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To order reprints or e-prints of JDD articles please contact [email protected]
May 2012
633
Volume 11 • Issue 5
Copyright © 2012
ORIGINAL ARTICLES
Journal of Drugs in Dermatology
A Comparison of Physicochemical Properties
of a Selection of Modern Moisturizers:
Hydrophilic Index and pH
Vivian Y. Shi BS,a Khiem Tran PhD,b and Peter A. Lio MDc
University of Illinois, College of Medicine, Chicago, IL
University of Illinois College of Medicine, Department of Pharmacology, Chicago, IL
c
Northwestern University Feinberg School of Medicine, Department of Dermatology, Chicago, IL
a
b
ABSTRACT
Objective: To quantify and compare the physiochemical properties of various topical emollients and to correlate these findings with
the products’ potential to maintain the stratum corneum (SC) acid milieu, while possessing the appropriate water content for skin
rehydration, user adherence, and comfort.
Material and Methods: The pH and hydrophilic fraction of 31 skin moisturizers sold in the US were measured. Hydrophilic Index
(HI) was calculated using the “HI equation.” The two parameters were charted using a scatter plot with quadrant divisions. Products with lower hydrophilicity were considered “more greasy” and assigned a lower HI as compared to their counterparts with a
higher hydrophilicity.
Results: Our findings are in good accordance with common clinical impressions: lotions generally have higher HI, while ointments have
lower HI. The majority of the products tested fall into low HI, suggesting that a large percentage of the products may be rich in overall
lipid content. The pH values range widely, from 3.7 to 8.2, with the majority of the products close to the physiologic skin pH of 4 to 6.
Conclusion: This study introduces HI as a novel method of quantifying the aqueous content of topical emollients. When considered
together with pH, the two indices can guide providers in choosing the most suitable emollients for patients with skin diseases involving altered acid mantle and barrier disruption, such as atopic dermatitis, irritant contact dermatitis, and ichthyosis vulgaris.
J Drugs Dermatol. 2012;11(5):633-636.
INTRODUCTION
A
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vast array of choices are available for skin moisturizers,
making the selection process an overwhelming task for
both consumers and health care practitioners. Despite
this problem, few studies have compared the physicochemical
properties between various brands in an independent fashion.
The Acid Mantle
Healthy human skin lies in the pH range of 4 to 6.1-4 An increase
in stratum corneum (SC) pH can disrupt the activity of enzymes
involved in keratinization, barrier restoration, and anti-microbial function.5-6 This phenomenon is seen in atopic dermatitis7-9
and other xerotic skin diseases10-11 and correlates with disease
severity of dryness,9 pruritus,8 and total skin involvement.3,6,8
Chemicals applied to the skin are an important exogenous factor that may stabilize the skin’s acid mantle.3 Therefore, topical
products with near-physiologic pH are considered best in prevention and treatment of these same skin abnormalities.3
Formulations of Moisturizers
Topical products are traditionally divided into very limited
and general classes, namely ointment, cream, lotion, gel, and
foam.12 There have been many modern additions and changes
to these standard excipients. The “lotion” from one manufacturer may be significantly texturally more viscous than the
“cream” of another manufacturer. This system creates obvious confusion in selecting an emollient with the desirable
texture and reflects the need for a more precise and standardized classification. In an attempt to address this problem, we
introduce Hydrophilic Index (HI) as a novel methodology to
measure the aqueous component of a topical product, and utilize it as an indirect quantification of “greasiness.”
In this study, we assessed the pH and HI of 31 skin moisturizers
sold in the US, and then combined these two parameters to
determine which products have the most potential to restore
SC acid milieu and provide sufficient hydration, yet possess the
appropriate aqueous content to suit user preference.
METHODS AND MATERIALS
pH Measurement
A pea sized amount of moisturizer was placed on Parafilm®
wrap. pH was measured using a glass flat tip electrode (Hanna®
HI 99191) with accuracy: pH = ± 0.02 at 25°C. All measurements
were performed 5 times to achieve their standard deviations.
© 2012-Journal of Drugs in Dermatology. All Rights Reserved.
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May 2012 • Volume 11 • Issue 5
FIGURE 1. Separation of hydrophobic and hydrophilic layers after
centrifugation. The most translucent (aqueous) layer is extracted.
a) Motor Oil; b) Aquaphor® Ointment; c) Eucerin® Original Dry Skin
Therapy Cream; d) Eucerin® Original Dry Skin Therapy Lotion; e) Cetaphil® Restoraderm Skin Restoring Moisturizer; f) Aveeno® Advanced
Care Moisturizing Cream; g) Dove® Day Lotion (SPF15); h) CeraVe®
Moisturizing Cream; i) Neosalus® Cream.
V. Y. Shi, K. Tran, P. A. Lio
FIGURE 2. pH plotted against HI. The median values for pH (6.00) and
HI (50.00) were selected for quadrant division. Emollients are divided
into quadrants and arranged numerically within each quadrant according to their HI values. Refer to Table 1 for product names.
Hydrophilicity Measurement
To measure, we placed 0.25 g of each product and 750 microliters of
H2O into a 1.7 mL microcentrifuge tube, producing a total weight of
1.0 g (density of H2O = 1.0 g/cm3 = 1.0 g/ml). The tube was vortexed
at maximum speed for 30 seconds to allow adequate emulsification
of the two components. In our experience, a 1:3 product to water
ratio allows for optimal mixing. Next, the mixture was centrifuged
at 25°C for 15 minutes. This separated the denser, more hydrophilic
layer on the bottom from the lighter, more hydrophobic layer on
top (Figure 1). The most translucent layer was assumed to have the
most aqueous component and was extracted and weighed. This
weight was converted to volume assuming density of H2O = 1.0 g
per cm3 = 1.0 g per ml. The product with the highest hydrophilicity
will best emulsify with water, have the highest percentage of emulsified H2O, and least amount of water extracted. All HI measurements
were performed 5 times to achieve their standard deviations.
Interestingly, CeraVe® Moisturizing Cream, though clearly
“heavier” than CeraVe® Moisturizing Lotion when handled, was
found have an HI of 92, whereas the lotion only has an HI of
66. Such counterintuitive results may be due to delivery technologies, which may alter the perception of both hydrophobic
and hydrophilic components.13 This property may explain our
finding that centrifugation leads to its separation into multiple
layers, a finding also seen in Dove® Day Lotion (Figure 1). Neosalus® also defies easy categorization: though marketed as a
cream, it has the highest HI of all the products, and remains
completely emulsified despite centrifugation.
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Calculation of Hydrophilic Index—The HI Equation
HI = (1.0 g - weight of aqueous layer in grams) = % emulsified H2O
1.0 g x 100%
We selected Shell® motor oil and de-ionoized water as controls
for HI measurement due to their absolute respective hydrophobicity and hydrophilicity.
RESULTS
Among the 31 products studied, pH values ranged from 3.73
(Vanicream® Light Moisturizing Lotion) to 8.19 (Eucerin® Intensive Repair Body Lotion), with the majority falling within
physiologic skin pH of 4 to 6 (Table 1). The HI also exhibited a
wide range of values, from 26.84 (Triple Paste®) to 100.00 (Neosalus® Cream). Nearly 2/3 of the products fell below HI 50 (Table
1). This suggested that a large number of moisturizers are rich
in lipid content. Our findings are in agreement with the common
clinical impression: ointments such as Aquaphor® have an HI of
28, while the less greasy Cetaphil® Moisturizing Cream has an HI
of 44. The pH values were plotted against HI forming a scatter
plot (Figure 2) and were divided into four quadrants using arbitrary lines representing median values for the two indices.
DISCUSSION
The two primary goals of a moisturizer are to introduce water directly into the SC and to prevent transepidermal water loss (TEWL).
These two tasks are accomplished by the hydrophilic and hydrophobic components of a moisturizer, respectively.12,14-16 Increased
SC pH results in barrier dysfunction and decreased antimicrobial
capability, both of which play important roles in the pathogenesis
of skin diseases such as atopic dermatitis,7-9 irritant contact dermatitis,17-18 and ichthyosis vulgaris.10-11 Application of moisturizers
with appropriate pH and HI can potentially prevent and improve
these skin diseases. When choosing a suitable moisturizer for
such patients, providers could consider products in Quadrants I
and II because their low pHs may allow for better repair of the acid
mantle and antimicrobial defense capability. Additionally, dermatologists could recommend products with an HI that matches user
comfort and cosmetic tolerability, while considering how effective
they are at rehydrating and protecting the skin. More importantly,
however, if a patient does not like an aspect of a moisturizer (eg,
“It’s too greasy”), recommending another agent with a different
HI may provide a more suitable choice.
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TABLE 1.
Thirty-one Selected Emollients and Their Respective pH Values and Hydrophilic Indexes (HI)
#
Brand and Product Name
HI
pH
Quadrant I
1
CeraVe® moisturizing cream
92.29 ± 0.58
5.49 ± 0.02
2
Aquanil® lotion
74.52 ± 0.03
5.19 ± 0.04
3
Acid Mantle®
68.21 ± 7.40
4.71 ± 0.01
4
CeraVe® moisturizing lotion
66.27 ± 2.51
5.68 ± 0.02
5
Vaseline intensive rescue skin protectant body lotion
62.10 ± 1.62
4.30 ± 0.02
6
Aveeno® daily moisturizing lotion
54.34 ± 4.20
5.62 ± 0.01
7
CeraVe® facial moisturizing lotion PM
50.53 ± 4.66
5.95 ± 0.01
®
Quadrant II
8
Vanicream® light moisturizing lotion
48.58 ± 1.41
3.73 ± 0.03
9
Aveeno® skin relief moisturizing lotion with menthol
46.28 ± 1.39
5.46 ± 0.02
10
DML® forte body moisturizing cream
44.70 ± 3.92
5.94 ± 0.08
11
Cetaphil® moisturizing cream
45.24 ± 2.81
4.71 ± 0.02
12
Eucerin® calming cream
45.12 ± 4.42
5.41 ± 0.02
13
Eucerin® menthol itch relief lotion
44.37 ± 3.25
4.81 ± 0.03
14
Aveeno® positively radiant daily moisturizer
44.33 ± 1.50
5.54 ± 0.04
15
Aveeno skin relief moisturizing lotion
39.11 ± 2.30
4.88 ± 0.02
16
Cetaphil® restoraderm skin restoring moisturizer
38.42 ± 2.69
5.94 ± 0.02
17
Cetaphil® daily advance ultrahydrating lotion
32.35 ± 2.21
5.65 ± 0.01
18
Eucerin original dry skin therapy lotion
31.92 ± 1.18
5.97 ± 0.03
19
Epiceram®
31.48 ± 2.45
5.45 ± 0.01
20
Eucerin® intensive repair body cream
30.27 ± 2.19
5.98 ± 0.03
21
Vanicream® moisturizing skin cream
29.49 ± 0.94
4.27 ± 0.05
22
Theraplex® emollient for severely dry skin
28.43 ± 4.49
4.62 ± 0.18
®
®
Quadrant III
23
Neosalus® cream
24
Aquanil® HC
25
26
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100.00 ± 0.00
7.40 ± 0.10
67.63 ± 1.45
6.35 ± 0.12
Eucerin® intensive repair body lotion
59.14 ± 2.72
8.19 ± 0.03
Dove® day lotion
54.50 ± 1.57
6.47 ± 0.02
Quadrant IV
27
Aveeno® advanced care moisturizing cream
46.20 ± 0.82
6.35 ± 0.03
28
DML® moisturizing lotion
36.68 ± 2.15
6.55 ± 0.01
29
Aquaphor® ointment
27.98 ± 1.62
6.82 ± 0.20
30
Eucerin® original dry skin therapy cream
27.41 ± 1.17
8.01 ± 0.04
31
Triple Paste®
26.84 ± 0.69
6.60 ± 0.04
Within each quadrant, the emollients are listed from highest to lowest HI. pH and HI values were measured five times to achieve the standard deviation values shown.
Quadrant I products are hydrophilic, and can quickly hydrate upper layers of SC.19 These products may require more frequent
application because the extent of their moisturization relies on the
concentration of the product applied. Furthermore, most of their
water content is retained largely in the upper layers of the SC, and
does not benefit the lipid metabolism in the deeper SC.20 However,
their aqueous texture makes them easier to apply, and these may
be more cosmetically elegant and acceptable and therefore more
suitable for patients who cannot tolerate greasier products.
Quadrant II products are more hydrophobic, and can retain
water in both the upper and deeper SC. Upon application, a
fraction of the product is retained on the skin surface, which
can decrease water permeability by acting as a physical occlusant. They may also penetrate into deeper SC and change
the packing and lamellar organization of the intercellular lipid
matrix, further making it impermeable to water evaporation.19-22
Unfortunately, their texture may increase the risk of occlusive
folliculitis12 and may also diminish patient acceptance and
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compliance23 by leaving greasy stains on clothing or causing a
physical sensation of “greasiness.”
Products in Quadrants III and IV have a more alkaline pH and
therefore may be less desirable in restoring skin pH, but may
have other characteristics that supersede this single measure.
The Quadrant IV products may provide better hydration than
the more hydrophilic agents in Quadrant III.
HI provides an objective, in vitro assessment of the aqueous
content of the products, without reliance on human subjects or
perception, thus allowing straightforward and consistent measurements. Future studies should be done to correlate HI with
user perception of emollient texture and to assess how products
with different HI and pH may actually influence SC in TEWL and
corneometry, and perhaps even in disease outcome. Additionally, topical products and medications may be divided into more
precise vehicle categories with respect to both the HI and the pH,
and be selected to tailor user preference and clinical goals.
DISCLOSURES
Dr. Lio has served as an advisory board member for Aveeno,
Galderma, and Onset Therapeutics. Dr. Tran and Ms. Shi have no
conflicts of interest to declare.
REFERENCES
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Schmid-Wendtner MH, Korting HC. The pH of the skin surface
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Lambers H, Piessens S, Bloem A, Pronk H, Finkel P. Natural skin
surface pH is on average below 5, which is beneficial for its resident flora. Int J Cosmet Sci. 2006;28(5):359-370.
Elias PM. Stratum corneum defensive functions: an integrated
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Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu of the horny
layer: new findings on the physiology and pathophysiology of skin
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Sparavigna A, Setaro M, Gualandri V. Cutaneous pH in children affected by atopic dermatitis and in healthy children: a multicenter
study. Skin Res Technol. 1999;5(4):221-227.
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TEWL in eczematous and clinically uninvolved skin. Acta Derm
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Eberlein-Konig B, Schafer T, Huss-Marp J, et al. Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of
primary school children. Acta Derm Venereol. 2000;80(3):188-191.
10. Ohman H, Vahlquist A. The pH gradient over the stratum corneum
differs in X-linked recessive and autosomal dominant ichthyosis:
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11. Menon GK, Ghadially R, Williams ML, Elias PM. Lamellar bodies
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and abnormal desquamation. Br J Dermatol. 1992;126(4):337-345.
12. Lynde CW. Moisturizers: what they are and how they work. Skin
Therapy Lett. 2001;6(13):3-5.
13. Bikowski J, Shroot B. Multivesicular emulsion: a novel, controlled-release delivery system for topical dermatological agents.
J Drugs Dermatol. 2006;5(10):942-946.
14. Anderson PC, Dinulos JG. Are the new moisturizers more effective? Curr Opin Pediatr. 2009;21(4):486-490.
15. Draelos ZD. Active agents in common skin care products. Plast
Reconstr Surg. 2010;125(2):719-724.
16. Kraft JN, Lynde CW. Moisturizers: what they are and a practical
approach to product selection. Skin Therapy Lett. 2005;10(5):1-8.
17. Wilhelm KP, Maibach HI. Susceptibility to irritant dermatitis induced by sodium lauryl sulfate. J Am Acad Dermatol.
1990;23(1):122-124.
18. Gfatter R, Hackl P, Braun F. Effects of soap and detergents on skin
surface pH, stratum corneum hydration and fat content in infants.
Dermatol. 1997;195(3):258-262.
19. Caussin J, Groenink HW, de Graaff AM, et al. Lipophilic and hydrophilic
moisturizers show different actions on human skin as revealed by cryo
scanning electron microscopy. Exp Dermatol. 2007;16(11):891-898.
20. Caussin J, Rozema E, Gooris GS, Wiechers JW, Pavel S, Bouwstra JA. Hydrophilic and lipophilic moisturizers have similar penetration profiles but different effects on SC water distribution in
vivo. Exp Dermatol. 2009;18(11):954-961.
21. Caussin J, Gooris GS, Bouwstra JA. FTIR studies show lipophilic moisturizers to interact with stratum corneum lipids, rendering the more
densely packed. Biochim Biophys Acta. 2008;1778(6):1517-1524.
22. Caussin J, Gooris GS, Groenink HW, Wiechers JW, Bouwstra JA. Interaction of lipophilic moisturizers on stratum corneum lipid domains
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23. Loden M. Role of topical emollients and moisturizers in the
treatment of dry skin barrier disorders. Am J Clin Dermatol.
2003;4(11):771-788.
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ADDRESS FOR CORRESPONDENCE
Peter A. Lio MD
1455 N. Milwaukee Ave, 2nd Floor
Chicago, IL 60622
Phone:…..................................................................(773) 276-1100
E-mail:........................................................p-lio@northwestern.edu
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