product stabilityproduct stability - front...

1

Product StabilityProduct Stabilityoror HowHow toto make sure your product stays as good as newmake sure your product stays as good as new

John WoodruffJohn Woodruff

Creative Developments (Cosmetics) LtdCreative Developments (Cosmetics) Ltd

www.creative-developments.co.uk

2

Product StabilityProduct Stability

What is it?What is it?

How do we test it?How do we test it?

How can we improve it?How can we improve it?

3





John Woodruff; Creative Developments(Cosmetics) Ltd.4

Definition of StabilityDefinition of Stability

In mathematics, stability theory addresses theIn mathematics, stability theory addresses thestability of solutions of differential equations andstability of solutions of differential equations andof trajectories of dynamical systems under smallof trajectories of dynamical systems under smallperturbations of initial conditions.perturbations of initial conditions.

In probability theory, the stability of a randomIn probability theory, the stability of a randomvariable is the property that a linear combinationvariable is the property that a linear combinationof two independent copies of the variable hasof two independent copies of the variable hasthe same distribution, up to location and scalethe same distribution, up to location and scaleparameters. ...parameters. ...



-- the quality of being enduring and freethe quality of being enduring and freefrom change or variationfrom change or variation

-- resistant to change of position orresistant to change of position orconditioncondition

-- firm and dependable; subject to littlefirm and dependable; subject to littlefluctuationfluctuation

-- not taking part readily in chemicalnot taking part readily in chemicalchangechange



What do we understand about it with regard toWhat do we understand about it with regard tocosmetic products?cosmetic products?

That a product remainThat a product remain ““fit for purposefit for purpose””

AppearanceAppearance

Purity including lack of microbial contaminationPurity including lack of microbial contamination

EfficacyEfficacy

That it remains fit for purpose for a period of notThat it remains fit for purpose for a period of notless than 36 months from manufacture and notless than 36 months from manufacture and notless than its PAO declarationless than its PAO declaration

7

Examples of InstabilityExamples of Instability



ObviousObvious

Emulsion breakdownEmulsion breakdown

Perfume changesPerfume changes

Colour changesColour changes

Viscosity changesViscosity changes

Fungal growthFungal growth

Wax crystallisationWax crystallisation

Sediment in clear lotionsSediment in clear lotions



Less ObviousLess Obvious

pH changespH changes

Loss of activityLoss of activity

VitaminsVitamins

AntioxidantsAntioxidants

EnzymesEnzymes

PreservativesPreservatives

PhotoPhoto--degradation of UV filtersdegradation of UV filters

Microbial growthMicrobial growth


Emulsion CreamingEmulsion Creaming


4 days at room temperature 1 month at 45°C1 month at room temperature

4 days at room temperature 1 month at room temperature

1 month at 45°C

Emulsion BreakdownEmulsion Breakdown


Viscosity ChangesViscosity Changes

0

10

20

30

40

50

60

70

Initial 5 days 10 15 20 25 30 days

Increasing Decreasing Stable


Worst Nightmare!Worst Nightmare!

Atmospheric Mould Colonies


Crystal GrowthCrystal Growth

15






Testing for StabilityTesting for Stability

Prepare a pilot batch and store it in itsPrepare a pilot batch and store it in itsretail packaging and check that it remainsretail packaging and check that it remainsfit for purpose for a period of not less thanfit for purpose for a period of not less than36 months from manufacture and not less36 months from manufacture and not lessthan its PAO declaration!than its PAO declaration!

ImpracticalImpractical

What other options?What other options?


Testing SchedulesTesting Schedules

Examples of suitable schedules are givenExamples of suitable schedules are given

in the IFSCC Monographin the IFSCC Monograph

Boots publishes a scheme that itsBoots publishes a scheme that its

suppliers are expected to usesuppliers are expected to use -- GR10GR10

Distance Learning Course (DLC) includesDistance Learning Course (DLC) includes

suggestions in its module on stabilitysuggestions in its module on stability



IFSCC MonographIFSCC Monograph

4400 ambient humidityambient humidity -- retain as controlretain as control

202000 / 25/ 2500 ambient humidityambient humidity -- 60 months60 months

373700 ambient humidityambient humidity -- 6 months6 months

454500 ambient humidityambient humidity -- 3 months3 months

373700 && 80% relative humidity80% relative humidity -- 1 month1 month

Freeze / ThawFreeze / Thaw

Light exposureLight exposure



DLC RecommendationsDLC Recommendations


DLC RecommendationsDLC Recommendations

– 1 month assessment (all storage conditions)





– 1 year assessment (all storage conditions)

– 18 month assessment (5°C and RT storage conditions only)

– 2 year assessment (5°C and RT storage conditions only)

– 30 month assessment (5°C and RT only)

– 3 year assessment (5°C and RT storage conditions only).


Testing SchedulesTesting SchedulesBoots recommendation - Stability and final pack compatibility of all cosmeticand toiletry products should be assessed to establish that they are stableand that no separation, crystallisation, contamination, degradation or otherinstability occurs within the claimed product shelf life

40°C0°C to 30°CProducts sold in tropicalclimates

30°C0°C to 23°CProducts sold in temperateclimates

Must be safe to use,effective

and stable in final packfor at least 3 months at:

Must be safe to use,effective

and stable in final packfor at least 36 months at:

Stability Requirements

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.


What should be checked?What should be checked?


What is ImportantWhat is Important

Consider the function of the product under test anddecide whether or not the changes observed could affectthis

Consider the safety of the product under test and decidewhether or not the changes observed could affect this

Consider whether the changes observed affect theaesthetics of the product under test

Note under what storage conditions any changesobserved take place and try to relate these to theenvironment in which the product is to be sold

Look for significant trends in changes of productattributes


Talking PointsTalking Points

What is important for this product in thisWhat is important for this product in thispackaging for this market?packaging for this market?

Setting product specificationSetting product specification

Minimum and maximum for each parameterMinimum and maximum for each parameter

Why these numbers?Why these numbers?

Have products been prepared and tested atHave products been prepared and tested atextreme specification limits?extreme specification limits?

Release specifications / shelfRelease specifications / shelf--life specificationslife specifications

What matters?What matters?


Accelerated Testing for StabilityAccelerated Testing for Stability

Prepare a pilot batch and store it in its retailPrepare a pilot batch and store it in its retailpackaging:packaging:--

Room Temperature (RT) for 24 monthsRoom Temperature (RT) for 24 months

44°°C for 3 monthsC for 3 months

4040°°C for 3 monthsC for 3 months

44°°C/40C/40°°C Cycle for a number of cyclesC Cycle for a number of cycles

In a NIn a N--facing window or a light box for 3mfacing window or a light box for 3m



Monitor for changes in appearanceMonitor for changes in appearance(Subjective measurements)(Subjective measurements)

HomogeneityHomogeneity

ColourColour

Glass slidesGlass slides

MicroscopeMicroscope

Texture and skin feelTexture and skin feel

OdourOdour



Monitor emulsion stabilityMonitor emulsion stability(Physical changes)(Physical changes)

Emulsion breakdownEmulsion breakdown Creaming or settlingCreaming or settling

Glass slidesGlass slides –– aeration and density/opacityaeration and density/opacity

MicroscopeMicroscope –– droplet size changes; crystalsdroplet size changes; crystals

Viscosity changesViscosity changes

Rheological changesRheological changes

Centrifuge testsCentrifuge tests

TurbiscanTurbiscan

LumifugeLumifuge


Emulsion CreamingEmulsion Creaming

3 months at 40C 18 months at RT

What ways are available for quicker results


4 days at room temperature1 month at 45°C

1 month at room temperature

4 days at room temperature 1 month at 45°C1 month at room temperature

Microscope ExaminationMicroscope Examination


Viscosity ChangesViscosity Changes

These are actualviscosity graphsof 5 differentw/o emulsionsdiffering only inemulsifier used


Rheological ChangesRheological Changes

For suspensions measure yield valuesFor suspensions measure yield values

Yield value is the minimum force necessary toYield value is the minimum force necessary toinduce flowinduce flow

Measured using a rheometer or a BrookfieldMeasured using a rheometer or a BrookfieldDigital Viscometer with small sample adaptorDigital Viscometer with small sample adaptor

Yield values may be used to determine theYield values may be used to determine thesuspending power of a composition; verysuspending power of a composition; veryuseful when developing scrubsuseful when developing scrubs

http://www.connock.co.uk/articles_exfoliants.htmhttp://www.connock.co.uk/articles_exfoliants.htm


Accelerated Stability TestingAccelerated Stability Testing

CentrifugeCentrifuge 5 minutes or more at 5,000 rpm5 minutes or more at 5,000 rpm

UltracentrifugeUltracentrifuge A centrifuge designed to run at very high speeds andA centrifuge designed to run at very high speeds and

thus generate very high centrifugal force is called anthus generate very high centrifugal force is called anultracentrifuge.ultracentrifuge.

Suspensions which would settle only very slowly orSuspensions which would settle only very slowly ornot at all under gravity can be made to separatenot at all under gravity can be made to separatequickly in such a device!quickly in such a device!


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


The LumiFugeThe LumiFuge

The multisampleThe multisampleanalytical centrifugeanalytical centrifugeLUMiFugeLUMiFuge®® acceleratesacceleratesthe demixing process upthe demixing process upto 2300 times comparedto 2300 times comparedto traditional test tubeto traditional test tubetests. Stability tests andtests. Stability tests andshelfshelf--life determinationslife determinationsof original dispersions areof original dispersions areup to 2500 times fasterup to 2500 times fasterthan performed in a testthan performed in a test

tube under earth gravitytube under earth gravity..

http://www.lum-gmbh.com/pages/products/lumifuge/products_lumifuge.htm


TurbiscanTurbiscan

The Turbiscanmeasures transmittedand reflected lightpassing through asample and graphs theresults. Differencesover time are due tochanges in droplet sizeand distribution

www.formulaction.com/stab_lab_gb.htm

Particle size variation

Coalescence or flocculation

Particle migration

Sedimentation or creaming

t=0 min

t=15 min

t=0 min

t=15 min

Principle of Measurement



Monitor chemical changesMonitor chemical changes

pHpH

Loss of activityLoss of activity

VitaminsVitamins

AntioxidantsAntioxidants

EnzymesEnzymes

PreservativesPreservatives

UV FiltersUV Filters

PhotoPhoto--degradation of UV filtersdegradation of UV filters



Monitor preservative efficacyMonitor preservative efficacy

Initial challenge test to accepted protocolsInitial challenge test to accepted protocols

CTFA, CTPA, B.P. and European PharmacopoeiasCTFA, CTPA, B.P. and European Pharmacopoeias

Head space testHead space test

It is recommended that this be done if wideIt is recommended that this be done if wide--mouthed container is used to assess risk of mouldmouthed container is used to assess risk of mouldand fungal growthand fungal growth

Challenge testing of stability samplesChallenge testing of stability samples

It is recommended that this be done after 3 monthsIt is recommended that this be done after 3 monthsstability testing at RT and 40Cstability testing at RT and 40C


Packaging CompatibilityPackaging Compatibility

STRESS CRACKINGSTRESS CRACKING -- The Hedley TestThe Hedley Test

Applied to detergent/oil based products whichApplied to detergent/oil based products whichare contained in polythene, PVC, PET.are contained in polythene, PVC, PET.

12 samples filled to the declared volume and12 samples filled to the declared volume andclosure fitted to the correct torque.closure fitted to the correct torque.

Stored at 60Stored at 60°°C for 48 hours, 6 upright and 6C for 48 hours, 6 upright and 6inverted.inverted.

At the end of the test no containers should showAt the end of the test no containers should showany signs of cracking.any signs of cracking.


Packaging ProblemsPackaging Problems

Panelling of polyethylenePanelling of polyethylene

Dissolving of PVCDissolving of PVC

Oils causing brittle polystyreneOils causing brittle polystyrene

Corrosion of aluminiumCorrosion of aluminium

Discolouration of plasticDiscolouration of plastic

Transpiration of perfume through plasticTranspiration of perfume through plastic

Absorption of actives by pack wallAbsorption of actives by pack wall Etc.Etc.

42






Emulsion StabilityEmulsion Stability

A two-phase system, consisting of twocompletely immiscible or partially miscibleliquids, one being dispersed in the other inthe form of very fine droplets

Water-in-Oil = w/o

Oil-in-Water = o/w

Oil-in-Water-in-Silicone = o/w/Si



What makes it stable?What makes it stable?

Correct choice of emulsifier systemCorrect choice of emulsifier system

Compatible ingredientsCompatible ingredients

Compatible pHCompatible pH

Correct mixing methodCorrect mixing method

Compliance with specificationCompliance with specification

Compatible packagingCompatible packaging

Understanding possible causes of instabilityUnderstanding possible causes of instability


HLB SystemHLB 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 anyvalue up to a maximum of 100. This means that the HLBnumber assigned to the emulsifier will lie within therange of 0 to 20.


HLB SystemHLB System

HLB number of surfactant and type ofemulsion formed

< 3 none

3 – 8 water-in-oil (W/O)

8 – 15 oil-in-water (O/W)

> 15 solubilisation


Liquid CrystalsLiquid Crystals

Some emulsifier systems form liquid crystal structures,Some emulsifier systems form liquid crystal structures,which contribute to stabilitywhich contribute to stability

Examples:Examples:

Cetearyl glucoside with cetearyl alcoholCetearyl glucoside with cetearyl alcohol

Sorbitan olivate and cetearyl olivateSorbitan olivate and cetearyl olivate

Sorbitan stearate with sorbityl laurateSorbitan stearate with sorbityl laurate

Sorbitan stearate with sucrose cocoateSorbitan stearate with sucrose cocoate

PolyglycerylPolyglyceryl--3 methylglucose distearate3 methylglucose distearate

Potassium cetyl phosphate and hydrogenated palmPotassium cetyl phosphate and hydrogenated palmglyceridesglycerides

Lauryl glucoside & polyglycerylLauryl glucoside & polyglyceryl--2 dipolyhydroxystearate2 dipolyhydroxystearate


Liquid Crystal EmulsionLiquid Crystal Emulsion


Other EmulsifiersOther Emulsifiers

Polymers – e.g. Acrylates/C10-30 Alkyl AcrylateCrosspolymers

Polyethylene glycol ethers (Oleth-10; Laureth-10 etc)

Polysorbates with Sorbitan esters e.g. Polysorbate-20with Sorbitan monolaurate

Glyceryl esters e.g. Glyceryl cocoate / laurate etc.

Alkolylated dimethicones (AKA Dimethicone copolyols)

Soaps e.g. triethanolamine stearate; Potassiumpeanutate etc.

PG Esters e.g. Propylene glycol myristate etc.

Sucrose esters e.g. Sucrose laurate / myristate etc


Incompatible IngredientsIncompatible Ingredients

Carbomers and saltsCarbomers and salts

Kathon CG contains a saltKathon CG contains a salt

Dihydroxyacetone and formaldehydeDihydroxyacetone and formaldehyde

Many preservatives are formaldehyde donorsMany preservatives are formaldehyde donors

Enzymes and chelating agentsEnzymes and chelating agents

EDTA and its saltsEDTA and its salts

ParabensParabens

EthoxylatedEthoxylated emulsifiersemulsifiers etc. etc.etc. etc.


pH vs ViscositypH vs Viscosity

84000

86000

88000

90000

92000

94000

96000

98000

100000

pH 5.0 pH 5.5 pH 6.0 pH 6.5 pH 7.0 pH 7.5 pH 8.0

Viscosity

Typical carbomer system


Correct Mixing MethodsCorrect Mixing Methods

Use laboratoryUse laboratory

mixing equipmentmixing equipment

which representswhich represents

that availablethat available

in the factoryin the factory


Pilot ScalePilot Scale


Correct Mixing MethodsCorrect Mixing Methods


Compliance with SpecificationCompliance with Specification

How was the specification set?How was the specification set? One small laboratory batch?One small laboratory batch?

2 or more laboratory batches with2 or more laboratory batches withreproducible results?reproducible results?

Pilot scale batch?Pilot scale batch?

Was stability tested on a product withinWas stability tested on a product withinthe specification set?the specification set? Better still; were 2 or more batches at limitsBetter still; were 2 or more batches at limits

of specification testedof specification tested



What causes instability?What causes instability?

For an emulsion to become unstable thedispersed phase droplets must collide andcoalesce

Coalescence of two dispersed phasedroplets produces a bigger dispersedphase droplet, and the ultimate outcomeof this process is complete phaseseparation, indicating emulsion instability


Forces of AttractionForces 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 dispersedphase droplets


Forces of AttractionForces of Attraction

Good stuff but what does it mean forGood stuff but what does it mean foremulsion stabilityemulsion stability

From the equation it can be seen that themagnitude of the attractive force increases

as the radius of the dispersed phasedroplets becomes larger and less as the

distance between them is increased

Stability = Small droplets far apart

F = -Aa–––12H


Stokes’ Law

Stokes Law describes the factors influencing the velocityof a solid sphere, moving under the force of gravity, in acontinuous liquid medium

V = 2a2(ρc–ρd)g–––––––––––––

9μ

V = velocity of the dispersed phase droplet a = radius of the dispersed phase droplet ρd = density of the dispersed phase ρc = density of the continuous phase g = acceleration due to gravity μ = viscosity of the continuous phase


Stokes Law: Good stuff but whatStokes Law: Good stuff but whatdoes it mean for emulsion stabilitydoes it mean for emulsion stability

V = 2a2(ρc–ρd)g

–––––––––––––

9μ

To improve stability reduce V

Reduce a - size of dispersed phase droplet

Reduce (pc-pd) by matching density of the dispersedphase with that of the continuous phase

g = acceleration due to gravity – difficult to alter

Increase μ - viscosity of the continuous phase


What droplet size?What droplet size?

Emulsion appearance and approximateparticle size

milky-white greater than 1μ

blue-grey 1.0 - 0.1 μ

translucent 0.1 - 0.05 μ

transparent less than 0.05 μ



Careful selection of emulsifiersCareful selection of emulsifiers

Small droplet size (High shear mixing; PITSmall droplet size (High shear mixing; PITtechnology)technology)

Lamellar structures by using emulsifiersLamellar structures by using emulsifiersthat form liquid crystalsthat form liquid crystals

Match SG of oil phase to aqueous phaseMatch SG of oil phase to aqueous phase

Adjust rheological properties by usingAdjust rheological properties by usingcarbomers or xanthan gum, starch or CMCcarbomers or xanthan gum, starch or CMCderivatives etc.derivatives etc.


Add Rheological AdditiveAdd Rheological Additive

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

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

0.5%UltraThix™ P-100+ 0.5%Cerasynt 945

Cerasynt 945 = Glyceryl stearate (&)laureth-23 Ultrathix P100 =

Acrylic acid/VP Crosspolymer


Add Right Rheological AdditiveAdd Right Rheological Additive

Zinc Oxide nano particles

Carbomer Acrylic acid/VP Crosspolymer


Microscope ExaminationMicroscope Examination

Titanium Dioxide Nano particles

Carbomer Acrylic acid/VP Crosspolymer


Sun Protection ProductsSun Protection Products

These present special problemsThese present special problems

Emulsion stabilityEmulsion stability

Agglomeration of micronised sunscreensAgglomeration of micronised sunscreens

Crystallising of organic sunscreensCrystallising of organic sunscreens

Failure to meet SPF declarationFailure to meet SPF declaration

Failure to meet UVA requirementsFailure to meet UVA requirements

Failure to meet water resistance claimsFailure to meet water resistance claims

Photodegradation of activesPhotodegradation of actives



Agglomeration of micronised sunscreens canAgglomeration of micronised sunscreens canbe seen under a microscope at 1000xbe seen under a microscope at 1000xmagnificationmagnification

Use rheology modifiers to stop migration ofUse rheology modifiers to stop migration ofparticlesparticles –– Veegum is good.Veegum is good. Acrylic acid/VPCrosspolymer is recommended


Preventing AgglomerationPreventing Agglomeration

Zinc Oxide nano particles

Acrylic acid/VP Crosspolymer

TiO2 Nano particles


Crystallising of Organic SunscreensCrystallising of Organic Sunscreens

Check solubility in oil phase

If using Phenylbenzimidazole Sulfonic AcidpH 7.3 - 7.7 is critical


Photodegradation of BMDBMPhotodegradation of BMDBM


Improve UV Absorber StabilityImprove UV Absorber Stability

The UVA filter BMDBM is not photostable and may lose 60% orThe UVA filter BMDBM is not photostable and may lose 60% or

more of its activity at 360nm when exposed to solar radiation.more of its activity at 360nm when exposed to solar radiation.

EHMC destabilises BMDBM / octocrylene mixturesEHMC destabilises BMDBM / octocrylene mixtures

BenzophenoneBenzophenone--3 stabilises BMDBM weakly; octocrylene stabilises3 stabilises BMDBM weakly; octocrylene stabilises

EHMC strongly but does not stabilise BMDBM and ethylhexylEHMC strongly but does not stabilise BMDBM and ethylhexyl

methoxycrylene stabilises BMDBM strongly.methoxycrylene stabilises BMDBM strongly.

There is a relationship between the rate of photo decay of BMDBMThere is a relationship between the rate of photo decay of BMDBM

and the dielectric constant of the oil phase. As the dielectricand the dielectric constant of the oil phase. As the dielectric

constant increases BMDBM is progressively more stable until itconstant increases BMDBM is progressively more stable until it

reaches maximum stability at about 8.8, after which its rate ofreaches maximum stability at about 8.8, after which its rate of

decay increases againdecay increases again



Failure to meet SPF declarationFailure to meet SPF declaration

Failure to meet UVA requirementsFailure to meet UVA requirements

Study the suppliers literature and many articles on theStudy the suppliers literature and many articles on thesubjectsubject

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

http://www.cosmeticsbusiness.com/section.asp?navcode=50http://www.cosmeticsbusiness.com/section.asp?navcode=50

DonDon’’t put to much faith in SPF boosterst put to much faith in SPF boosters

Use the Ciba Sunscreen Simulator then inUse the Ciba Sunscreen Simulator then in--vitro then invitro then in--vivovivo

http://http://www.ciba.com/index/indwww.ciba.com/index/ind--index/indindex/ind--per_car/indper_car/ind--pcpc--uv/induv/ind--pcpc--uvuv--sss.htmsss.htm

Make sure the formula complies with latest EUMake sure the formula complies with latest EURecommendation (UVA =>1/3Recommendation (UVA =>1/3rdrd UVB)UVB)

76

Thank you for your timeThank you for your timeand may all your creationsand may all your creations

be stablebe stable

John WoodruffJohn Woodruff

www.creativewww.creative--developments.co.ukdevelopments.co.uk

product stabilityproduct stability - front...

Documents