Product Stability

Testing

Presented by
Ian Lyle (Port Sunlight)
Chadaporn Kusumarn (Shanghai)
Topics to be covered

 Why do we do stability testing?

 Stability test protocols & procedures

 Factors that can affect product stability

 Real life examples

 Data recording
Topics to be covered

 Why do we do stability testing?

 Stability test protocols & procedures

 Factors that can affect product stability

 Real life examples

 Data recording
Stability – Why Bother?
 World class brands are built on world class quality products.

 Ifconsumers experience low quality products (thin,

separated, malodour etc) they will be unlikely to buy them
again + it will affect their perception of the brand and their
expectations of other products within the brand.

 Regulatoryrequirements in some regions (e.g. EU requires

30 months shelf life for cosmetic products, during which they
must remain safe and fit for use)
Stability – Why Bother?
 The role of the product design team is to deliver consumer
preferred products that meet well defined physical performance
standards and specifications.

 The product must be able to be manufactured so that it maintains

its appearance and performance profile under a range of conditions
that it could realistically expect to experience during its life.
 During shipping
 Warehouse storage
 Consumer handling

 The purpose of stability testing is to ensure that a new or modified

product meets the intended physical, chemical and microbiological
quality standards as well as functionality and aesthetics when
stored under appropriate conditions
Factory to Consumer

Very Cold! From factory to

consumers’ homes our
products are subject to a
range of temperatures
Long way!
during storage in
warehouses and
Very Hot! transportation in trucks.

They can then sit on a

shelf in a shop for up to 2
years!
Topics to be covered

 Why do we do stability testing?

 Stability test protocols & procedures

 Factors that can affect product stability

 Real life examples

 Data recording
Stability Testing
 Our Stability Protocols are broken down into two main
categories of testing:

 General long term shelf life stability.

 Guidelines for this are well documented by the IFSCC, COLIPA and
ICH

 Short-term stress testing

 May require a series of several short tests that range from days to
weeks
 Light Stability
 Temperature Cycling
 Freeze/Thaw
 Not as well documented and can vary from region to region
 Dependent on SC conditions as well as weather extremes
Industry Guidelines
 Industry Guidelines published by IFSCC and COLIPA suggest that stability
be completed across a range. The range suggested is 4, 25, 37 and 45C
although some of the temperatures and ranges can be varied.

 The FDA in the USA bases their guidelines for Drug Expiration Dating on
the ICH Guidelines. The temperatures cited in the ICH Guidelines are
based primarily on a Global Climate Survey conducted by W. Grimm which
was an extensive study that included warehouse temperatures, extremes,
average temps and the number of days particular cities in various regions
were above the Mean Kinetic Temperature.

 Since 45C covers the worst case scenario for Long Term Product Stability
Testing and is in wide use throughout Unilever, the range suggested in the
COLIPA , IFSCC and ICH Guidelines are reasonable to recommend.
Stability of a Cosmetic Product

 Whether conducted in real time or under

accelerated conditions, tests should be
done in order to assure:
 stability
and physical integrity of cosmetic
products under appropriate conditions of
storage, transport and use
 chemical stability
 microbiological security
 compatibility between the contents and the
container.
Designing Stability Tests

 The design of the stability test/protocol is

dependent on the objective of the test.

 Asan example we may be interested in one or

more of the following objectives:
 assessment of the product contents
 assessment of the product-container compatibility
 comparison of a newly modified formula to an existing
stable product
 new manufacturing process
 new container
 changes in raw material supply or specification
Stability Protocol Overview
± 2 day Reference RT Control for Fragrance Standard Stress Testing
Accelerated Support Accelerated
Stability Stability
(Pilot Batch) (Pilot Batch)

Time 4o C ± 2o C 25o ± 2o C 37o ± 2o C 45°+ 2° C 50 C

INITIAL P,C,M
1 Week P,C
4 weeks P P,C P,C,M
8 weeks P P,C P,C
12 weeks P P,C,M P P,C
13 Weeks for OTC

P – Physical Characteristics (Color, Odor, Appearance)

C – Chemical/Physical Characteristics (pH, Viscosity, %Actives)
M – Microbiological Requirement

Sample Requirements:

Micro Requirements 6 (2 each at Initial, 45 & 1 mo, 25 & 3 mo)

Chemical/Physical 12 (1 at each pull point indicated above)
Signs of Physical Instability
 “Cracking” within the formulation
 Phase separation
 e.g. Creaming, Sedimentation
 Colour change
 Yellowing very common when formulation contains amine
 Odour
 Significant difference from control, base odour not covered

 Some attributes such as pH, viscosity and micro have well defined numerical
specification ranges, but others are more vague (“compare with standard”)
 Currently there are no fixed standards for what are acceptable and unacceptable
changes in physical characteristics – it is up to the judgment of individual
formulators.
 Category workshop planned in 2007 to begin to define common reference points
for these
Example: SE Asia Grading Scale
1) Sign of Separation
SCORE DESCRIPTION
0 OK
1 10% Cracking in shampoo texture
2 20% Cracking in shampoo texture
3 30% Cracking in shampoo texture
4 40% Cracking in shampoo texture
5 50% Cracking in shampoo texture or more
2) Phase Separation

SCORE DESCRIPTION
0 OK
1 0.1 cm. of transparent level on top
2 0.2 cm. of transparent level on top
3 0.3 cm. of transparent level on top
4 0.4 cm. of transparent level on top
5 0.5 cm. of transparent level on top or more
Signs of Physical Instability
Shampoo samples scored according to SE Asia scale:

Sign = 1 Sign = 2
Sep = 1 Sep. = 2

Sign = 3 Sign = 4
Sep = 4 Sep = 3
When to do stability testing
 Stability testing of the formulation (CUC) should be started as
soon as possible during product development, even if the full
formulation is not yet defined. This should allow early
identification of any fundamental issues that need to be
resolved as part of the product development process.

 Final stability testing must be done on final full scale

manufactured product in the final pack (CU) according to
the defined life test protocols and results recorded in a
database for reference.

 At the final stability stage there should be no intrinsic stability

issues due to the base formulation. At this stage you should
be looking for any unexpected interactions between
fragrance, formulation and pack.
 Project Execution
Ideas
Feasibility
Capability
Launch

Global Charter Contract

Idea 1 2 sign-on 3 4 sign-on
5

1. 2. 3. 4. 5.
Project Brief - Charter Concept Design Specification
Technical -Technical Lock Lock Lock
Section section
Lab/Pilot Full scale
scale manufacture
stability stability
proven proven

Global Global Regional Launch

Charter Gate Contract Gate Gate
Ongoing stability evaluation 4 Final stability 5

At Spec lock – final stability must be complete (full scale manufacture product
in final pack) with final ingredient and product specifications in InterSpec
Topics to be covered

 Why do we do stability testing?

 Stability test protocols & procedures

 Factors that can affect product stability

 Real life examples

 Data recording
Factors affecting stability
 Ingredient chemistry
 New ingredient (or more often a sub-component or impurity)
 Specification definition
 Inadequate processing
 e.g. incomplete hydration of polymers such as Jaguar and Carbopol
can lead to increasing viscosity over time
 Hydrolysis of ingredients
 e.g. DLSS hydrolysis leads to production of laureth-3 which
increases viscosity
 Change in fragrance
 Fault in packaging
 e.g. pinholes in aerosol can lining leading to corrosion
 New packaging (material and colour)
 Sunlight (for transparent packs)
 Formulation Chemistry
e.g. Dove shampoo formulation
DI Water
Carbopol Slurry (2%)
In order to solve any SLES-1 (25%)
instability problems with your Guar C13S
Sodium Hydroxide (50%) What are the emulsifiers
formulation it is critical that used in the silicone emulsion?
you understand the basic DLSS (32%)
What else is in Euperlan, apart
chemistry associated with the Glycerin from EGDS?
Polyox WSR 308 How might these additives
key ingredients.
Methocel 40-202 affect stability of the product?
CAPB (28%)
By understanding the Euperlan KE 3795
potential interactions between (Euperlan KE 3795 contains
Si macro emulsion SLES-1EO and CAPB)
ingredients you can begin to Tetrasodium EDTA (39%)
generate technical hypotheses Fragrance
for the cause of the instability. Kathon CG
DMDM Hydontoin
Sodium Chloride (20%)
PPG-9
 OH

The SLES Iceberg OSO3Na

Ethylene Oxide

SLES 1EO is not a single pure molecule Non ethoxylated material

OH

O OH
O O
OSO3Na
O
O OH

OH OH
O n=3-12
n
Ethylene Oxide
It is a cocktail of a mixture of small OSO 3Na of n=3-12
amounts
O Sulphur Trioxide
a variety of residual feedstock and by-products
n NaOH

OH Non ethoxylated material OSO3Na

OH
O O
O OSO3Na

O
O OH
OSO3Na n=3-12
O
OH n=3-12 n
O
n

Non-ethoxylated material
Sulphur Trioxide Distribution of EO units
NaOH
Unsulphated material Distribution of alkyl chain lengths
+ NaCl? OSO3NaCitric acid? NaSO4?
Pack & Fragrance Interactions
Simple changes in packaging &
fragrance can lead to changes in
Product stable in stability e.g. colour and odour
glass container

Effect of minor change in fragrance

Product with new

fragrance in glass
container - unstable
Effect of moving from glass to plastic

Effect of
change in Effect of
plastic change in
composition plastic dye

Product in white Product in white Product in coloured

PE Bottle - unstable PP Bottle - stable PP Bottle - unstable
Effect of Processing
Full scale
Bench scale Pilot plant manufacture
Defined Defined Defined
formulation formulation formulation
& order of & order of & order of
addition addition addition

Stable Stable Unstable

Making a product in the factory is very different from making it on

the bench. Simply increasing the scale and changing equipment
can impact on factors such as final microstructure which can
impact on product stability.

Beware hidden modifications in processing (e.g. temp, mixing

times etc).
Topics to be covered

 Why do we do stability testing?

 Stability test protocols & procedures

 Factors that can affect product stability

 Real life examples

 Data recording
Sunsilk Volume Combing Cream
● New Sunsilk Volume range launched in Europe Jan 2004 (Project
Einstein); combing cream had “ultra low fat” conditioner base with
performance superior to Kerastase.

● Storage testing done on samples from lab and pilot scale production;
no main plant trial done.

● At first production in Bydgoszcz, product viscosity was at lower end of

spec, did not build normally, and separation observed after 1-2 weeks.

● Fortunately, First Production routinely held in quarantine and product

spec had both “fresh” and “equilibrium” viscosities

● Crisis Team formed to find resolve issue and minimise launch delay

● Product had to be reformulated to make more robust to variation in

mixing intensity. Consumer test had to be repeated: fortunately results
were good!
AMET Dove Atlas Viscosity
RMD 029 (VİS.)
0
RT
18000
37
45
16000
50

14000

12000

10000
İS
.V

8000

6000

4000

2000

DAY

Stability problem
Significant increase in viscosity of shampoos with
6/4/3 surfactant base over time at high storage
temperatures
Hydrolysis of DLSS in 6/4/3
O
R [O CH2CH2 ] O
n R [O CH2CH2 ] OH
ONa n

O SO3 Na +
O
HO
ONa
O SO3 Na

 DLSS (Disodium Laureth-3 Sulphosuccinate) surfactant in 6/4/3 base is

prone to hydrolysis under low pH conditions.

 Hydrolysis leads to production of Laureth-3 and a decrease in pH

 Laureth-3 is incorporated into miceller structure of surfactant base leading

to development of longer wormlike micelles that lead to significant increase
in product viscosity
Increasing 6/4/3 viscosity

Loss of DLSS

Impact of fatty alcohol, acid, and DLSS consumption on micelle shape.

(Dickinson, 2004)
6/4/3 Viscosity instability solution
 Inclusion of 2% NaCl (much higher than normal ca. 0.5%) to
thicken shampoo and then viscosity adjusted via addition of
PPG.

 High salt level means that micelles are closer to their

maximum growth capacity when the shampoo is made.

 End results – hydrolysis still occurs but impact of increased

level of fatty alcohol on viscosity is significantly reduced by
higher salt level. (i.e. Formulation is now more robust.)
Stabilising 6/4/3 Shampoos
18000

16000

14000

12000
Viscosity (cP) ))

10000

8000

6000
2.2 wt% NH4Cl
4000
0.2 wt% NH4Cl
2000

0
0 1 2 3 4 5
o
Weeks at 49 C

Increasing salt level to 2% or above keeps

formulation viscosity stable at high temp.
Key learning points
 Key delivery from CTC is stable products under all relevant handling and
storage conditions

 Rigorous stability testing procedures are key to ensuring the integrity of

our products

 We have well defined stability evaluation protocols – better global

definition of acceptable vs unacceptable results to be agreed later this
year.

 Understanding the chemistry of formulations is key to finding the

technical cause of any instability and identifying a solution

 Cause of instability can range from molecular chemistry of a specific

ingredient to the way in which the whole product was manufactured –
detailed knowledge of product ingredients and manufacture is critical.
Topics to be covered

 Why do we do stability testing?

 Stability test protocols & procedures

 Factors that can affect product stability

 Real life examples

 Data recording
Data Recording

 Detailsand results of stability testing

must be recorded
 InPort Sunlight the plan is to do this
using FReg

Contact:
Rob Waight (Ext. 3219)
FReg and Stability Testing
 What are we doing now?
 Links to FReg:
 Formulations
 Ingredients
 Equipment

 How it might activitiesbe used:

 Modelling
 Sample tracking
 Aid to help schedule