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John Woodruff: the personal stuff
2
1960: joined Smith & Nephew Research1976: 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 manufactureTwo 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 Chemist1996 – Present: Regular contributions to Soap, Perfumery and Cosmetics (SPC)Supports the Distance Leaning Course run by the SCSLectures on product formulation at the Principles and Practice of Cosmetic Science When he is not working he is sailing.
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 stuffEU 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
15
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
Annex V Simplified. 54 ingredients plus salts
Useful permitted preservatives
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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 sorbatesUndecylenic acid + salts
Annex V Very Simplified. 26 ingredients plus salts
Useful permitted preservatives
17
Benzoic acid & Na benzoate (0.5% in Leave-on)
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-CresolChlorphenesin (0.3%) Phenoxyethanol (1.0%)
Dehydroacetic acid, Na dehydroacetate (0.6%)
Phenoxyisopropanol [Rinse-off only]
Diazolidine urea Polyaminopropyl biguanideDichlorobenzyl Alcohol (0.15%) Quaternium-15
DMDM Hydantoin Silver chlorideGlutaral Sodium Hydroxymethylglycinate
Imidazolidinyl ureaSorbic acid and sorbates (0.6% as acid)Undecylenic acid & salts (0.2% as acid)
Annex V Very Very Simplified
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
19
Frequency of Use: List prepared by David Steinberg showing numbers of products containing preservatives as shown
US 2007 US 2010 Canada
2008
Canada
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
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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%
Frequency of Use: List prepared by David Steinberg showing numbers of products containing preservatives as shown US 2007 US 2010
Can
2008
Cana
2010
Simplified by preservative types
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0.00%
2.00%
4.00%
6.00%
8.00%
10.00%
12.00%
14.00%
16.00%
1 2
Trends in preservative use: USA 2007 - 2010
Phenoxyethanol
Formaldehyde donors
MCI + MI + MCI
Benzyl alcohol
Caprylyl glycol
Trends in preservative use in EU
European skin care
2009 2010 2011 2012 2013 2014
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
23
0.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00%
1 2 3 4 5 6
Trends in European preservative use
Benzoates Isothiazolines Phenoxyethanol
Phenoxyethanol
Benzoic acid/Benzoates
Isothiazolines
Parabens make up the difference @ ~ 61%
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
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Use organic acids
• .
30
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
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
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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 <pH7
Salicylic acid at pH 2 – 4
Caprylhydroxamic acid is said to have antifungal activity
Chlorphenesin
Undecylenic acid
33
Unlisted preservativesi.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, cinnamomumzeylancum 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