Facing the Challenges of
Formulating
Christopher Johnson Christopher
Christopher Johnson ‐
Johnson ‐ Kinetik Technologies
Kinetik Technologies
SCC Ontario Chapter SCC Ontario Chapter –– 2008 Education Day
September 18, 2008
good is to:
black
hot
bad
white
cold
organic
i
i (A i lt )
non‐organic (Agriculture)
non‐
inorganic (Chemistry)
unnatural
chemical
synthetic
y
supernatural
Adj ti
Adjective
1. existing in or formed by (opposed to artificial)
2. based on the state of things in ; constituted by 3. in a state of in a state of
; uncultivated, as land
; uncultivated, as land Physical world, including living Physical world, including living organisms excluding
organisms excluding
manufactured objects from human interaction
manufactured objects from human interaction
unnatural
Coming from nature >> harvest, collection
Synthetic:
Plant
Animal
Soil
Olive Oil
Milk
Petroleum
Saponification
Fermentation
Cracking
Glycerin
Cheese
Gasoline
• Growing concerns regarding the fate of our planet (Global Warming, Pollution, Fuel Crisis, etc.)
• Increased demand for alternative fuel sources, organic foods and sustainable business practices (reduced ‘carbon footprint’)
• Increased consumer awareness is resulting in rapid growth (15% in 2005) of h(
) f
personal care
l
• Signifies major shift in consumer culture
• No official definition for personal care
y
g
• Limited formulatory access to ingredients or unethical behavior leading to products with conventional ingredients
• Limited knowledge of consumers makes it easier to make claims as a marketing tool without corresponding formulating effort
d f
l
ff
• Consumers believe ingredients used in
personal care are:
personal care are:
– Safer to use on themselves and their families
– Promoting
Promoting overall health & well‐
Promoting overall health & well
overall health & well‐
well‐being
– Better for the environment
• The reality is…
The reality is
ingredients are not always safe
– Finished products are costly to produce
Finished products are costly to produce
– Often inferior in performance
– Challenging to formulate
Ch ll i t f
l t
– Problems with large scale manufacturing
• aa chemical philosophy encouraging the design chemical philosophy encouraging the design
of products and processes that reduce or eliminate the use and generation of hazardous
eliminate the use and generation of hazardous substances
• Raw materials considered 2.
3.
4
4.
5.
should be:
made up of building blocks and be produced
produced using environmentally sound processes using environmentally sound processes
Efficient: Run chemical reactions at ambient Efficient: Run chemical reactions at ambient temperature and pressure to reduce energy waste
Safe: Safe: should not be suspected of causing human should not be suspected of causing human health or environmental risk
S t i bl biodegradable and derived from Sustainable: biodegradable and derived from Sustainable: bi d
d bl
dd i df
renewal vegetal feed stocks Responsible:
p
no animal testing in its development g
p
(unique to cosmetics)*
(unique to cosmetics)*
a set of guidelines to help define the term
the term as
as it applies to it applies to
personal care
• All
All products that are labeled or branded products that are labeled or branded
must:
– Be made with at least 95% all Be made with at least 95% all
ingredients
– Contain only synthetic ingredients specifically allowed under this standard and environmentally
allowed under this standard and environmentally
environmentally‐‐
friendly products that are nurturing to us and as harmless as possible to the earth
• What is ?
– Ingredients that come or are made from a I
di t th t
d f
renewable resource found in (flora, fauna, mineral)
mineral), with absolutely no petroleum with absolutely no petroleum
compounds. • Ingredients that are prohibited:
– Ingredients that have suspected human health risks as indicated by peer
indicated by peer‐‐reviewed third
reviewed third‐‐party scientific literature
– Incorporate synthetic silicone or petroleum compounds
p
y
p
p
• Parabens Parabens –– Synthetic preservatives that are potential endocrine disrupters
endocrine disrupters
• Sodium Sodium Lauryl
Lauryl Sulfate Sulfate –– Harsh cleansing agent
• Petrolatum/Mineral Oil/Paraffin Petrolatum/Mineral Oil/Paraffin –– Non
Non‐‐renewable byproducts of crude oil
• Chemical Sunscreens (Avobenzone
Chemical Sunscreens (Avobenzone//Oxybenzone
Oxybenzone) ) ––
Synthetic sunscreens
Synthetic sunscreens
• Glycols Glycols –– Petroleum derived synthetic chemicals
• Phthalates –
Phthalates – Synthetic fragrance components that are Phthalates
Synthetic fragrance components that are
potential toxins
• Ethoxylated Ingredients ‐
Ethoxylated Ingredients ‐ Ingredients that are made in part with ethylene oxide, • Ethanolamines – Foam and viscosity boosting ingredients that can interact with other ingredients to form
that can interact with other ingredients to form nitrosamines, a known carcinogen(37)
• Synthetic polymers (PVP/
Synthetic polymers (PVP/Acrylates
Acrylates) ) ‐‐ may contain residual hydrocarbons ‐ widespread
hydrocarbons ‐
hydrocarbons widespread organic pollutants
organic pollutants
• Formaldehyde Donors (DMDM Hydantoin
Formaldehyde Donors (DMDM Hydantoin/ / Diazolidinyl
Diazolidinyl
Urea/ Methylisothiazolinone
Urea/ Methylisothiazolinone) ) –– Preservatives that work by releasing formaldehyde
• Allowed synthetic ingredients Allowed synthetic ingredients –– those temporarily allowed in the initial phase of this standard:
– Non
Non‐‐paraben, non
paraben, non‐‐formaldehyde
formaldehyde‐‐donating synthetic preservatives
– Non
N ‐phthalate, non
Non‐
phthalate, non‐
hh l
‐irritating synthetic fragrances
i i i
h i f
– Quaternary anti
Quaternary anti‐‐static hair conditioners
– Coco Coco Betaine
Betaine
i
•
P hibit d i
Prohibited ingredients: di t
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Ammonium Lauryl Sulfate Amodimethicone
Behentrimonium Methosulfate
Butylene glycol Carbomer
Ceteareth‐20 Cetrimonium Chloride Coco DEA Cocoamidopropyl Betaine
Cyclopentasiloxane
Diazolidinyl Urea
Dimethicone
Disodium Cocoamphodiacetate
EDTA
EthylHexylGlycerin
Glycereth‐7 Cocoate
Isoceteth 20
Isopropyl Palmitate
Lauramide MEA
Lauryl DEA
•
P hibit d i
Prohibited ingredients: di t
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Methoxycinnamate
Olefin Sulfonate
Oleyl Betaine
Parabens (methyl, propyl, butyl, etc.)
PEG‐150 Distearate
PEG‐7 Glyceryl Cocoate Polyquaternium 10 Propylene Glycol Sodium Cocoyl Sarcosinate
Sodium Hydroxymethylglycinate
Sodium Laureth Sulfate Sodium Lauroyl Sarcosinate
Sodium Lauryl Carboxylate
Sodium Lauryl Sulfate Sodium Lauryl Sulfoacetate
Sodium Myreth Sulfate Sodium PCA or Na PCA (pyrrolidone carbonic acid) Soyamidopropalkonium Chloride
Stearamidopropyl
d
l Dimethyl
h l Amine INCI: Purified Water, Aloe Barbadensis
INCI:
Purified Water Aloe Barbadensis Leaf Leaf
Juice, Sodium Lauryglucosides
Hydroxypropylsulfonate, Cocamidopropyl
Cocamidopropyl
Betaine, Decyl Glucoside, Glycerin, Guar Betaine
Guar Hydroxypropyltrimonium Chloride, Hydroxypropyltrimonium Chloride
Panthenol, Allantoin, Simmondsia Chinensis
(Jojoba) Seed Oil(2), Helianthus Annuus
(Sunflower) Seed Oil(3) Olea Europaea
(Sunflower) Seed Oil(3), Olea
(Olive) Fruit Oil(3), Linum Usitatissimum
(Linseed*) Seed Oil(4), Borago Officinalis
Seed Oil(3), Vitis Vinifera (Grape) Seed Oil(4), Rosa Canina
l( )
Fruit Oil(4), Citric Acid, l( )
d
Polysorbate 20
20, Sodium Benzoate, Potassium Sorbate, Ethylhexylglycerin.
• List of Allowed Ecological Processes – Saponification of vegetable oils to make soap
– Hydrolysis of Proteins into Amino Acids
Hydrolysis of Proteins into Amino Acids
– Fat
Fat‐‐Splitting of vegetable oils to produce glycerin and fatty acids
– Hydrogenation of oils Hydrogenation of oils
– Hydrogenolysis of methyl esters to products fatty alcohols – Glucosidation of fatty Alcohols and glucose
– Sulfation of fatty alcohol
– Protein fragment Protein fragment acylation
acylation
– Etherificiation of glycerin making of glycerin making polyglycerol
gy
gp
polyglycerol
yg y
– Esterification or or Transesterification
Transesterification to produce esters
• Polyglyceryl esters – 100% vegetable
100% vegetable‐‐based
– Based on Chemistry
– Esterification of of polyglycerol
polyglycerol with fatty acids – Functional emulsifiers & surfactants
– Wide range of HLBs for O/W & W/O emulsions
g
/
/
– PEG
PEG‐‐Free, biodegradable & free of toxic impurities
INCI
Function
Polyglyceryl‐‐3 Stearate
Polyglyceryl
O/W
O/W‐‐Emulsifier
Polyglyceryl‐‐3 Polyricinoleate
Polyglyceryl
W/O
W/O‐‐Emulsifier
Polyglyceryl‐‐10 Laurate
Polyglyceryl
10 Laurate
Solubilization
Polyglyceryl‐‐5 Oleate
Polyglyceryl
Emulsifier (Oil gel)
Polyglyceryl‐10 Laurate
(Solubilizer)
20
18
16
14
Polyglyceryl‐5 Oleate
(O/W‐Emulsifier)
12
10
Polyglyceryl‐3 Stearate
P
l l
l 3 St
t
(O/W‐Emulsifier)
8
6
4
2
0
Polyglyceryl‐3 Polyricinoleate
(W/O‐Emulsifier)
10
C‐8
Fatty acid
9
C‐10
C‐12
8
7
C‐14
6
C‐16
C‐18
2 x C‐18
2 C 18
2
Polyricinoleate
5
4
3
g
y
Degree
of Polymerization
HLB-Value
20
18
Polyglyceryl 3 Stearate
Polyglyceryl‐3
Stearate
(O/W Emulsifier)
16
14
12
10
8
6
4
2
0
10
C‐8
Fatty acid
9
C‐10
C‐12
8
7
C‐14
6
C‐16
C‐18
2 x C‐18
2 C 18
2
Polyricinoleate
5
4
3
g
y
Degree
of Polymerization
HLB-Value
•
•
•
•
•
•
non‐ionic O/W Emulsifier
non‐
vegetable origin
vegetable origin
HLB: ~ 10 –
HLB: ~ 10 – 12
use level: 2 ‐
use level: 2 l l 2 ‐ 4 %
4%
optimal pH: 5 –
optimal pH: 5 – 8
oilphase 15 ‐
oilphase 15 ‐ 30 %
• Formulating Tips:
Formulating Tips:
– Melt in oil phase 65 –
Melt in oil phase 65 – 80 80 °°C
– Increased viscosity with increased emulsifier Increased viscosity with increased emulsifier
level, slight viscosity increase during storage
– Poor compatibility with electrolytes
Poor compatibility with electrolytes
– Typical combination with Sodium Stearoyl Lactylate
Lactylate*
– Support stability with Glyceryl Stearate, fatty alcohol, fatty acids and/or Xanthan Gum
alcohol, fatty acids and/or Xanthan Gum
•
•
•
•
•
•
anionic O/W Co
anionic O/W Co‐‐Emulsifier
vegetable origin
vegetable origin
HLB: > 10 (depending on pH)
use level: up to 3%
l l
t 3%
optimal pH: 5 –
optimal pH: 5 – 7
oil phase 15 –
oil phase 15 – 30%
• Formulating Tips:
– Melt in oil phase 65 –
Melt in oil phase 65 p
– 80 80 °°C
– Support stability with Glyceryl Stearate, fatty alcohol, fatty acids and / or Xanthan Gum
– Slight downshift of pH may be observed after emulsification
Certain molecules in a formulation (e.g. essential oils) may interact with the interphase of an emulsion droplet
Oil Phase
Oil Phase
Water Phase
Water Phase
That can potentially result in a destabilization of the emulsion
That can potentially result in a destabilization of the emulsion
Oil Phase
Oil Phase
Water Phase
Water Phase
Using mixtures of non
U
Using mixtures of non‐
i
i
f
‐ionic and anionic emulsifiers can i i
ionic and anionic emulsifiers can improve d i i
l ifi
i
improve stability of the emulsion
stability of the emulsion
Polyglyceryl‐‐3 Stearate
Polyglyceryl
‐ Na+
Sodium Stearoyl Lactylate
Sodium Stearoyl Lactylate
Ionic co‐
Ionic co‐emulsifiers create a layer of organized water molecules to protect the interphase
Oil Phase
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Na+
‐
N +
Na
‐
Na+
‐
Na+
‐
Na+
‐
Na+
Water Phase
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Page 41 ∙Biesterfeld product training seminar27‐28.08.2008
Phase
Ingredient INCI
A
Deionised Water
B
C
D
Supplier
%
68.00
Sodium Phytate
Dr.Straetmans
0.10
Glycerin
y
Various
3.00
Glyceryl Caprylate
Dr. Straetmans
0.70
p‐Anisic Acid
Dr. Straetmans
0.20
Xanthan Gum
Kelco
0.25
M
Magnesium Aluminium Silicate i
Al i i
Sili t
R T V d bilt
R.T. Vanderbilt 05
0.5
Polyglyceryl‐3 Stearate
Dr. Straetmans
3.00
Sodium Stearoyl Lactylate
Dr.Straetmans
2.00
Glyceryl Stearate
Cognis
3.00
Cetyl Alcohol
Cognis
2.00
Butyrospermum Parkii (Shea Butter)
Kinetik
2.00
Decyl Cocoate Evonik
6.00
Caprylic/Capric Triglyceride py / p
gy
Various
5.00
Squalane Various 3.00
Tocopherol, Helianthus Annuus (Sunflower) Seed Oil
Dr. Straetmans
0.05
Tocopheryl Acetate
Dr. Straetmans
1.00
Fragrance (Natural)
Fragrance (Natural)
Various
0 20
0.20
Citric Acid (20% sol.)
Various
q. s. Formula #
L016‐05‐1007
100.00
• Emulsion properties:
l
– white viscous cream
– pH: 5.0 pH: 5.0 –– 5.5
– viscosity: ~ 35,000 cps
– stability: > 3 months @ 40, 20 & 4
stability: > 3 months @ 40, 20 & 4°°C
– passes micro challenge
20
18
Polyglyceryl‐3 Polyricinoleate
P
l l
l 3P l i i l t
(W/O‐Emulsifier)
16
14
12
10
8
6
4
2
0
10
C‐8
Fatty acid
9
C‐10
C‐12
8
7
C‐14
6
C‐16
C‐18
2 x C‐18
2 C 18
2
Polyricinoleate
5
4
3
g
y
Degree
of Polymerization
HLB-Value
•
•
•
•
•
•
non‐ionic W/O Emulsifier
non‐
vegetable origin
HLB: ~ 4 HLB: ~ 4 –– 5
use level: 3 – 6 %
use level: 3 6%
wide range of viscosity from creme to lotion
up to 80 % waterphase
• Suitable stabilizing / thickening systems
– ZnSO4 or MgSO4
– Mg Stearate or Zn Stearate
– Bentonite
– Hydrogenated Castor Oil
– Beeswax
– Carnauba Wax
Page 46 ∙Biesterfeld product training seminar27‐28.08.2008
• Formulating
Formulating Tips:
Tips:
– Viscosity can be increased by:
• llowering oil concentration
i
il
t ti
• lowering polarity of oil
• increasing amount of W/O
increasing amount of W/O‐
/ ‐emulsifier
– Additional factors:
• emulsification temperature > 75
emulsification temperature > 75°°C
• slow stirring during cooling
• homogenization at < 45°
homogenization at < 45°C
Phase
Ingredient INCI
g
A
Deionised Water
B
B1
C
Supplier
pp
%
55.25
Glycerin
Various
7.00
Zinc Sulfate
Various
1.00
Glyceryl Caprylate
Dr. Straetmans
0.70
p‐Anisic
Dr. Straetmans
0.20
Citric Acid (20% sol)
Various
q. s.
P l l
Polyglyceryl‐3‐Polyricinoleate
l3P l i i l t
D St t
Dr. Straetmans
5 00
5.00
Cera Alba
Kahl & Co
4.00
Helianthus Annuus (Sunflower) Seed Oil
Various
16.00
Tocopherol, Helianthus Annuus (Sunflower) Seed Oil
Dr. Straetmans
0.20
Magnesium Stearate
Various
0.50
Caprylic/Capric Triglyceride
Sasol
10.00
Fragrance (Natural)
Formula # L019‐30B‐108
0.15
100.00
• Emulsion properties:
l
– thick white cream
– viscosity: ~ 60,000 –
viscosity: ~ 60,000 – 100,000 cps
– stability: > 3 months @ 40
stability: > 3 months @ 40, 20 & 4
, 20 & 4°°C
– passes micro challenge
20
18
Polyglyceryl 5 Oleate
Polyglyceryl‐5
Oleate
(O/W‐Emulsifier)
16
14
12
10
8
6
4
2
0
10
C‐8
Fatty acid
9
C‐10
C‐12
8
7
C‐14
6
C‐16
C‐18
2 x C‐18
2 C 18
2
Polyricinoleate
5
4
3
g
y
Degree
of Polymerization
HLB-Value
•
•
•
•
•
non‐ionic O/W Emulsifier for oil gels
non‐
vegetable origin
HLB: 11.5 (calculated)
use level: 5 ‐ 10 %
use level: 5 ‐
use level: 5 10 %
oil phase: >75%
Phase Ingredient INCI
Supplier
%
A
Deionized Water
B
Glycerin
Various
15,00
Polyglyceryl‐5 Oleate
Dr. Straetmans
6,00
Caprylic/Capric Triglycerides
Various
31,50
Olea Europaea (Olive) Fruit Oil
Various
45,87
Tocopherol, Helianthus Annuus (Sunflower) Seed Oil
Dr. Straetmans
0,20
C
Formula #
q.s.
L004‐01‐11‐707
100,00
• Oil Gel properties:
– clear yellow viscous gel
– viscosity: ~ 60,000 cps
– stability: > 3 months @ stability: > 3 months @ 20 & 4
20 & 4°°C,
some turbidity at 40°
some turbidity at 40°C after 6 weeks • Formulating Tips:
Formulating Tips:
– Combine Polyglyceryl
Combine Polyglyceryl‐‐5 Oleate with Glycerin
– Add oil in small portions under virgorous stirring Add oil in small portions under virgorous stirring
to form homogenious gel, viscosity will increase
– Add increasingly larger portions of oil, form gel Add increasingly larger portions of oil form gel
before each seperate addition step
– Add water in the end to adjust the refractive index
Add water in the end to adjust the refractive index
– Remove air by vacuum
• Potential applications:
– cleansing gels
– massage gels
– self
self‐‐emulsifying bath gels
– exfoliating gels
– lip treatment gels
p
g
20
18
Polyglyceryl 10 Laurate
Polyglyceryl‐10
Laurate
(Solubilizer)
16
14
12
10
8
6
4
2
0
10
C‐8
Fatty acid
9
C‐10
C‐12
8
7
C‐14
6
C‐16
C‐18
2 x C‐18
2 C 18
2
Polyricinoleate
5
4
3
g
y
Degree
of Polymerization
HLB-Value
•
•
•
•
non ionic surfactant
vegetable based
HLB approximately
HLB:
i t l 15
use level: 3:1 (solubilizer : oil)
Transparency Test
Transparency Test
Water
98.8 %
88.8 %
78.8 %
Polyglycery‐10 Laurate
1.0 %
1.0 %
1.0 %
Fragrance
0.2 %
0.2 %
0.2 %
Ethanol
0.0 %
10.0 %
20.0 %
clear solubilisation up to 1 % essential oil
Phase
Ingredient INCI
A
Deionized Water
B
B1
Supplier
%
67,65
Glycerin
Various
7,00
Sodium Phytate
Dr.Straetmans
0,10
Ethanol
Various
20,00
Glyceryl Caprylate
Dr.Straetmans
1,00
Bisabolol
Kinetik
0,05
Polyglyceryl‐10 Laurate
Dr.Straetmans
2,00
Fragrance (Natural)
Various
0,20
Formula #
L010‐03‐107
100,00
• Toner properties:
– clear light yellow liquid
– pH: ~ 5.5
– stability: > 3 months @ stability: > 3 months @ 20 & 4
20 & 4°°C
• Formulating Tip:
– Combine fragrance oils directly into Polyglyceryl‐‐10 Laurate
Polyglyceryl
‐ Without Without parabens
parabens
‐ Without preservatives
ih
i
‐ Natural Background: ‐ Parabens have been found Parabens have been found in
in
breast cancer cells
breast cancer breast cancer cells
(Darbre, J. et al (Darbre, J. et al Appl. Toxicology, 24, Appl. Toxicology, 24, (2004),1.)
(2004) 1.))
(2004),1
‐ Parabens might Parabens might facilitate facilitate skin ageing
(Ishiwatari et al, Proc. IFSCC
(Ishiwatari et al, Proc. IFSCC
Conf. (2005
Conf
. (2005), 129
), 129‐‐135.)
‐ Without Without parabens
parabens
‐ Without preservatives
ih
i
‐ Natural Background::
Background
The consumer relates preservatives to negative effects to negative effects like:
like:
skin irritation
skin irritation
allergic reactions
cancer causing, etc.
cancer causing, etc.
‐ Without Without parabens
parabens
Background::
Background
‐ Without preservatives
ih
i
‐
iis considered by
is considered by
id d b
the consumer to be the opposite of opposite of chemical
chemical
‐
is associated by the is associated by the consumer with the attributes
consumer with the attributes
lik safe
like safe
like f and and gentle
d gentle
tl
organic acids
surface active materials
surface active materials
Product
Recommended
Performance against
Dosage [%]
pH range
gram+
gram‐
Yeast
Mold
Levulinic Acid
li i
id
0 5 1.0
0.5 –
10
<55
< 5.5




Anisic Acid
0.05 – 0.5
< 5.5




A
Access to levulinic acid from sustainable starting material
l li i
id f
i bl
i
i l
Mineral Acid
Vegetable Starch
Levulinic Acid
Acid
Levulinic Acid
pK‐
value
Amount of free acid at pH
4.5
5.0
5.5
6.0
4.64
58.0%
30.4%
12.1%
4.2%
‐ Levulinic acid has an infinite water solubility
Challenge test: 0.3 % levulinic acid in water
Challenge test: 0.3 Challenge test: 0.3 % levulinic acid in water
% levulinic acid in water
1000000
100000
10000
1000
100
10
Asp. Ni ger
Cand. Al bi c.
E.Col i
Pseud. Aer ugi n.
1
0
7
14
Staph. Aur eus
21
28
‐ Levulinic acid has broad antibacterial efficacy
organic acids it shows g
it shows no weakness no weakness against Pseudomonas
against Pseudomonas
g
‐ Unlike other Unlike other organic acids Ch
Characteristics
i i
Appearance
Clear, colourless liquid
Odour
mild, typical
INCI
Sodium Levulinate or Fragrance
Optimal pH
4.5 4.5 –– 5.5
Recommended Concentration
0.5 0.5 –– 1.0 %
Regulary Status
Listed in EU, US, Japan
Application
Emulsions and rinse
Emulsions and rinse‐‐off products
O2 / /
H2O2 / NaOH
trans‐Anethol
Natural Anisic Acid
p‐anisic acid is accessible in > 99% purity in a patented process by ozonolysis of trans‐anethole which is readily available from star anise oil or basil oil
Challenge Test: Challenge
Challenge Test: 0.2
Test: 0.2% 0.2%
0.2
% anisic acid as a fungicidal component in a % anisic acid anisic acid as
as a fungicidal component in a a fungicidal component in a
O/W Emulsion pH = 5.25
O/W Emulsion pH = 5.25
1000000
10000
100
Asp. Niger
1
0
E Coli
E.Coli
7
14
St aph. Aureus
21
28
Characteristics
Appearance
White to slightly yellowish powder
INCI
p‐Anisic Acid or Fragrance
Recommended dosage
0.1 – 0.3%
pH ‐ optimum of activity
4.5 – 5.5
Regulatory Status
15/2003/EC
IFRA Code
Nitro musk
CMR ingredients
GMO‐status
Application
Registered in EU, US, Japan
no listed allergens
full compliance
no
no CMR Substances
non‐GMO
Emulsions and rinse‐off products at pH values < 5,5. • Organic
Organic acids should be added to the aqueous phase
acids should be added to the aqueous phase
• When using Anisic Acid, a pre‐
When using Anisic Acid, a pre‐solution with small amounts of sodium hydroxide is often recommended
• Levulinic Acid can be added to the aqueous phase or used to adjust the pH of the finished formulation
• The pH of the formulation should not exceed 5.5 in order to provide sufficient antimicrobial activity
• Specific incompatibilities of the acids with other natural raw materials have not been reported
Each organic acid dissociates in an aqueous medium
Each organic acid dissociates in an aqueous medium
O
O
+ Base
H 3C O
O
HA
H 3C O
+
H
H
Base+
B
O‐
A
‐
Bases can be: water, salts (e.g. citrate, lactate, hydroxide)
c ds a d base o a dy a c a d p depe de equ b u
Acids and base form a dynamic and pH‐dependent equilibrium
pH = pK + log cA‐ / cHA
pH = pK + log cA‐ / cHA
pH
Water Phase
O
H 3C O
O‐
pH = pK
O
H 3 CO
O
H
After dissociation only the unpolar acid can penetrate the membrane. The The energy consumption and continuously low pH lead to Within the cell the acid dissociates, disturbs the pH‐equilibrium in the The cell struggles to maintain the pH by pumping H+ into the medium with salt death
salt remains in the medium and is inactive.
remains
in
and isThis process consumes energy (ATP)
inactive
This
process consumes energy (ATP)
the
the death of the microorganism.
thethe
microorganism
plasma
plasma and inhibts enzyme activity.
concurrent
concurrent intake of Na
andofintake
inhibts
ofmedium
enzyme
Na+. activity
pH
Bacterium
O
Lipid membrane
H 3C O
OH
M di
Medium
Oil Phase
HH++
H+
H
+
+ +
HH
O
H3CO
O
H3CO
OH
O
O
OH
O
OH
OH
OH
O
H3CO
OH
O
H3CO
OH
H3CO
H3CO
O
OH
OH
O
H3CO
H3CO
O
OH
H3CO
O
OH
OH
O
H3CO
OH
O
OH
H3CO
OH H CO
3
O
OH
O
OH
H3CO
OH
O
O
OH
OH
O
OH
H3CO
OH
H3CO
O
O
H3CO
O
H3CO
OH
H3CO
H3CO
OH
OH
H3CO
H3CO
OH
O
OH
OH
OH
O
O
O
H3CO
O
H3CO
OH
O
H3CO
OH
OH
O
H3CO
O
H3CO
O
OH
OH
O
H3CO
H3CO
O
O
O
H3CO
OH
O
OH
O
H3CO
H3CO
O
H3CO
O
H3CO
H3CO
OH
O
H3CO
OH
H3CO
O
H3CO
OH
O
O
H3CO
H3CO
Na+
Na+ Na+
OH
OH
O
H3CO
H3CO
O
H3CO
OH
O
H3CO
OH
OH
OH
H3CO
H3CO
O
O
H3CO
H3CO
OH
H3CO
O
OH
O
OH
Summary:
Acids which are capable of penetrating the cell membrane of microorganisms affect the intracellular pH equilibirium and thereby the metabolism of the cell. In order to re
In order to re‐‐establish the physiological pH the cell actively pumps out H+
thereby burning cell fuel ATP. Continious efforts to maintain the pH
thereby burning cell fuel ATP. Continious efforts to maintain the pH‐‐level of the cytosol finally leads to an exhaustion of cellular energy reserves.
y
y
gy
A sufficient efficacy of an organic acid requires:
a)) A sufficient number of uncharged acid molecules, which is related A ffi i t
b
f
h
d id
l l
hi h i l t d
to the pH and the pK of the organic acid
g
b)) A sufficient total concentration of the organic acid
pH = pK + log cA‐ / cHA
Anisic acid: comparison of 0.06 Anisic acid: comparison of 0.06 % at pH % at pH 5.0 5.0 with with 0.5 0.5 % at pH % at pH 6.0
6.0
10000000
1000000
100000
10000
cfu
Asp. niger pH 5
Asp. niger pH 6
C. albic. pH 5
C. albic. pH 6
E.coli pH 5
1000
100
E.coli pH 6
10
Ps. aerugin. pH 5
Ps. aerugin. pH 6
1
0
Staph. aureus pH 5
7
14
days
Staph.
p aureus pH
p 6
21
28
• Levulinic Acid and Anisic Acid are two e u c cda d
sc cda et o
antimicrobially active natural organic acids
g
p
y
• These organic acids are accepted for use by several natural organizations including OASIS (USA), BDIH (Germany), Organic Soil Association (UK) and Ecocert (France)
(UK) d E
t (F
)
• The antimicrobial efficacy of these acids is complementary providing broad spectrum
complementary, providing broad spectrum protection • Limitation: formulation pH should be <5.5
Limitation: formulation pH should be <5 5*
OH
OH
HO
O
HO
O
O
O
Glyceryl Caprylate
O
HO
Glyceryl Caprate
the glyceryl monoesters
H
OH
N
HO
O
O
Capryloyl Glycine
Ethylhexylglycerin
Glyceryl Caprylate
Glyceryl Caprylate
Glyceryl Caprate
Glyceryl Caprate
Access to naturally derived glyceryl monoesters
Coconut or Palm Oil as a natural source of shorter chain fatty acids
y
Distillatio
Cocofatty acids n
Distilled Acids
Esterification
Coconut Oil
Coconut Oil
Hydrolysis
Glycerol
Glyceryl monoester
Product
Recommended
Performance against
Dosage [%]
pH range
gram+
gram‐
Yeast
Mold
Glyceryl Caprylate
l
l
l
0 3 1.0
0.3 –
10
45 7
4.5 ‐



/
Glyceryl Caprate
1.0 – 2.0
4.5 ‐ 7




Challenge Test: 0.7% Glyceryl Caprylate in a g
y y py
pH = 5.1
O/W Emulsion
/
1000000
100000
10000
1000
100
10
Asp. Niger
Cand. Albic.
E.Coli
Pseud. Aerugin.
1
0
7
14
Staph. Aureus
21
28
Glyceryl Caprylate has strong efficacy against bacteria and yeast but only limited activity against fungi
Characteristics
Glyceryl Caprylate
Glyceryl Caprate
Appearance
Waxy solid
Waxy solid
INCI
y y py
Glyceryl Caprylate
Glyceryl Caprate
y y p
Recommended dosage
0.3 – 1.0%
1.0 – 2.0%
Optimal pH
4.5 – 7.0
4.5 – 7.0
Regulatory Status
g
y
Registered in EU, US, Japan
g
, , p
Registered in EU, US, Japan
g
, , p
GMO‐status
non‐GMO
non‐GMO
Monoester content
> 88 %
> 88 %
Glyceryl Caprylate is a good basic component for alternative preservation
Glyceryl Caprate is a good deodorant active (gram+ bacteria)
The active compounds are not used up and remain active The high surface activity and incompatible size of the The active compounds are small amphiphilic molecules, imolecules destabilizes the membrane
in the formula.
th thlt f lh d l t bili b th li id b
that exchange membrane lipids.
Oil Phase
Cell
O
O
Water Phase
Water Phase
OH
OH
0 min
i
1 min
5 min
10
min
Lit.:
•Bergsson,
G., Arnfinnsson, J, Karlsson, S.M.,
Steingrimsson, Ó, Thormar, H.,
In Vitro Inactivation of Chlamydia trachomatis by Fatty
Acids and Monoglycerides,
gy
, Antimicrob. Agents
g
Chemother. 42 (1998) 2290-2294.
TIME
Treatment of f
negatively stained Chlamydia trachomatis with 1 mM of Glyceryl Caprate
M f Gl
lC
Surface active materials, like Glyceryl Caprylate, can penetrate the interphase between oil phase and water phase Oil Phase
Oil Phase
Water Phase
Water Phase
At elevated concentrations, the high surface activity of the anti‐
At elevated concentrations, the high surface activity of the anti‐
microbial surfactant may result in a destabilization of the emulsion
Oil Phase
Oil Phase
Water Phase
Water Phase
Using mixtures of non
U
Using mixtures of non‐
i
i
f
‐ionic and anionic emulsifiers can i i
d i i
l ifi
efficiently lead to a stabilization of the emulsion
A suitable systems A suitable systems is:
is:
Polyglyceryl‐‐3 Stearate
Polyglyceryl
3 Stearate
‐ Na+
Sodium Stearoyl Lactylate
Using ionic emulsifiers leads to an additional layer of organized water molecules at the interphase
water molecules at the interphase
Oil Phase
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Na+
‐
N +
Na
‐
‐
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
‐
Na+
Na+
Na+
Na+
Na+
‐
Water Phase
The organic acids are a good choice for alternative preservation without
The organic acids are a good choice for alternative preservation without any change of the characteristics of a given formula if pH is suitable. In some cases the performance in emulsions needs to be enhanced.
Antimicrobial surfactants can be formulated at a wider pH range but may have an impact on the viscosity or the stability of emulsions. The use of blends of non‐
blends of non
non‐ionic and anionic emulsifiers can improve the stability of ionic and anionic emulsifiers can improve the stability of
emulsion based products.
In rinse‐off products inactivation can sometimes be observed due to the
In rinse‐
f
formation of micelles.
ti
f i ll
The efficacy of some antimicrobial surfactants alone against fungi is The efficacy of some antimicrobial surfactants alone against fungi is limited limited and additional combinations should be explored
p
• aa synergy between the (Levulinic Acid, Anisic synergy between the (Levulinic Acid Anisic
Acid) organic acids and the surface active materials (Glyceryl Caprylate) has been
materials (Glyceryl Caprylate) has been discovered!!
• boosts antimicrobial performance
boosts antimicrobial performance
Phase
Ingredient
A
Deionized Water
B
C
INCI
Supplier
%
~ 74.10
Sodium Phytate
Dr.Straetmans
0.10
Glycerin
Various
3.00
Glyceryl Caprylate
Glyceryl Caprylate
Dr Straetmans
Dr.Straetmans
p‐Anisic Acid or Fragrance
Dr. Straetmans
Sodium Hydroxide (10% sol.)
Various
Xanthan Gum
Kelco
0.20
Glyceryl Stearate Citrate
Dr. Straetmans
3.50
Decyl Cocoate
Goldschmidt
3.00
Olea Europaea (Olive) Fruit Oil
Various
2.00
Squalane
Various
6 00
6.00
Cetearyl Alcohol
Various
2.00
Caprylic/Capric Triglyceride
Various
4.00
Tocopherol, Helianthus Annuus (Sunflower) Seed Oil
Dr. Straetmans
0.15
Citric acid (20% sol.)
Various
q.s.
Sodium Hydroxide (10% sol.)
Various
q.s.
Formula #
D002‐50ff
as
indicate
d
q.s.
100.00
European
European Pharmacopoeia Criteria
Pharmacopoeia Criteria
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
Asp .Nig e r
0
Cand .Alb ci .
7
E.Coli
14
Pse ud .Aeru gin .
21
Sta ph .Au re us
28
A
A
A
A
A
Standard
Standard O/W, pH = 5.3
Standard O/W, pH = O/W pH = 5.3
53
Levulinic Acid 0 7%
Levulinic Acid 0.7%
Levulinic Acid 0.7
7%
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
B
NF
B
B
A
Standard
Standard O/W, pH = 5.3
Standard O/W, pH = O/W pH = 5.3
53
Levulinic Acid 0 7%
Levulinic Acid 0.7% + Levulinic Acid 0.7
7% + Anisic Acid 0.2
% + Anisic Acid 0.2%
Anisic Acid 0 2%
2%
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
B
F
A
A
A
Standard
Standard O/W, pH = 5.3
Standard O/W, pH = O/W pH = 5.3
53
Glyceryl
Glyceryl Caprylate 0.7%
Glyceryl Caprylate 0.7
Caprylate 0 7%
7%
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
B
A
A
A
A
Standard
Standard O/W, pH = 5.3
Standard O/W, pH = O/W pH = 5.3
53
Glyceryl
Glyceryl Caprylate 0.7% + Glyceryl Caprylate 0.7
Caprylate 0 7%
7% + Anisic Acid 0.2
% + Anisic Acid 0.2%
Anisic Acid 0 2%
2%
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
A
A
A
A
A
Standard
Standard O/W, pH = 5.3
Standard O/W, pH = O/W pH = 5.3
53
Glyceryl
Glyceryl Caprylate 0.5% + Glyceryl Caprylate 0.5
Caprylate 0 5%
5% + Levulinic Acid 0.3
% + Levulinic Acid 0.3%
Levulinic Acid 0 3%
3%
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
B
A
A
A
A
Standard
Standard O/W, pH = 5.3
Standard O/W, pH = O/W pH = 5.3
53
Glyceryl
Glyceryl Caprylate 0.5% + Glyceryl Caprylate 0.5
Caprylate 0 5%
5% + Levulinic Acid 0.3%
% + Levulinic
Levulinic Acid 0.3%
Acid 0 3%
+ Anisic Acid 0.2
+ Anisic Acid 0.2%
%
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
A
A
A
A
A
• The antimicrobial efficacy of organic acids at h
b l ff
f
d
pH 5.3 could be increased significantly in combination with surface active antimicrobial bi i
ih f
i
i i bi l
materials like Glyceyrl Caprylate
• Can we use this synergy to extend the scope y gy
p
of the organic acids to high pH values?
O/W T t E l i
O/W Test Emulsion, pH 6,5 challenge tests
H 6 5 h ll
t t
1
Glyceryl Caprylate
2
3
0,3
0,7
Levulinic Acid
Levulinic Acid
07
0,7
07
0,7
Anisic Acid
0,4
0,4
0,4
pH‐value
6,5
6,5
6,5
Standard
Standard O/W, pH = 6.5
Standard O/W, pH = O/W pH = 6.5
65
Levulinic Acid 0.7% + L li i A id 0 7%
Levulinic Acid 0.7
7% + Anisic Acid 0.4
% A
Anisic Acid 0.4% i i A id 0 4%
4% %
1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
A
F
B
A
A
Standard
Standard O/W, pH = 6.5
Standard O/W, pH = O/W pH = 6.5
65
LLevulinic Acid 0.7
Levulinic Acid 0.7% li i A id 0 7%
7% + Anisic Acid 0.4
% + Anisic Acid 0.4% + A i i A id 0 4%
4% + %
Glyceryl Caprylate 0.3% Glyceryl Caprylate 0.3% 1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
A
A
A
A
A
Standard
Standard O/W, pH = 6.5
Standard O/W, pH = O/W pH = 6.5
65
Anisic Acid 0.4% + A i i A id 0 4%
Anisic Acid 0.4
4% + Glyceryl Caprylate 0.7
% Gl
Glyceryl Caprylate 0.7% lC
l
07
7%
%
% 1000000
100000
10000
1000
100
10
EP Criteria
1
Aspergillus Niger
Candida Albicans
Escherichia Coli
Pseudomonas Aeruginosa
St h l
Staphylococcus
Aureus
A
0
Asp e rg u
li sn g
i er
Can did a alb ci an s
7
Esc h erci hia c oli
14
Pse udo mo na saeru gin osa
21
Sta ph yo
l c o c c usau re u s
28
A
A
A
A
A
The surfactants cause a higher permeability by forming pores Surface active species penetrate the cell membrane and The acid molecules can penetrate more easily to unfold their in the membrane. d
destabilize the structure of the membrane activity within the cell. h b l hbh h
ll
f h
b
O
H 3C O
OH
O
O
OH
O
H3CO
OH
H3CO
O
H3CO
H3CO
O
H3CO
OH
OH
H3CO
OH
O
H3CO
O
OH
O
O
OH
OH
H3CO
O
OH
O
OH
H3CO
O
H3CO
H3CO
OH
H3CO
O
OH
O
OH
O
OH
H3CO
O
H3CO
OH
H3CO
H3CO
O
OH
OH
O
H3CO
H3CO
OH
O
OH
H3CO
O
OH
O
OH
Organic acids and surface active substances are versatile options for the alternative preservation of cosmetics.
Interesting synergistic effects are observed when organic acids and surface active substances are combined
d f
b
b d
By combining with surface active substances the scope of By combining with surface active substances the scope of application for organic acids can be extended to higher pH‐
application for organic acids can be extended to higher pH‐values application for organic acids can be extended to higher pH
values
(up to 6.5
(up to 6.5) ) Depending on the type of Depending
Depending on the type of formulation, the on the type of formulation, the amount of surface formulation the amount of surface amount of surface
active substances can be significantly lowered in synergistic combinations to avoid stability problems.