Preservation and Product Protection:The Next Step Forward

Steven F. SchnittgerEstee Lauder CompaniesOctober  20th, 2015

Today’s Presentation The need for Preservatives and Product

Protection Review the status on conventional

preservatives around the globe The use of multi-functionals and

potentiators in cosmetic formulation today Physiochemical factors which effect

preservation Packaging as a form of product protection

Mission Statement Every cosmetic manufacturer has a dual

responsibility relative to the quality of their products: Ensure that the product, as purchased, is free from

the number and types of microorganisms that could affect product quality and consumer health

Ensure that microorganisms introduced during normal product use will not adversely affect the quality and safety of the product.

Adherence to Two Programs

To achieve these goals, two programs have to be in place (and you cannot do one without the other): Proper Preservation and Protection of the

Marketed Product Adherence to cosmetic good manufacturing

practices and Quality Assurance – which includes an effective “Environmental Monitoring Program”

Preservation and Product Protection To ensure stability, efficacy and quality of a

cosmetic product:

All aqueous based products need to be preserved or have some form of product protection to minimize the risk of microbial contamination and ensure product quality and stability.

Growth of Micro-organisms

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Why we need Preservatives!

With a Preservative Without a Preservative

Product Protection: A Multi-faceted Approach

Protection can be delivered solely based on chemicals whose only function is preservation.

Protection can also be delivered through multifunctional ingredients whose primary attributes may be some function other than preservation, but does contribute to the preservative efficacy of the formula

Product Protection Product protection can also come from

physiochemical properties such as pH, reduced water activity, or mfg. / fill temperatures which creates an environment which is recognized as low risk to microbial growth (ISO 29621)

These properties play a minor role in aqueous based products, but may play a major role in protecting anhydrous products.

Product Protection The final method of protection is through the use

of packaging which could help minimize the ability of the consumer or the environment to contaminate the product.

The combination of packaging and risk assessment help to determine product risk and testing requirements.

The combined parameters of Challenge Testing, Risk Assessment, and Packaging are outlined in ISO 11930.

Production Protection

Preservatives

Multi-functionals

Potentiators

Physiochemical Factors

PackagingPackaging

Preservation “Preservation is the process by which a chemical or

physical agent prevents a biological deterioration of materials” *

According to EC Regulation (EC) 1223 /2009 on cosmetic products:

“A preservative is a substance which is exclusively used or mainly intended to inhibit the development of microorganisms in a cosmetic product and are listed in Annex V. “

* Block, Disinfection, Sterilization, and Preservation, 4th Edition, 1991

Preservative Type 2007 2010 2013

Methylparaben Paraben 11609 13434 13423

Propylparaben Paraben 9329 10421 10423

Phenoxeyethanol Glycol ether 5123 8878 11641

Butylparaben Paraben 2784 5289 5114

Ethylparaben Paraben 3789 4869 5004

Methylisothiazolone Isothizolone 1409 2408 3391

MI / CMI (Kathon CG) Isothizolone 1392 2235 2774

DMDM Hydantoin F.R 1665 2035 2252

Imidazolidinyl urea F.R 2266 2007 1822

Benzyl alcohol ** Alcohol 1125 1991 3042

Diazolidinyl urea F.R 1299 1644 1662

Chlorphenesin Halogenated 441 1065 1657

Sorbic acid / K sorbate Organic acid 1259 1037/1456 1326/ 2697

Dehydroacetic acid / Na Organic acid 866 948 1954

Iodo-propynyl butyl-carbamate (IPBC)

Halogenated 429 834 972

Na Benzoate Organic acid 1153 1334 2119

Quaternium -15 F.R 531 389 252

Preservative List

Except for Benzyl alcohol every one of these molecules only has one function – Preservation!

Except for the Organic acids everyone of these compounds is under some type of regulatory, environmental, or safety review.

Because of the restrictions on the parabens, MI /CMI, the use of Phenoxeyethanol has significantly increased.

Only the Organic acids, Phenoxeyethanol, and Benzyl Alcohol has shown significant increases in usage

* Thank you Dave Steinberg for keeping this list up to date

Multifunctional Ingredients

Industry has moved to using ingredients Multi-functional Ingredients to help potentiate the preservative efficacy of their formulations.

When used in combination with conventional systems data shows that products preserved with these chemistries have shown to help improve preservative efficacy.

Case Study: Optimal Eye Cream

Water, squalane, glycerin, dimer dilinoleyl dimer dilinoleate, stearic acid, glyceryl stearate, beeswax, polysorbate 60,

phytosteryl/isostearyl/cetyl/stearyl/behenyl dimer dilinoleate, pentylene glycol, peg-10 stearate, behenyl alcohol,

octyldodecyl pCA, butylene glycol, dipalmitoyl hydroxyproline, glyceryl stearate Se, tocopheryl acetate, dimethicone, arginine,

trehalose, hesperidin methyl chalcone, hydroxyethylacrylate/sodium acryloyldimethyl taurate copolymer,

pimpinella anisum (anise) fruit extract, dipeptide-2, palmitoyltetrapeptide-7, yeast extract, iris florentina root extract,

artemia extract, hericium erinaceum extract, camellia sinensisleaf extract, kjellmaniella gyrata extract, caprylyl glycol,

steareth-20, ethylhexylglycerin, aminoethanesulfinic acid, etidronic acid.

7th Amendment In 1976 legislation 76/768/EEC was enacted in the

EU to ensure product safety. The 7th Amendment required the results of a recognized challenge test to be included in a product information package for all products marketed within the EU.

Multifunctional Ingredients A second reason for the use of multifunctional

ingredients is the potential reduction in risk of sensitization due to the over use of conventional systems.

The combination of a multifunctional with a conventional preservative system can lower the risk of sensitization and at the same time increase preservative efficacy versus when used alone.

Multifunctional Ingredients Many cosmetic ingredients have been recognized for

years for their multifunctional properties such as Alcohols, Essential oils, EDTA, and Surfactants but today many of these ingredients are now becoming main stream in the area of preservation.

Today I will briefly discuss 2 of those ingredients: Caprylyl glycol Ethylhexylglycerin

Glycols Multifunctional, Potentiator, Humectant

Propylene, Butylene Glycol (3.0 – 6.0%) improves solubility reduces oil/water partitioning improves stability Used as a Preservative Potentiator

1,2 Hexanediol, Pentylene Glycol (1. 0 - 2.0%) Used an Multifunctional with Antimicrobial Properties Moisturizer Formulation stabilizer

Caprylyl Glycol (0.5 - 1.0%) Used an Multifunctional with Antimicrobial Properties Improves skin hydration

Capryly Glycol 1,2 Octanediol Soluble in both water and cosmetic esters Has antimicrobial, moisturizing and humectancy

activities Can also be used as solubilizer or delivery system Shown to have synergy with many conventional

preservative systems Has broad spectrum activity at all pH ranges Limited fungal activity Used in combination with organic acids and other

conventional systems

Caprylyl Glycol Synergistic activity comes from its ability to

help in penetration through the cell wall. Anti-microbial activity comes from its ability to

disrupt the cell membrane Main benefit is that it stays at the water / oil

interface where preservation is needed the most.

Caprylyl Glycol Used in combination with many other

preservatives to help in activity: Phenoxeyethanol Kathon CG Sorbic Acid IPBC Chloroxylenol

CAPRYLYL GLYCOLSynergy with Phenoxeyethanol

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Caprylyl glycol works well with many preservatives/boosters to provide quicker kill

Phenoxeyethanol

Symrise

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Diol inemulsion

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Diol inWater

Efficacy of Caprylyl Glycol;Effect on Order of Addition

EthylhexylglycerinMultifunctional ingredient:Active component in deodorantsHas both emollient and humectant propertiesShows strong synergy with other preservatives such as parabens, Phenoxeyethanol, and Isothizolone.

___0.1 % Ethylhexylglycerin

___

0.9 % Phenoxyethanol

___ 0.1 % Ethylhexylglycerin / 0.9 % Phenoxyethanol

Shulke Inc.

EthylhexylglycerinImproved Efficacy of Phenoxyethanol

___0.1 % Ethylhexylglycerin

___

0.9 % Phenoxyethanol

___ 0.1 % Ethylhexylglycerin / 0.9 % Phenoxyethanol

EthylhexylglycerinImproved Efficacy of Phenoxyethanol

Shulke Inc.

New Preservative Systems Need to build the formulation around the

preservative system Preservative may not be compatible with

emulsion type Risk of sensitization may be higher Cost per kilo may be higherWill require more work by the chemist!

Recap In conclusion the use of multifunctional

ingredients can help in reducing the amount of a conventional preservative in a formulation and

still guarantee efficacy and safety.

Preservative Potentiators

Potentiation can be defined as: “The enhancement of an antimicrobial agent through the

addition of a microbiologically inactive or weakly active component that presumably increases the susceptibility of the microbial target to preservative action.” *

On their own they would not supply stand alone activity

*Russell, Disinfection, Preservation, and Sterilization, 2nd edition, 1992

Preservative Potentiators Examples to be discussed: EDTA Butylene Glycol 1,3 Propanediol (Zemea)

EDTA(Ethylenediamine Tetraacetic Acid) A chelator which works by binding trace metals

is which is needed for the survival of the organism Has activity against gram negative bacteria Also reported activity against fungus Helps to prevent against antimicrobial resistance

Helps in preventing discoloration, fragrance oxidation, cloudiness from metal ion impurities and product rancidity Works well in an acid pH range Na2EDTA>Na3>Na4

Butylene Glycol Used to help stabilize emulsions Potentiates the activity of parabens and

Phenoxeyethanol Helps solubilize and maintain preservatives in the

water phase of an emulsion Has bacteriostatic activity versus bactericidal

activity Retards the loss of fragrances

1,3 - Propanediol 1,3-Propanediol is a skin-friendly, corn derived

natural glycol with enhanced performance benefits. Has humectant, solvent, emulsifier, and preservative booster, due its anti-fungal / anti-microbial testing CTFA Challenge Test data showed that Propanediol

has antimicrobial properties that prohibit contamination during shipping and handling.

In the CTFA Challenge Test, 1,3 PDO had similar performance to PG and BG in reduction of bacteria, yeast and mold.

A skin hydration test was conducted on 10 female volunteers aged from 46 to 65. The 5 test creams were applied on the forearms of the volunteers who had dry skin on that area. The control cream replaced the glycol with water to evaluate the relative hydration properties of the other ingredients. A Corneometer 825 PC® (Courage & Khazaka) was used to measure skin hydration immediately after each application during the test.

Skin Hydration Study

DuPont

DuPont

Recap

In conclusion the use of ingredients considered as a Preservative Potentiator or Booster can help

in reducing the amount of a conventional preservative in a formulation and improve overall

product safety scores.

Physio - Chemical Factors: Impact on Preservative Effectiveness

pH of emulsion (water phase)

Temperature of Preservative Incorporation

Temperature of Manufacturing and Filling Temperature

Water Activity

Order of addition of your preservative system

Percentage of Active Ingredients in Formula

Type of Surfactant System

• According to ISO 29621 a Low Risk Product:

“Is a product that whose composition denies microorganisms the physical and chemical requirements for growth or survival”

This hostile environment is created by:o High alcohol content o Extreme pH conditionso High glycol, glycerin, polyol levelso Deodorants and antiperspirants with high aluminum

chlorohydrin levelso Anhydrous products manufactured and filled at high

temperatures o Low water activity

Low Risk Products

Packaging can be the 1st Line of Defense.

Prevent entry of bacteria, moisture, air, and product buildup

Applies to both storage and finished product.

Use sanitary or sterile procedures when possible!

Comply with all cGMP standards

Packaging A Major Role in Preservation

Final Packaging Low Potential Risk - Pumps, Sprays,

ophthalmic tip tubes, tubes with one way valves.

Moderate Potential Risk – Tubes, bottles, flow through pens.

High Potential Risk – Wide orifice jars, sponge applicators

Conclusion Product Protection is a multi-faceted approach to

ensure long term quality and stability of a cosmetic product

There has been a serious reduction in the number of acceptable preservatives that can be used globally which has lead to the increased use of multifunctional ingredients to ensure preservative efficacy.

Protective Packaging can play a major role in the overall scheme for product protection.