Beruflich Dokumente
Kultur Dokumente
Testing
Presented by
Ian Lyle (Port Sunlight)
Chadaporn Kusumarn (Shanghai)
Topics to be covered
Why
do we do stability testing?
Stability
Factors
Real
life examples
Data
recording
Topics to be covered
Why
do we do stability testing?
Stability
Factors
Real
life examples
Data
recording
If
Regulatory
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
Factors
Real
life examples
Data
recording
Stability Testing
Guidelines for this are well documented by the IFSCC, COLIPA and
ICH
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
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.
As
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
Colour change
Odour
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
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
Sign = 1
Sep = 1
Sign = 3
Sep = 4
Sign = 2
Sep. = 2
Sign = 4
Sep = 3
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
Factors
Real
life examples
Data
recording
Ingredient chemistry
New ingredient (or more often a sub-component or impurity)
Inadequate processing
Change in fragrance
Fault in packaging
Hydrolysis of ingredients
Specification definition
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
OH
Ethylene Oxide
OSO3Na
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
Product stable in
glass container
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
Topics to be covered
Why
do we do stability testing?
Stability
Factors
Real
life examples
Data
recording
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
[O
CH2CH2 ] O
n
ONa
O
[O
SO3 Na
CH2CH2 ] OH
n
+
HO
O
ONa
SO3 Na
Loss of DLSS
Viscosity (cP) ))
14000
12000
10000
8000
6000
2.2 wt% NH4Cl
4000
2000
0
0
Weeks at 49 C
Key delivery from CTC is stable products under all relevant handling and
storage conditions
Topics to be covered
Why
do we do stability testing?
Stability
Factors
Real
life examples
Data
recording
Data Recording
Details
In
Contact:
Rob Waight (Ext. 3219)
How
Modelling
Sample
Aid
tracking
to help schedule