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.

If

consumers 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.

Regulatory

requirements 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!

Long way!
Very Hot!

From factory to
consumers homes our
products are subject to a
range of temperatures
during storage in
warehouses and
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.

As

an 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
Accelerated
Stability
(Pilot Batch)

Fragrance
Support

Standard
Accelerated
Stability
(Pilot Batch)

Stress Testing

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,C

P,C,M

8 weeks

P,C

P,C

12 weeks
13 Weeks for OTC

P,C,M

P,C

P Physical Characteristics (Color, Odor, Appearance)

C Chemical/Physical Characteristics (pH, Viscosity, %Actives)
M Microbiological Requirement
Sample Requirements:
Micro Requirements
Chemical/Physical

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

12 (1 at each pull point indicated above)

Signs of Physical Instability

Cracking within the formulation

Phase separation

Colour change

Yellowing very common when formulation contains amine

Odour

e.g. Creaming, Sedimentation

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
0
1
2
3
4
5

DESCRIPTION
OK
10% Cracking in shampoo texture
20% Cracking in shampoo texture
30% Cracking in shampoo texture
40% Cracking in shampoo texture
50% Cracking in shampoo texture or more

2) Phase Separation
SCORE
0
1
2
3
4
5

DESCRIPTION
OK
0.1 cm. of transparent level on top
0.2 cm. of transparent level on top
0.3 cm. of transparent level on top
0.4 cm. of transparent level on top
0.5 cm. of transparent level on top or more

Signs of Physical Instability

Shampoo samples scored according to SE Asia scale:

Sign = 1
Sep = 1

Sign = 3
Sep = 4

Sign = 2
Sep. = 2

Sign = 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
Idea

1.
Project Brief Technical
Section

Charter
sign-on

2.
Charter
-Technical
section

3.
Concept
Lock

Contract
sign-on

4.
Design
Lock

5.
Specification
Lock

Lab/Pilot
scale
stability
proven

Full scale
manufacture
stability
proven

Global
Charter Gate
Ongoing stability evaluation

Global
Contract Gate

Final stability

Regional Launch
Gate

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)

Inadequate processing

e.g. DLSS hydrolysis leads to production of laureth-3 which

increases viscosity

Change in fragrance
Fault in packaging

e.g. incomplete hydration of polymers such as Jaguar and Carbopol

can lead to increasing viscosity over time

Hydrolysis of ingredients

Specification definition

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%)
formulation it is critical that
DLSS (32%)
you understand the basic
Glycerin
chemistry associated with the
Polyox WSR 308
key ingredients.
Methocel 40-202
CAPB (28%)
By understanding the
Euperlan KE 3795
potential interactions between
Si macro emulsion
Tetrasodium EDTA (39%)
ingredients you can begin to
Fragrance
generate technical hypotheses
for the cause of the instability. Kathon CG
DMDM Hydontoin
Sodium Chloride (20%)
PPG-9

What are the emulsifiers

used in the silicone emulsion?
What else is in Euperlan, apart
from EGDS?
How might these additives
affect stability of the product?
(Euperlan KE 3795 contains
SLES-1EO and CAPB)

OH

The SLES Iceberg

Ethylene Oxide

OSO3Na

SLES 1EO is not a single pure molecule

O

Non ethoxylated material

OH
OH

OSO3Na
O

OH
O

Ethylene Oxide

OH

OH

n=3-12

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

OH
OH

O
O

OSO3Na

OH
O

OH

n=3-12

OSO3Na

OSO3Na

n=3-12

Distribution of EO units
Sulphur Trioxide
Non-ethoxylated material
NaOH
Distribution of alkyl chain lengths
Unsulphated material
+ NaCl?
Citric acid? NaSO4?
OSO3Na

Pack & Fragrance Interactions

Product stable in
glass container

Simple changes in packaging &

fragrance can lead to changes in
stability e.g. colour and odour

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
plastic
composition
Product in white
PE Bottle - unstable

Effect of
change in
plastic dye
Product in white
PP Bottle - stable

Product in coloured
PP Bottle - unstable

Effect of Processing
Bench scale

Pilot plant

Full scale
manufacture

Defined
formulation
& order of
addition

Defined
formulation
& order of
addition

Defined
formulation
& order of
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 (VS.)
0

18000

RT

16000

45

37
50

14000
12000

.
S
V

10000
8000
6000
4000
2000
0

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

ONa
O

[O

SO3 Na

CH2CH2 ] OH
n

+
HO

O
ONa

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

Viscosity (cP) ))

14000
12000
10000
8000
6000
2.2 wt% NH4Cl

4000

0.2 wt% NH4Cl

2000
0
0

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
Details

and results of stability testing

must be recorded

In

Port 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

Aid

tracking

to help schedule