Preservation of Personal Care Products

1 10/20/2011. Preservation of Personal care Products A Microbiologist's View PCPC Microbiological Workshop October 26, 2011. Deidre L. Mitchell Development Manager Microbiology Unilever Trumbull, CT. Presentation Objectives Purpose of a preservative Impact of pH, temperature and water activity on preservative requirements for a product formulation Impact of formulation ingredients on preservatives Preservative Challenge Testing Other considerations impacting preservative selection (Regulatory and Public Relations (PR). Consumer Use Distribution 1. 10/20/2011. Purpose of a Preservative Preservatives are essential ingredients added to a product to prevent and/or minimize the growth of microorganisms. Preservatives are added to Products to protect the quality and consumer safety for the intended shelf life of a product . Note: Preservatives should be used with consideration for the intended consumer. Preservatives have long been recognized as skin Ultimately, Preservatives are essential to protect the quality of the product and safety of the consumer.)

2 1 Meyandier, JM. Meyandier J, Colmas A et al. Allergie aux conservateurs. Ann Dermatol Venerol 1982;. 109:1017-23. Key Points on Preservatives Preservatives will reduce any incidental contamination. Preservatives are not intended to compensate for poor manufacturing practices. It must be recognized that despite adequate product Preservation and the following of cGMP's, Personal care Products are NOT immune to microbiological exposure. Success is a combination of robust Preservation in combination with good manufacturing processes. 2. 10/20/2011. The Ideal Preservative Globally acceptable No negative public relation issues (PR). Wide pH compatibility Broad spectrum activity (bacteria, yeast, mold). Cost effective Safe and non-irritating at minimal use levels Easy to incorporate into product formulations Synergy with co-preservatives to reduce concentration of preservatives needed Preservative Mechanisms of Action Preservatives are not selective like antibiotics, they attack many sites on the cell membrane.

3 Ref. Principles and Practice of Disinfection, Preservation and Sterilization, Third Edition, Blackwell Science LTD, London, UK, 1999, 3. 10/20/2011. Factors Affecting Microbial Growth Bacterial growth & survival are affected by: Physical Conditions pH. Temperature Water activity (aw). Nutrition Environment Presence/absence of antimicrobials or preservatives Importance of pH. pH Influence Molds prefer acidic pH. Bacteria prefer neutral/alkaline pH. Note: Some Gram negative organisms can tolerate an acidic pH ( cepacia can grow at pH 3). Extremes of pH can be self-preserving ( pH < or greater than ). 4. 10/20/2011. pH Personal care Products Hair Gels Facial Cleansers 1 2 3 4 5 6 7 8 9 10 11 12 13 14. Shampoo Skin Cream Body Wash Hair Conditioner No Chemical Preservative Required Chemical Preservative Required Water Activity and Preservation What is It? Water available for microbial growth . Not the percentage of water in a formulation The higher the aW the greater the potential risk of microbial contamination Water activity measurements can be used to provide direction as to how to best preserve a product 5.

4 10/20/2011. Water Activity (aw) and Potential for Growth Water Activity pH Level Problem product Organism Examples 5-9 Gram Positives and Shampoos and Gram Negatives Emulsions 5-9 Gram Positives and Eye area Products Gram Negatives, Pseudomonads Limited < Gram Positives and Hair Conditioners Gram Negatives, Pseudomonads Limited 5-9 Mold and Yeast Some Talcs 5-9 Osmotolerant Yeast Some Anti- Perspirants 5-9 Osmotolerant Molds Below 5-9 None Ref. Daniel K. Brannan, Cosmetic Microbiology, A Practical Approach, Second Edition , Taylor and Francis, New York London, 2006, page 50. Application of Water Activity Values Water Activity (aw)< Typical product Type Preservative Requirement Based on Water Activity Only Shampoos Anti-bacterial3 and Anti-fungal4. Foam/Bath/Shower Products preservative required Hair Conditioners Creams and Lotions Oil-in-Water Emulsions Water in Silicone Emulsions Unlikely to require an anti- Concentrated Liquids bacterial preservative, may (Typically > 40% active) require an anti-fungal preservative < High alcoholic deodorants Preservative not required 3 Aw - Inconsistency in literature for Gram Negative bacteria.

5 4 Many preservatives have antibacterial and some antifungal activity ( Isothiazolinones/Formaldehyde) It does not imply that an antifungal agent ( Parabens/Glycacil) is always required. 6. 10/20/2011. Temperature Thermophiles Mesophiles Psychrophiles Body temperature- most human pathogens grow best at 37oC. -10 0 10 20 30 40 50 60 70 80 90 100 C. Yeasts Molds Other Ingredients Impacting Preservation Positive Ingredients Alcohol ( Ethanol > 20% level required to be self-preserving). Chelating agents Disodium EDTA. Active Ingredients - ( Salicylic Acid, Triclosan, Zinc Pyrithione). Potentially Negative Ingredients Quality of Raw Materials Increased demand on Preservative Growth Promoting - Natural Extracts/Glucose Certain ingredients can inactivate preservatives, such as, sunscreens, anionics, and starch. 7. 10/20/2011. Importance of Chelating Agents EDTA can improve the performance of some preservatives against microorganisms.

6 Believed to weaken cell envelope by removing magnesium ions May permit preservative to enter cell more easily and attack cellular target Chelating agents can improve efficacy of preservatives against Gram negative organisms such as and Recommend incorporating a chelating agent into product formulation to strengthen the preservative system. How EDTA Enhances Preservative Activity Preservative Preservative calcium and magnesium ions stabilize the outer and inner membranes of Gram negative cells - this helps protect them from preservatives LPS of outer membrane Inner membrane Add EDTA chelates calcium and magnesium which destabilizes Add EDTA the cell membranes EDTA. - helping preservatives to attack the cell Loss of Ca/Mg increases repulsion between Normally LPS excludes preservatives but negatively charged phospholipids - making it easier up to 40% of LPS molecules lost following for preservatives to enter the cell EDTA treatment EDTA WILL NOT WORK IN FORMULATIONS WITH HIGH LEVELS OF Ca or Mg 8.

7 10/20/2011. Preservative Selection Additional Considerations Legal Restrictions Company Restrictions PR Restrictions Preservative Selection Legal Microbiologists need to be aware of the restrictions on preservatives When providing recommendations to Chemists/Formulators! Approvals Documentation European Union (EU) Pre-approves preservatives and publishes a positive list known as Annex VI. China Hygienic Standard for Cosmetics (version 2007/01) issued by China Ministry of Health (MOH). Canada Publishes a hotlist of ingredients that are either prohibited or restricted Japan Publishes a positive list (restrictive and classifies approvals based on the end use of the cosmetic United States FDA has a list of prohibited or severely restricted ingredients 9. 10/20/2011. Preservative Selection - Legislation May require additional testing ( Shelf life justification). Europe: Period After Opening (PAO) Requires that all cosmetics with a shelf life of < 30 months must have a best used by date on the label.)

8 US (FDA Regulations) All cosmetics need not be sterile but they must not contain microorganisms that are pathogenic and the density of non-pathogenic must be low in the product formulation and remain at low levels for the anticipated product shelf life. Products must be tested for microbiological quality before being released to the trade. Products must be tested for preservative efficacy during the product development process. Preservative Selection Public Relations (PR). Every preservative is fighting some degree of public scrutiny! All preservatives have a restriction/issue somewhere in the world! Based on level (dose) restrictions, product type (rinse off, leave on, baby categories, mucous membrane), even differences within a chemical family (isothiazolinones, parabens). Microbiologists should consult with Regulatory to be aware of the latest views on the preservatives they are recommending to Formulators.

9 The legal and regulatory landscape is constantly changing so be aware . 10. 10/20/2011. Preservative Selection Compatibilities pH. and Temperature of Addition Preservative pH Temperature Parabens 3-8 Add at emulsification temperature (75-80 C) to water phase Benzoic Acid < Typically added to water phase and added early to facilitate mixing DMDM Hydantoin 3-9 Stable up to temperatures of 80 C. *At temperatures exceeding 80 C, preservative will break down and release formaldehyde MCI/MI < Add in cool down phase < 50 C. Phenoxyethanol 3-10 Often added with Fragrance, MCI/MI Methylchloroisothiazolinone and Methylisothiazolinone Stable up to 85 C. Ref. David Steinberg, Preservatives for Cosmetics, Second Edition, Allured Publishing, 2006. Ingredients that have an Impact on Preservation Preservative Absorbers Kaolin Silica Talc Titanium Dioxide Preservative In-activators Cellulose gum Alkaline pH. Lecithin Over-heating Non-ionics Polysorbates Xanthan gum 11.

10 10/20/2011. Preservative Neutralizers and In-activators Parabens Lecithin, Non-ionic surfactants, polysorbate, gums, alkaline pH, polyethylene glycol Alcohols Gums, non-ionic surfactants, especially Tweens MCI/MI. Bisulfites, secondary amines, strong nucleophiles ZPT is not compatible with MCI/MI. Preservative Neutralizers and In-activators Phenolic and Chlorophenolic Compounds Polysorbate 80, Non-ionic surfactants, proteins Carboxymethylcellulose, polyethylene glycols, lecithin Organic Acids Neutral -> Alkaline pH, non-ionic surfactants, CaCl2, Tweens Formaldehyde Donors Incompatible with Parsol 1789. 12. 10/20/2011. Preservative Selection - Stability Temperature Is it stable for life time of product ? Take account of countries it will be used in Is it stable for distribution? Take account of distribution, especially if global or into hot tropical regions UV Stability Does preservative need to be UV stable Transparent Packaging Preservative Selection - Partitioning The preservative must be active in the aqueous phase of a formulation to be microbiologically effective and functional.