Formulating Cleansers for Sensitive Skin:creating a skin compatible cleanser
Russel [email protected]
TeamWorks, Chicago, IL
31 March 2010
Sensitive Skin Cleanser brief
Design a skin cleanser that is….
1) Non-irritating
2) Ideal for sensitive skin
3) Smells great
4) High foaming
5) Clear
6) Preservative free
7) “Cures Eczema”
XYZsensitive
skin facial cleanser
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 of a current facial skin 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
XYZfacial
cleanser
XYZsensitive
skin facial cleanser
Skin & skin lipidsCeramides Cholesterol Surfactant Fatty acid
Bouwstra et al J Lipid Res. 42, 1759 (2001)
EM
Jiang et al, J Derm Sci, 32, 243 (2003)
Gonneke, Bouwstra et al Soc Invest Derm, 117, 710 (2001)
X-ray scattering
Domain mosaic model, SC lipid organization (Forslind, 1994, Acta Derm Venereo)
• 3 lipid phases (orthorhombic, hexagonal, disordered or liquid)
Crystalline domainsDisordered regions
X-ray diffraction
Study of skin lipids
Cleanser(Surfactant monomers & micelles)
Skin(Surface layers)
Inflammation Oxidative Stress
Cell Signaling
2) Remain in skin and alter/ disrupt skin structure
Surfactants, cleansers, interact with skin
1) RemoveBarrier Components (lipids, NMF, cerimides, enzymes)
ImpairedBarrier
Redness Dryness, Itchy
SensorialIrritation
Uncomfortable
www.themomsbuzz.com/moms_buzz/health/index.html
Surfactant have many effects on skin
• lipid removal
• NMF removal
• enzyme disruption
• protein denaturation
• lipid disorganizations
• penetrate into skin
• membrane disruption
• 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 penetration into SC: IR, Raman
Size of micelles –light scattering
Thermodynamics of micelle disassociation -μcalorimetry
Surfactant dynamicsPendant drop
micelle surface chargeZeta potential
Sensitive Skin Cleanser briefDesign a skin cleanser that is….
1) Non-irritating
2) Ideal for sensitive skin
3) Smells great
4) High foaming
5) Clear
6) Preservative free
7) “Cures Eczema”
XYZsensitive
skin facial cleanser
target
R. Walters, M. Fevola, Cosm. & Tol. 123 (2008) 53-60.
A cleanser for sensitive skin cannot be all things
“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).
High CMC surfactant
Micelle
Low CMC surfactantMonomer
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 irritation3) Irritation = f(concentration)
“…mixed micelles of [surfactant] mixtures reduce the concentration of the irritating monomeric surfactant species.” Surfactants: Strategic Personal Care Ingredients, 2005
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)
Patent US6468614
2) Irritation = f(concentration > CMC) 3) No correlation between CMC &
surfactant aggressiveness
?
4) Time dependence
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Cleanser Concentration (% formula)
Dye
Lea
kage
(a.u
.)adult shampoo
adult body wash
baby cleanser
Transepithelial Permeation (TEP), surfactant aggressiveness
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.
• EC50: % concentration of formula at which 50% of maximum dye leakage occurs
• Mildness increases with increasing EC50
Diluted formula and fluorescein dye are applied to MDCK cell monolayer 15 min
epithelial monolayer
Dye leakage quantified via UV absorbance
0.0
0.2
0.4
0.6
0.8
1.0
1.2
0.1 1 10 100Concentration (% formula)
Dye
leak
age
(a.u
.)
EC50
Idealized TEP data
R. Walters, M. Fevola, J. LiBrizzi, K. Martin, Cosmetics and Toiletries (2008)
It is not just monomer… micelles size is important
Micelle size (nm) 3 4 6
Mildness (TEP) 0.1 0.5 3.5
Foam (ml): 820 720 350
Adult Body Face / Baby
Milder – more tissue compatible
Micelle size and mildness
Average Micelle (nm)
TEP Score (%) Mildness
Adult Shampoo 3.7 0.76
Baby Shampoo 7.1 3.89
0.0
0.1
0.2
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0 2 4 6 8 10 12 14
Frac
tion
of m
icel
les
Hydrodynamic Diameter, dH (nm)
PANTENE
JBS Surfactant micelles can penetrate through aqueous pores in the stratum corneum…
pore size of SC = 2.0 – 5.6nm
By making lager micelles, cleanser are more mild…
Adult ShampooMild baby/face cleanser
Dynamic light scattering
Moore, Blankschtien, J Cosmet. Sci. 54 29 (2003)
Blends of traditional surfactant systems
SLS sodium lauryl sulfate
SLES sodium lauryl ethyl sulfate
CAPB Cocamidol propyl betaine
PEG-80 sorbitane Laurate
body wash
SLES, CAPB
adult shampoo
SLS
face / babySLES, CAPB, PEG-80SL
Blending larger & larger surfactants… to create larger more stable micelles
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)
D. Discher, F. Ahmed, Polymersomes, Annual Review of Biomedical Engineering, 8, 323 (2006)
PEGylation creates invisible “stealth vesicles”
PEO covered micelles
NMT’s micelle model Fevola, Walters
PEG-80 Sorbitan Laurate
Lipid Biophysics:PEG phospholipid interactions suggest , the PEG lays down on the phospholipid surface, covering the bilayer
also fits light scattering micelle size results
G. Wu, et al. Interaction between Lipid Monolayers and Poloxamer 188: An X-Ray Reflectivity and Diffraction Study, Biophys J. 5, 3159 (2005).
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
Goddard, E. D. In Principles of Polymer Science and Technology in Cosmetics and Personal Care; Eds. Marcel Dekker, Inc.: New York, 1999; pp 181-215.
Cabane, B. J. Phys. Chem 1977, 81 1639.Maltesh_somasundarian, J Coll. Interface Sci, 157, 14 1993.
PEO / SDS pearl necklace model
Moore, Blankschtien, J Cosmet. Sci. 54 29 (2003)
Micelle charge – Zeta potential
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)
SDS: anionic surfactants
high negative charge
SLES/CAPB: anionic/amphoteric surfactants
moderate negative charge
APG
high (-) charge pushes head groups apart, and creates smaller more dynamics micelles – more aggressive
Addition of glycerin
S. Ghosh, et al., “Visualization and quantification of skin barrier perturbation induced by surfactant-humectant systems using two-photon fluorescence microscopy”, J. Cos. Sci. 59 263 (2008)
1% SDS
1% SDS + 10% glycerine
S. Ghosh, et al.“Ranking of aqueous surfactant-humectant systems based on an analysis of in vitro and in vivo skin barrier perturbation measurements” J. Cosmet Sci. 2007;58(6):599
Two-photon microscopy (TPM)
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.
Why…proposed that glycerin blocks or closes the aqueous channels in the SC.
also, glycerin alters the aqueous phase, likely changing micelle properties.
Low Mw Hydrophobically-modified polymers (HMPs) to mitigate surfactant irritation
Hydrophobically-modified polymers (HMPs)…
Hydrophobic group
Hydrophilic polymer backbone
…added to surfactant based cleansers… Mammalian Tissue
HMP-Surfactant Complex Surfactant
Micelle
…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
10 100 1000 10000
Surfactant Concentration (mg/L)
Surfactant
HMP + Surfactant
20
30
40
50
60
70
1
Surf
ace
Tens
ion
(dyn
/cm
)
CMC CMCPΔCMC
CAC
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.
Wilhelmy plate tensiometry
ΔCMC and irritation reduction
Importance of ΔCMC:
• Measure of HMP surfactant binding efficiency
• Correlates to irritation mitigation and reduced surfactant penetration
LiBrizzi, J.; Protz, A.; Ganopolsky, I.; Walters, R. Methods of reducing irritation in personal care compositions. US 7,157,414, 2007.
Addition of hmp results in decreased surfacatnt aggressiveness
TEP, Surfactant aggressiveness
Surfactant Penetration into Skin, Clinical ModelStudy Population
Adults aged 21-50, with no history of skin condition, n=9-10 subjects/cellStudy 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 stripEvaluations
Surfactant concentration, via colorimetric detection on each tapeTotal protein concentration on each tape
(μg
surfa
ctan
t / μ
g pr
otei
n)
~depth into skin; (# of tapes; 1 = skin surface)
0
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1 2 3 4 5 6 7 8 9 10
6% TDES
6% TDES + 1.8% hm-polymer
Control
Inflammatory Response (in vitro):Surfactant w/ and w/o hmp
PlaceboTDES/CAPB TDES/CAPB/
hm-polymer
43% reduction vs placebo
** p < 0.05 vs Placebo Control
**
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
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
Michael J. Fevola Joseph J. LiBrizzi
Neena TierneyKatharine Martin
Lisa GandolfiHuda Jerri
Aaron Nelson
Rutgers UniversityRichard Mendelsohn
Carol FlachGuangru Mao