bark extract, olea europaea (olive) leaf extract, rosmarinus officinalis (rosemary) leaf extract, mentha piperita leaf extract, lavandula angustifolia (lavender) flower extract, hydrastis canadensis (golden seal) root extract • Mix 2: INCI: Origanum vulgare leaf extract, thymus vulgaris (thyme) extract, olea europaea (olive) leaf extract, rosmarinus officinalis (rosemary) leaf extract, lavandula angustifolia (lavender) flower extract, hydrastis canadensis (golden seal) root extract • Mix 3: INCI: Origanum vulgare leaf extract, thymus vulgaris (thyme) extract, cinnamomum zeylancum bark extract, rosmarinus officinalis (rosemary) leaf extract, lavandula angustifolia (lavender) flower extract, hydrastis canadensis (golden seal) root extract 36 Natural alternatives p-Anisic acid is found naturally in anise and has a strong action against yeast and mould below pH 5.5 Magnolia officinalis bark extract is not pH dependent and is effective against yeast and mould. Melaleuca alternifolia (Tea tree) leaf oil Rose oil – (phenylethanol) has a mild rose-like odour Usnic aid from tree lichen (Usnea barbata) Honeysuckle (Lonicera japonica) Wasabi (Wasabia japonica) – Japanese Horseradish Asparagopsis armata is a red seaweed gathered off the coast of Brittany that provides natural antimicrobial properties Expert on all things natural is Tony Dweck - www.dweckdata.com37 New? Ethyl Lauroyl Arginate HCl Claimed to be a natural preservative made from lauric acid and L-arginine it is cationic in nature EU approved (V/58) Permitted to 0.4% but not to used for lip, oral and spray products Can be used to 0.8% in soap, anti-dandruff shampoos and non-spray DEOs It is available as 20% active solution and recommended use levels in skin care, hair care and wet wipes 0.5 – 2% Said to be broad spectrum it is water-soluble and stable at pH 3 - 7 38 Chelating agents Chelating agents are not preservatives but may provide a synergistic effect for the overall preservative system. They contribute to the partial solubilising of the cell membrane, which allows preservatives a pathway into the cell. • EDTA and its sodium salts • Citric acid, sodium citrate • Etridonic acid • Pentasodium triphosphate • Natural chelates: Phytic acid, sodium gluconate, gluconolactone, zinc gluconate 39 Thank you for listening John Woodruff www.creative-developments.co.uk 40