Creative Developments (Cosmetics) Limited

Preservatives 1999

 

Preservatives are almost as ubiquitous as water in cosmetic products, in fact few products containing water do not include a preservative and many anhydrous products will also contain them. Earlier this century it would appear that cosmetic preparations contained either ethanol, phenol, resorcinol and salicylates or bacteria and fungi. The antimicrobial properties of the p-hydroxybenzoic esters (parabens) were realised in the mid-twenties and commercial production started in 1929. A textbook on cosmetic preparations published in 1934 [Ref 1] listed a table of preservatives which included parabens, PCMC, PCMX, benzoic acid and sodium benzoate, salicylic acid and formaldehyde. A separate list of antiseptics includes silver salts and also mercuric and arsenic compounds. By 1941 the parabens were the most important group of cosmetic preservatives and de Navarre [Ref 2] described them and their activity in detail.  The second edition (1962) had an extensive chapter on the use of preservatives in cosmetic preparations and included work by the author on the inactivation of preservatives by surfactants and non-ionic emulsifiers. It also described partition coefficients and migration of preservatives, the effect of pH and the use of combinations of preservatives and possible synergistic combinations.

 

Although some materials have been dropped from the early lists and a few additions have been made the parabens continue to dominate. The chart is based on figures given by Steinberg [Ref 3] and shows the frequency of use of the ten most common preservatives in approximately 20,000 formulae registered with the FDA in 1996 and shows the trend in their use since 1987.

 

Preservative

1987

1990

1993

1996

Methylparaben

38.7

38.7

33.7

40.0

Propylparaben

32.0

31.7

27.0

32.8

Imadazolidinyl urea

13.3

12.4

11.6

13.0

Butylparaben

5.7

6.0

8.3

10.4

Ethylparaben

3.1

4.0

6.0

6.5

Phenoxyethanol

1.3

1.9

4.6

6.0

DMDM Hydantoin

1.7

2.7

3.7

5.0

Kathon

2.7

3.5

5.2

4.2

Quaternium 15

3.6

3.5

3.2

3.7

Diazolidinyl urea

0.7

1.4

2.3

3.6

 

 

 

 

 

 

 

 

 

.

 

 

 

The use of methyl and propyl parabens appears to have dipped in 1993 but they had regained their popularity by 1996. The majority of products incorporate more than one preservative and the increase in the use of phenoxyethanol, ethyl and butyl paraben reflects the increased use of a popular propriety mixture. Not shown is the drop in formaldehyde which appeared in 2.6% of products in 1987 and in less than 1% in 1996.

 

From this brief history it is apparent that synergy between preservatives was already being sought by de Navarre in 1941 and has been continued ever since. By achieving synergy the total concentration of the materials may be reduced and the safety in use of the product improved. True biocidal synergism exists when two agents, that are combined, require less of each agent to achieve the same or greater cidal effect than either agent alone [Ref 4]. The majority of preservative suppliers produce mixtures that claim broad spectrum protection and synergistic action. ISP Europe has found that iodopropynyl butylcarbamate (IPBC) acts in synergy with diazolidinyl urea and with DMDM Hydantoin. Published data shows a significant increase in effectiveness when a 100:1 mixture of diazolidinyl urea with IPBC is used compared to either material used alone. A 2000:1 mixture used at between 0.05% - 0.2% is claimed to provide substantially complete protection against six test organisms when subjected to a 28 day challenge test. The organisms were Aspergillus niger (AN), Candida albicans (CAN), Esterichia coli (ECOLI), Pseudomonas cepecia (PC), Pseudomonas aeriginosa (PSA) and Staphylococcus aureus (SA). .

 

The potential for synergy of preservatives with IPBC has been investigated by other workers; Gruening [Ref 5] describes its efficacy in combination with the majority of popular preservatives for cosmetic products and claims that any preservative with a minimum inhibitory concentration (MIC) of less than 1000 ppm against either PA or CA is a suitable candidate for blending with IPBC. In particular 5-bromo-5-nitro-1,3-dioxane and 2-bromo-2-nitropropane-1,3-diol, methyl(chloro)isothiazolones, chlorhexidine and various quaternaries have their activity enhanced when combined with IPBC. Koch and Milker [Ref 6] claim that IPBC is not only synergistically effective against contaminating organisms in suitable blends, its safety profile also reduces the potential of the other preservative(s) in the blend for causing allergies or contact dermatitis. ISP provide a suitable blend of IPBC with diazolidinyl urea as Germall Plus; Jan Dekker blend IPBC with DMDM hydantoin as Dekaben DMM and Lonza Inc. supplies a similar mixture as Glydant Plus which, according to Steinberg, is currently the preservative showing the fastest growth in popularity in the USA.

 

Although a long way from the top ten in the chart the use of methyldibromo glutaronitrile is increasing. Shulke and Mayr supply it as a 10% solution in dipropylene glycol and in various combinations with other preservatives including methyl(chloro)isothiazolones,  2-bromo-2-nitropropane-1,3-diol and phenoxyethanol. It is also supplied by the Calgon Corporation as Merguard 1190 in solution in dipropylene glycol and with phenoxyethanol as Merguard 1200. Nipa Laboratories have included it in Nipaguard TBK in association with 2-bromo-2-nitropropane-1,3-diol, mixed parabens and phenoxyethanol. Data published by Nipa shows that when tested according to the protocol given in the British Pharmacopoeia (1993) it is effective at from 100 - 1000ppm depending on the base product. Because of the 2-bromo-2-nitropropane-1,3-diol content Nipa undertook a study of the nitrosamine-forming potential of Nipagard TBK. A simple triethanolamine-stearate lotion was prepared with a control having sodium hydroxide substituted for the triethanolamine. Both contained Nipaguard TBK at 0.03%, 0.06% and 0.10%. No nitrosamine compounds were detected in any of the samples after storage at ambient temperature for 6 months and at 40oC for 3 months.

 

Silver salts were on the list of antiseptics in Chilson’s book published in 1934 [Ref 1]; a silver chloride titanium dioxide composite is the basis of the JMAC range of antimicrobial products produced by Johnson Matthey in association with Microbial Systems International. Extensive literature is available from the latter company which describes its activity and applications, its toxicity and the current status of registration throughout the world. It is approved for use in the EU subject to certain restrictions regarding use in oral, eye and baby products. Approval for use in cosmetics in the USA is expected shortly and an application for use in Japan is underway but is probably some years from final approval.

JMACTM is a silver chloride/titanium dioxide composite and JM ActiCareTM is a suspension of particles of a silver chloride/titanium dioxide composite in a water/sulfosuccinate gel which improves its activity against yeasts and moulds. Although recommended for most types of leave-on and rinse-off products JM ActiCare is specially useful for preserving products containing finely dispersed particulates such as sun screen preparations based on microfine inorganic oxides and makeup preparations. Recommended useage levels are from 0.01 - 0.05% depending on the product category, the insoluble particles of silver chloride/titanium dioxide composite represent no more than 10% of this and the particles are less than 5 microns in size so no visual presence should be noticed. When incorporating JM ActiCare into the formulation it is important not to add it to the oil phase as its activity is seriously affected if the particles become coated with oil. It is stable across the pH range 3 - 10 but it is affected by xanthan gum which binds the silver, and by some AHAs but not lactic and glycolic acids. Materials such as ascorbic acid and sodium metabislfite which may reduce the silver chloride need careful evaluation and strong cationic materials may also be detrimental.

 

The positive list of permitted preservatives in the EU makes it almost impossible for new ones to be introduced but various materials are recommended for cosmetic use which improve the preservative efficacy of the product. Well known are chelating agents, propylene glycol and some antioxidants. The antimicrobial activity of cationic surfactants is known and utilised but it may be overlooked that some amphoterics are also active. Dr. Straetmans supplies a number of glyceryl esters under the Dermosoft trade name which have antimicrobial activity against Gram +ve organisms when used at 2% or above. When used as additives for skin care products for their moisturising and skin feel properties they may make it possible to significantly reduce the normal preservative content. Inolex supplies glyceryl caprylate, capryl glycol, phenylpropanol, sodium levulinate and anisic acid, either as individual materials or in mixtures, as its range of Lexgard Bio-active excipients. Whilst recommended for their multifunctional attributes as moisturisers, co-emulsifers and wetting agents they coincidentally have an effect against bacteria, moulds and yeast. Glyceryl caprate and glyceryl caprylate may be found in propriety brands of deodorants which are otherwise free of conventional bactericides.

 

Despite de Navarre’s work and all that has been written since, product contamination still occurs because the preservative system has not been properly designed for the product and its packaging. Preservatives may migrate into the oil phase or be absorbed by the packaging, they may be added  to the product at too high a temperature or be used at the wrong pH. They may be inactivated by other ingredients or be overloaded by massive contamination. Preservatives should not be regarded as a substitute for good manufacturing practices. Much has been written in recent years about hazard control at critical control points (HACCP) and many customers are now insisting that their suppliers formally adopt this procedure. More than 90% of all microbial problems are caused by contaminated production water [Ref 7] and in storage vessels and pipework biofilms can readily be formed which become permanent contamination carriers. These films are resistant to chlorine and most commonly used disinfectants and all pipework must be regarded with suspicion.

 

 

 Ref 1     Chilson, Francis; Modern Cosmetics, The Drug and Cosmetic Industry, New York, 1934

 

Ref 2      de Navarre, Maison; The Chemistry and Manufacture of Cosmetics, D van Nostrand Co. Inc. new York 1941

 

Ref 3               Steinberg, David; Frequency of use of preservatives in the United States, paper given at Preservatech, Paris, France 1996

 

Ref 4               Simpson, D L; Synergism in cosmetic preservation, ibid

 

Ref 5               Druening, Rainer, IPBC Preservative combination systems for material protection, ibid

 

Ref 6      Koch, C.S., Milker, R; As much as necessary, as little as possible, paper given at Preservatech, Paris, France 1998

 

Ref 7      Diehl, KH, Important secondary conditions for optimal use of cosmetic preservatives, paper given at In-Cosmetics, Birmingham, UK 1990