Formulating Cleansers for Sensitive Skin:

creating a skin compatible cleanser

Russel Walters
rwalter2@its.jnj.com

TeamWorks, Chicago, IL
31 March 2010
Sensitive Skin Cleanser brief

Design a skin cleanser that is.

1) Non-irritating
XYZ
2) Ideal for sensitive skin sensitive
skin facial
3) Smells great cleanser

4) High foaming
5) Clear
6) Preservative free
7) Cures Eczema
Cleansing for Sensitive Skin
What is sensitive skin?

www.Drugstore.com : Sensitive skin = 265 products

Sensitive skin is many things

Dermatitis, atopic dermatitis (eczema), rosacea, psoriasis,
ichthyosis, seborrhea, contact dermatitis, surfactant-induced, poison
ivy, xerosis, acne, diaper rash,

inflammation of the skin with many causes: allergenic response,

contact with irritants, retinol, many others

reduced skin barrier: compromised skin or thinner skin:

Aging skin & infant & toddler skin

involves some kind of impaired barrier, burning and stinging, swollen red
itchy skin

Skin that requires less aggressive, milder cleansing

Formulation Strategies for sensitive skin

1) Add sensitive skin to the label the XYZ XYZ

of a current facial skin cleanser facial sensitive
cleanser skin facial
cleanser

2) Product forms:
creamy non-foaming, ~non-cleansing

3) Create a well designed skin compatible cleansers

skin & surfactant interactions with skin
tradeoffs
other components to add: anti-inflammatory ingredients
and not to add: allergens, unnecessary ingredients
Skin & skin lipids
Ceramides Cholesterol Fatty acid Surfactant
 Study of skin lipids X-ray
scattering
X-ray
diffraction

Bouwstra et al J Lipid Res. 42, 1759 (2001)

Gonneke, Bouwstra et al Soc Invest Derm, 117, 710 (2001)

Domain mosaic model, SC lipid organization

(Forslind, 1994, Acta Derm Venereo) EM
Crystalline
Disorderedregions domains

3 lipid phases (orthorhombic,

hexagonal, disordered or liquid)

Jiang et al, J Derm Sci, 32, 243 (2003)

 Surfactants, cleansers, interact with skin

1) Remove
Cleanser Barrier Components (lipids,
(Surfactant NMF, cerimides, enzymes)
monomers
& micelles)
2) Remain in skin and alter/
disrupt skin structure
Skin
(Surface
layers)

Impaired Inflammation Oxidative Cell Signaling

Barrier Stress

Redness Dryness, Uncomfortable Sensorial

Itchy Irritation

www.themomsbuzz.com/moms_buzz
/health/index.html
Surfactant have many effects on skin

lipid removal lipid disorganizations

NMF removal penetrate into skin
enzyme disruption membrane disruption
protein denaturation inflammation

because surfactants can interact with skin in many ways there are
many properties of surfactant that are important in achieving a mild
skin cleanser.

there are dozens of measurement to asses cleanser mildness- all

measure some aspect of surfactant/skin compatibility hopefully.
Understanding of physical chemistry of
surfactant systems
Surfactant at Air / Water
@ equilibrium
Whilemy tensiometry

Surfactant dynamics
Pendant drop

Thermodynamics of
micelle disassociation -
calorimetry

micelle surface charge

Zeta potential

Size of micelles
light scattering

Surfactant penetration
into SC: IR, Raman
Sensitive Skin Cleanser brief
XYZ
Design a skin cleanser that is. sensitive
skin facial
1) Non-irritating cleanser

2) Ideal for sensitive skin

3) Smells great
4) High foaming
target
5) Clear
6) Preservative free
7) Cures Eczema

A cleanser for sensitive skin

cannot be all things
R. Walters, M. Fevola, Cosm. & Tol. 123 (2008) 53-60.
Monomer theory of surfactant-induced irritation:
Surfactant Monomer causes irritation. Micelles are too large to penetrate into tissue
Surfactant systems with low CMCs are less irritating; lower monomer concentration
Led to desire to decrease the CMC; Mixed surfactant systems (e.g. anionic + amphoteric).

mixed micelles of [surfactant] mixtures reduce the concentration of the irritating monomeric
surfactant species. Surfactants: Strategic Personal Care Ingredients, 2005

Starting point was usually SLS, adding a co-surfactant does reduce irritation
Monomer theory not the full story
1) High CMC surfactant are not necessarily irritating:
2) Surfactant systems CMC << conc. that causes irritation
3) Irritation = f(concentration)

Monomer
High CMC surfactant Low CMC surfactant

Micelle
Monomer theory: problems
1) Surfactant systems CMC << conc. that causes irritation
CMC ~ 0.1wt% surfactant, while concentration in contact with skin ~2 wt%
the vast majority of surfactant exist in micelle (a small fraction as monomer)

3) No correlation between CMC &

2) Irritation = f(concentration > CMC) surfactant aggressiveness

Patent US6468614
?

4) Time dependence
Transepithelial Permeation (TEP), surfactant aggressiveness

Diluted formula and

fluorescein dye are applied Dye leakage
to MDCK cell monolayer 15 min quantified via UV
epithelial monolayer absorbance

Idealized TEP data 0.7

1.2
Dye leakage (a.u.)

1.0 0.6

0.8
0.5

Dye Leakage (a.u.)

0.6

0.4 EC50 0.4

0.2 0.3
0.0
adult shampoo
0.1 1 10 100 0.2
adult body wash
Concentration (% formula)
0.1 baby cleanser
EC50: % concentration of formula at which 50% of
maximum dye leakage occurs 0.0
0.0 1.0 2.0 3.0 4.0 5.0
Mildness increases with increasing EC50
Cleanser Concentration (% formula)

Cottin, M.; Zanvit, A. Toxicology in Vitro 1997 11(4), 399-405.

Clothier, R. et al. Toxicology in Vitro 1999 13(4/5), 713-717. R. Walters, M. Fevola, J. LiBrizzi, K. Martin, Cosmetics and Toiletries (2008)
It is not just monomer
micelles size is important

Milder more tissue compatible

Adult Body Face / Baby

Micelle size (nm) 3 4 6

Mildness (TEP) 0.1 0.5 3.5
Foam (ml): 820 720 350
 Micelle size and mildness
Dynamic light scattering

Moore, Blankschtien, J Cosmet. Sci. 54 29 (2003)

0.3 PANTENE
Adult Shampoo
Mild baby/face
JBS Surfactant micelles can penetrate through
Fraction of micelles

cleanser
aqueous pores in the stratum corneum
0.2

pore size of SC = 2.0 5.6nm

0.1

By making lager micelles, cleanser are

more mild
0.0
0 2 4 6 8 10 12 14
Hydrodynamic Diameter, d H (nm)

Average TEP Score

Micelle (nm) (%) Mildness
Adult Shampoo 3.7 0.76

Baby Shampoo 7.1 3.89

 Blends of traditional surfactant systems
Blending larger & larger surfactants to create larger more stable micelles

adult shampoo
SLS

SLS
body wash sodium lauryl sulfate
SLES, CAPB SLES
sodium lauryl ethyl sulfate

face / baby CAPB

SLES, Cocamidol propyl betaine
CAPB,
PEG-80SL
PEG-80 sorbitane Laurate

R. Walters, M. Fevola, J. LiBrizzi, K. Martin. Designing Cleansers for the

Unique Needs of Baby Skin, Cosm. & Tol. 123 (2008) 53-60.
addition of hm-polymer;
new surfactant architecture
Anionic
(SLS)

Ethoxylated anionic
(SLES, TDES)

Amphoteric
(CAPB)

Non-ionic
(PEG-80 sorbitane Laurate)
PEO covered micelles

PEG-80 Sorbitan Laurate

Lipid Biophysics:
PEG phospholipid interactions suggest ,
the PEG lays down on the phospholipid
surface, covering the bilayer
G. Wu, et al. Interaction between Lipid Monolayers and Poloxamer 188: An
X-Ray Reflectivity and Diffraction Study, Biophys J. 5, 3159 (2005).

also fits light scattering micelle size results

PEGylation creates invisible stealth vesicles

NMTs micelle model

Fevola, Walters D. Discher, F. Ahmed, Polymersomes, Annual Review of Biomedical Engineering, 8, 323 (2006)
Minimizing surfactant irritation potential with polymers
Water-soluble polymers (e.g. PEO, PVP) proposed for irritation mitigation
Explained in context of monomer theory
When CAC < CMC, polymer-surfactant aggregation results in lower monomer
activity
Blankschtein et al.: PEO minimizes SDS micelle penetration
Roadblocks to commercialization: Efficiency & Cost

PEO / SDS pearl

necklace model

Moore, Blankschtien, J Cosmet. Sci. 54 29 (2003)

Goddard, E. D. In Principles of Polymer Science and Technology in Cosmetics Cabane, B. J. Phys. Chem 1977, 81 1639.
and Personal Care; Eds. Marcel Dekker, Inc.: New York, 1999; pp 181-215. Maltesh_somasundarian, J Coll. Interface Sci, 157, 14 1993.
Micelle charge Zeta potential

SDS:
anionic surfactants
high negative charge

SLES/CAPB:
anionic/amphoteric surfactants
moderate negative charge

APG

A Lips, Role of Surfactant Charge in Protein Denaturation and Surfactant-Induced Skin

Irritation, Surfactants in Personal Care Products and Decorative Cosmetics 177-187
CRC Press (2006)

high (-) charge pushes head groups apart, and creates

smaller more dynamics micelles more aggressive
 Two-photon microscopy (TPM)
Addition of glycerin 1% SDS

Addition of glycerin has been shown in

many models to improve cleanser
compatibility with skin.

This has long been known, glycerin was

added to soaps to create milder soap.
1% SDS +
10% glycerine
Why
proposed that glycerin blocks or closes the
aqueous channels in the SC.

also, glycerin alters the aqueous phase,

likely changing micelle properties.

S. Ghosh, et al.Ranking of aqueous surfactant-humectant systems S. Ghosh, et al., Visualization and quantification of skin barrier
based on an analysis of in vitro and in vivo skin barrier perturbation perturbation induced by surfactant-humectant systems using two-
measurements J. Cosmet Sci. 2007;58(6):599 photon fluorescence microscopy, J. Cos. Sci. 59 263 (2008)
 Low Mw Hydrophobically-modified polymers
(HMPs) to mitigate surfactant irritation

Hydrophobically-modified
polymers (HMPs) HMP-Surfactant
Complex
Surfactant
Micelle

added to surfactant
based cleansers Mammalian Tissue
Hydrophilic
Hydrophobic polymer backbone
group

bind surfactant to form HMP-surfactant

complexes. Excess surfactant forms micelles.

HMPs reduce surfactant penetration

Surface tensiometry and delta CMC

Idealized plot of surface tension vs. surfactant concentration

70
Surfactant
HMP + Surfactant
Wilhelmy plate tensiometry
Surface Tension (dyn/cm)

60

50

CAC
40

30

CMC CMCP
CMC
20
1 10 100 1000 10000
Surfactant Concentration (mg/L)

LiBrizzi, J.; Protz, A.; Ganopolsky, I.; Walters, R. US 7,157,414, 2007.

Goddard, E. D. In Principles of Polymer Science and Technology in Cosmetics and Personal Care; Goddard, E. D.; Gruber, J. V., Eds. Marcel
Dekker, Inc.: New York, 1999; pp 113-180.
CMC and irritation reduction

Importance of CMC:
Measure of HMP surfactant binding efficiency
Correlates to irritation mitigation and reduced
surfactant penetration

TEP, Surfactant aggressiveness

Addition of hmp results in decreased

surfacatnt aggressiveness

LiBrizzi, J.; Protz, A.; Ganopolsky, I.; Walters, R. Methods of reducing

irritation in personal care compositions. US 7,157,414, 2007.
Surfactant Penetration into Skin, Clinical Model
Study Population
Adults aged 21-50, with no history of skin condition, n=9-10 subjects/cell
Study Design
Expose volar forearms to diluted cleanser solution under occlusive patch for 4 hours; rinse/dry skin, take
10 consecutive tape strips
Quantify surfactant & total protein concentration on each individual tape strip
Evaluations
Surfactant concentration, via colorimetric detection on each tape
Total protein concentration on each tape

6% TDES

0.3 6% TDES + 1.8% hm-polymer

(g surfactant / g protein)

Control

0.2

0.1

0
1 2 3 4 5 6 7 8 9 10
~depth into skin; (# of tapes; 1 = skin surface)
 Inflammatory Response (in vitro):
Surfactant w/ and w/o hmp

43% reduction
vs placebo
In Vitro:
Skin cultures, Epiderm (Mattek) skin equivalence

**

Study Design
Exposure: 10% dilution for 1 hr, then rinses
Cytokine response measured after 24 hours
Inflammatory Mediators (IL-1a, IL-1ra)
6 independent wells for each cleanser
Placebo
TDES/CAPB TDES/CAPB/
hm-polymer

** p < 0.05 vs Placebo Control

Summary
New understanding of surfactant tissue penetration (i.e. micelle
penetration model) offers new insight for design of mild cleansers

Cleanser can be designed to suite sensitive skin consumers, but there are
limitations on fomrulation

HMPs can be used to effectively reduce free micelle concentration,

enabling milder more tissue compatible cleanser (reduced surfactant
penetration, reduced inflammation markets, etc.)

Acknowledgements:
Johnson & Johnson
Rutgers University
Michael J. Fevola
Richard Mendelsohn
Joseph J. LiBrizzi
Carol Flach
Neena Tierney
Guangru Mao
Katharine Martin
Lisa Gandolfi
Huda Jerri
Aaron Nelson