Product Stability

or How to make sure your product stays as good as new

John Woodruff
Creative Developments (Cosmetics) Ltd
www.creative-developments.co.uk

Product Stability
What is it? How do we test it? How can we improve it?
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Product Stability
What is it? How do we test it? How can we improve it?
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Definition of Stability

In mathematics, stability theory addresses the stability of solutions of differential equations and of trajectories of dynamical systems under small perturbations of initial conditions. In probability theory, the stability of a random variable is the property that a linear combination of two independent copies of the variable has the same distribution, up to location and scale parameters. ...
John Woodruff; Creative Developments (Cosmetics) Ltd.

Definition of Stability

- the quality of being enduring and free from change or variation - resistant to change of position or condition - firm and dependable; subject to little fluctuation - not taking part readily in chemical change
John Woodruff; Creative Developments (Cosmetics) Ltd.

Definition of Stability

What do we understand about it with regard to cosmetic products? That a product remain fit for purpose

Appearance Purity including lack of microbial contamination Efficacy

That it remains fit for purpose for a period of not less than 36 months from manufacture and not less than its PAO declaration
John Woodruff; Creative Developments (Cosmetics) Ltd.

Examples of Instability

Examples of Instability
Obvious

Emulsion breakdown Perfume changes Colour changes Viscosity changes Fungal growth Wax crystallisation Sediment in clear lotions
John Woodruff; Creative Developments (Cosmetics) Ltd.

Examples of Instability
Less Obvious

pH changes Loss of activity

Vitamins Antioxidants Enzymes Preservatives

Photo-degradation of UV filters Microbial growth

John Woodruff; Creative Developments (Cosmetics) Ltd.

Emulsion Creaming

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Emulsion Breakdown

4 days at room temperature

1 month at room temperature

1 month at 45C

1 month at 45C
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4 days at room temperature

1 month at room temperature

John Woodruff; Creative Developments (Cosmetics) Ltd.

Viscosity Changes
Increasing 70 60 50 40 30 20 10 0 Initial 5 days 10 15 20 25 30 days Decreasing Stable

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Worst Nightmare!

Atmospheric Mould Colonies

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Crystal Growth

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Product Stability
What is it? How do we test it? How can we improve it?
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Testing for Stability

Prepare a pilot batch and store it in its retail packaging and check that it remains fit for purpose for a period of not less than 36 months from manufacture and not less than its PAO declaration! Impractical What other options?

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Testing Schedules

Examples of suitable schedules are given in the IFSCC Monograph Boots publishes a scheme that its suppliers are expected to use - GR10 Distance Learning Course (DLC) includes suggestions in its module on stability

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Testing Schedules
IFSCC Monograph

40 ambient humidity 200 / 250 ambient humidity 370 ambient humidity 450 ambient humidity 370 & 80% relative humidity Freeze / Thaw Light exposure

retain as control 60 months 6 months 3 months 1 month

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Testing Schedules
DLC Recommendations

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John Woodruff; Creative Developments (Cosmetics) Ltd.

DLC Recommendations
1 month assessment (all storage conditions) 2 month assessment (all storage conditions) 3 month assessment (all storage conditions) 6 month assessment (all storage conditions) 9 month assessment (all storage conditions) 1 year assessment (all storage conditions) 18 month assessment (5C and RT storage conditions only) 2 year assessment (5C and RT storage conditions only) 30 month assessment (5C and RT only) 3 year assessment (5C and RT storage conditions only).

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Testing Schedules
Boots recommendation - Stability and final pack compatibility of all cosmetic and toiletry products should be assessed to establish that they are stable and that no separation, crystallisation, contamination, degradation or other instability occurs within the claimed product shelf life
Stability Requirements Must be safe to use, effective and stable in final pack for at least 36 months at: 0C to 23C Must be safe to use, effective and stable in final pack for at least 3 months at: 30C

Products sold in temperate climates Products sold in tropical climates

0C to 30C

40C

Product must also be safe to use within their specified Period After Opening (PAO), no matter at what point in their shelf life they are first opened.
21 John Woodruff; Creative Developments (Cosmetics) Ltd.

What should be checked?

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John Woodruff; Creative Developments (Cosmetics) Ltd.

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John Woodruff; Creative Developments (Cosmetics) Ltd.

What is Important

Consider the function of the product under test and decide whether or not the changes observed could affect this Consider the safety of the product under test and decide whether or not the changes observed could affect this Consider whether the changes observed affect the aesthetics of the product under test Note under what storage conditions any changes observed take place and try to relate these to the environment in which the product is to be sold Look for significant trends in changes of product attributes
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Talking Points

What is important for this product in this packaging for this market? Setting product specification

Minimum and maximum for each parameter

Why these numbers? Have products been prepared and tested at extreme specification limits? Release specifications / shelf-life specifications What matters?

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Accelerated Testing for Stability

Prepare a pilot batch and store it in its retail packaging:

Room Temperature (RT) for 24 months 4C for 3 months 40C for 3 months 4C/40C Cycle for a number of cycles In a N-facing window or a light box for 3m

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Testing for Stability

Monitor for changes in appearance (Subjective measurements)
Homogeneity Colour Glass

slides Microscope Texture and skin feel Odour

27 John Woodruff; Creative Developments (Cosmetics) Ltd.

Testing for Stability

Monitor emulsion stability

(Physical changes)

Emulsion breakdown

Creaming or settling

Glass slides aeration and density/opacity Microscope droplet size changes; crystals

Viscosity changes Rheological changes Centrifuge tests Turbiscan Lumifuge

John Woodruff; Creative Developments (Cosmetics) Ltd.

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Emulsion Creaming

3 months at 40C

18 months at RT

What ways are available for quicker results

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Microscope Examination

4 days at room temperature

1 month at room temperature

1 month at 45C

4 days at room temperature

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1 month at room temperature

1 month at 45C
John Woodruff; Creative Developments (Cosmetics) Ltd.

Viscosity Changes
These are actual viscosity graphs of 5 different w/o emulsions differing only in emulsifier used

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Rheological Changes

For suspensions measure yield values

Yield value is the minimum force necessary to induce flow Measured using a rheometer or a Brookfield Digital Viscometer with small sample adaptor Yield values may be used to determine the suspending power of a composition; very useful when developing scrubs
http://www.connock.co.uk/articles_exfoliants.htm
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Accelerated Stability Testing

Centrifuge

5 minutes or more at 5,000 rpm A centrifuge designed to run at very high speeds and thus generate very high centrifugal force is called an ultracentrifuge. Suspensions which would settle only very slowly or not at all under gravity can be made to separate quickly in such a device!

Ultracentrifuge

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John Woodruff; Creative Developments (Cosmetics) Ltd.

The LUMiFuge
Demixing phenomena, like sedimentation, flotation or consolidation are directly measured by the LUMiReader, LUMiFuge or LUMiSizer due to the patented cutting-edge STEP-Technology. This permits to obtain Space- and Time-resolved Extinction Profiles over the entire sample length of up to 12 different samples simultaneously. Parallel light (I0) illuminates the entire sample cell and the transmitted light I is detected by thousands of sensors arranged linearly across your whole sample from top to bottom with a microscale resolution. Transmission is converted into extinction by lg I/I0 and particle concentration may be calculated.
www.lum-gmbh.com/pages/.../lumifuge/products_lumifuge.htm

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John Woodruff; Creative Developments (Cosmetics) Ltd.

The LumiFuge

The multisample analytical centrifuge LUMiFuge accelerates the demixing process up to 2300 times compared to traditional test tube tests. Stability tests and shelf-life determinations of original dispersions are up to 2500 times faster than performed in a test tube under earth gravity.
John Woodruff; Creative Developments (Cosmetics) Ltd.

http://www.lum-gmbh.com/pages/products/lumifuge/products_lumifuge.htm
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Turbiscan
The Turbiscan measures transmitted and reflected light passing through a sample and graphs the results. Differences over time are due to changes in droplet size and distribution

www.formulaction.com/stab_lab_gb.htm
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Principle of Measurement
Particle migration Sedimentation or creaming Particle size variation Coalescence or flocculation

t=0 min t=15 min

t=0 min t=15 min

Testing for Stability

Monitor chemical changes

pH Loss of activity
Vitamins Antioxidants Enzymes Preservatives UV Filters

Photo-degradation of UV filters
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Testing for Stability

Monitor preservative efficacy

Initial challenge test to accepted protocols

CTFA, CTPA, B.P. and European Pharmacopoeias It is recommended that this be done if widemouthed container is used to assess risk of mould and fungal growth

Head space test

Challenge testing of stability samples

It is recommended that this be done after 3 months stability testing at RT and 40C

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Packaging Compatibility
STRESS CRACKING - The Hedley Test Applied to detergent/oil based products which are contained in polythene, PVC, PET. 12 samples filled to the declared volume and closure fitted to the correct torque. Stored at 60C for 48 hours, 6 upright and 6 inverted. At the end of the test no containers should show any signs of cracking.
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Packaging Problems

Panelling of polyethylene Dissolving of PVC Oils causing brittle polystyrene Corrosion of aluminium Discolouration of plastic Transpiration of perfume through plastic Absorption of actives by pack wall

Etc.
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Product Stability
What is it? How do we test it? How can we improve it?
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Emulsion Stability

A two-phase system, consisting of two completely immiscible or partially miscible liquids, one being dispersed in the other in the form of very fine droplets Water-in-Oil = w/o Oil-in-Water = o/w Oil-in-Water-in-Silicone = o/w/Si
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Emulsion Stability

What makes it stable?

Correct choice of emulsifier system Compatible ingredients Compatible pH Correct mixing method Compliance with specification Compatible packaging Understanding possible causes of instability
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Emulsion Stability

What makes it stable?

Correct choice of emulsifier system Compatible ingredients Compatible pH Correct mixing method Compliance with specification Compatible packaging Understanding possible causes of instability
John Woodruff; Creative Developments (Cosmetics) Ltd.

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HLB System
HLB Number = E + P 5 where E = molecular weight percent of ethylene oxide content P = molecular weight percent of polyol content In the equation above the value (E+P) can take on any value up to a maximum of 100. This means that the HLB number assigned to the emulsifier will lie within the range of 0 to 20.
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HLB System
HLB number of surfactant and type of emulsion formed < 3 none 3 8 water-in-oil (W/O) 8 15 oil-in-water (O/W) > 15 solubilisation

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Liquid Crystals
Some emulsifier systems form liquid crystal structures, which contribute to stability Examples: Cetearyl glucoside with cetearyl alcohol Sorbitan olivate and cetearyl olivate Sorbitan stearate with sorbityl laurate Sorbitan stearate with sucrose cocoate Polyglyceryl-3 methylglucose distearate Potassium cetyl phosphate and hydrogenated palm glycerides Lauryl glucoside & polyglyceryl-2 dipolyhydroxystearate
48 John Woodruff; Creative Developments (Cosmetics) Ltd.

Liquid Crystal Emulsion

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Liquid Crystal Emulsion

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Other Emulsifiers

Polymers e.g. Acrylates/C10-30 Alkyl Acrylate Crosspolymers Polyethylene glycol ethers (Oleth-10; Laureth-10 etc) Polysorbates with Sorbitan esters e.g. Polysorbate-20 with Sorbitan monolaurate Glyceryl esters e.g. Glyceryl cocoate / laurate etc. Alkolylated dimethicones (AKA Dimethicone copolyols) Soaps e.g. triethanolamine stearate; Potassium peanutate etc. PG Esters e.g. Propylene glycol myristate etc. Sucrose esters e.g. Sucrose laurate / myristate etc
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Emulsion Stability

What makes it stable?

Correct choice of emulsifier system Compatible ingredients Compatible pH Correct mixing method Compliance with specification Compatible packaging Understanding possible causes of instability
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Incompatible Ingredients

Carbomers and salts

Kathon CG contains a salt Many preservatives are formaldehyde donors

Dihydroxyacetone and formaldehyde

Enzymes and chelating agents

EDTA and its salts Parabens Ethoxylated emulsifiers

etc. etc.
John Woodruff; Creative Developments (Cosmetics) Ltd.

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pH vs Viscosity
Typical carbomer system
100000 98000 96000 94000 92000 90000 88000 86000 84000 pH 5.0 pH 5.5 pH 6.0 pH 6.5 pH 7.0 pH 7.5 pH 8.0
John Woodruff; Creative Developments (Cosmetics) Ltd.

Viscosity

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Correct Mixing Methods

Use laboratory mixing equipment which represents that available in the factory

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Pilot Scale

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Correct Mixing Methods

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Compliance with Specification

How was the specification set?

One small laboratory batch? 2 or more laboratory batches with reproducible results? Pilot scale batch?

Was stability tested on a product within the specification set?

Better still; were 2 or more batches at limits of specification tested

John Woodruff; Creative Developments (Cosmetics) Ltd.

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Emulsion Stability
What causes instability? For an emulsion to become unstable the dispersed phase droplets must collide and coalesce Coalescence of two dispersed phase droplets produces a bigger dispersed phase droplet, and the ultimate outcome of this process is complete phase separation, indicating emulsion instability
59 John Woodruff; Creative Developments (Cosmetics) Ltd.

Forces of Attraction
F = -Aa 12H where F = London-Van der Waals force of attraction A = Hamaker constant a = radius of the dispersed phase droplets H = distance between two adjacent dispersed phase droplets
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F = -Aa 12H

Forces of Attraction

Good stuff but what does it mean for emulsion stability From the equation it can be seen that the magnitude of the attractive force increases as the radius of the dispersed phase droplets becomes larger and less as the distance between them is increased Stability = Small droplets far apart
61 John Woodruff; Creative Developments (Cosmetics) Ltd.

Stokes Law
Stokes Law describes the factors influencing the velocity of a solid sphere, moving under the force of gravity, in a continuous liquid medium
V = 2a2(cd)g 9

V = velocity of the dispersed phase droplet a = radius of the dispersed phase droplet d = density of the dispersed phase c = density of the continuous phase g = acceleration due to gravity = viscosity of the continuous phase
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Stokes Law: Good stuff but what does it mean for emulsion stability
V = 2a2(cd)g 9 To improve stability reduce V

Reduce a - size of dispersed phase droplet Reduce (pc-pd) by matching density of the dispersed phase with that of the continuous phase g = acceleration due to gravity difficult to alter Increase - viscosity of the continuous phase
John Woodruff; Creative Developments (Cosmetics) Ltd.

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What droplet size?

Emulsion appearance and approximate particle size

milky-white greater than 1 blue-grey 1.0 - 0.1 translucent 0.1 - 0.05 transparent less than 0.05

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Emulsion Stability

Careful selection of emulsifiers Small droplet size (High shear mixing; PIT technology) Lamellar structures by using emulsifiers that form liquid crystals Match SG of oil phase to aqueous phase Adjust rheological properties by using carbomers or xanthan gum, starch or CMC derivatives etc.
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Add Rheological Additive

0% UltraThix P-100 + 0.5% Cerasynt 945 0.5% UltraThix P-100 + 0.2% Cerasynt 945

0.5% UltraThix P100 + 0.5% Cerasynt 945 Cerasynt 945 = Glyceryl stearate (&) laureth-23 Ultrathix P100 = Acrylic acid/VP Crosspolymer
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John Woodruff; Creative Developments (Cosmetics) Ltd.

Add Right Rheological Additive

Zinc Oxide nano particles

Carbomer
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Acrylic acid/VP Crosspolymer

John Woodruff; Creative Developments (Cosmetics) Ltd.

Microscope Examination
Titanium Dioxide Nano particles

Carbomer
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Acrylic acid/VP Crosspolymer

John Woodruff; Creative Developments (Cosmetics) Ltd.

Sun Protection Products

These present special problems

Emulsion stability Agglomeration of micronised sunscreens Crystallising of organic sunscreens Failure to meet SPF declaration Failure to meet UVA requirements Failure to meet water resistance claims Photodegradation of actives
John Woodruff; Creative Developments (Cosmetics) Ltd.

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Sun Protection Products

Agglomeration of micronised sunscreens can be seen under a microscope at 1000x magnification

Use rheology modifiers to stop migration of particles Veegum is good. Acrylic acid/VP Crosspolymer is recommended

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Preventing Agglomeration
TiO2 Nano particles Zinc Oxide nano particles

Acrylic acid/VP Crosspolymer

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Crystallising of Organic Sunscreens

Check solubility in oil phase

If using Phenylbenzimidazole Sulfonic Acid pH 7.3 - 7.7 is critical

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Photodegradation of BMDBM

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Improve UV Absorber Stability

The UVA filter BMDBM is not photostable and may lose 60% or more of its activity at 360nm when exposed to solar radiation. EHMC destabilises BMDBM / octocrylene mixtures Benzophenone-3 stabilises BMDBM weakly; octocrylene stabilises EHMC strongly but does not stabilise BMDBM and ethylhexyl methoxycrylene stabilises BMDBM strongly. There is a relationship between the rate of photo decay of BMDBM and the dielectric constant of the oil phase. As the dielectric constant increases BMDBM is progressively more stable until it reaches maximum stability at about 8.8, after which its rate of decay increases again

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Sun Protection Products

Failure to meet SPF declaration

Failure to meet UVA requirements

Study the suppliers literature and many articles on the subject

http://www.creative-developments.co.uk/papers/

http://www.cosmeticsbusiness.com/section.asp?navcode=50 Dont put to much faith in SPF boosters Use the Ciba Sunscreen Simulator then in-vitro then in-vivo Make sure the formula complies with latest EU Recommendation (UVA =>1/3rd UVB)

http://www.ciba.com/index/ind-index/ind-per_car/ind-pc-uv/ind-pc-uv-sss.htm

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John Woodruff; Creative Developments (Cosmetics) Ltd.

Thank you for your time and may all your creations be stable
John Woodruff www.creative-developments.co.uk

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