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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 aUniversity of Illinois, College of Medicine, Chicago, IL

bUniversity of Illinois College of Medicine, Department of Pharmacology, Chicago, IL cNorthwestern University Feinberg School of Medicine, Department of Dermatology, Chicago, IL

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. Prod-ucts 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 involv-ing altered acid mantle and barrier disruption, such as atopic dermatitis, irritant contact dermatitis, and ichthyosis vulgaris.

J Drugs Dermatol. 2012;11(5):633-636.

ABSTRACT

INTRODUCTION

A 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 MantleHealthy 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-microbi-al 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 fac-tor that may stabilize the skin’s acid mantle.3 Therefore, topical products with near-physiologic pH are considered best in pre-vention and treatment of these same skin abnormalities.3

Formulations of MoisturizersTopical 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 manufac-turer may be significantly texturally more viscous than the “cream” of another manufacturer. This system creates ob-vious confusion in selecting an emollient with the desirable texture and reflects the need for a more precise and standard-ized 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 uti-lize 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 MATERIALSpH MeasurementA 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.

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Journal of Drugs In Dermatology

may 2012 • Volume 11 • Issue 5 V. Y. Shi, K. Tran, P. A. Lio

Hydrophilicity MeasurementTo 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 emulsi-fied H2O, and least amount of water extracted. All HI measurements were performed 5 times to achieve their standard deviations.

Calculation of Hydrophilic Index—The HI EquationHI = (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 hydropho-bicity and hydrophilicity.

RESULTSAmong the 31 products studied, pH values ranged from 3.73 (Vanicream® Light Moisturizing Lotion) to 8.19 (Eucerin® In-tensive 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 (Neo-salus® 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 arbi-trary lines representing median values for the two indices.

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 tech-nologies, 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). Neo-salus® also defies easy categorization: though marketed as a cream, it has the highest HI of all the products, and remains completely emulsified despite centrifugation.

DISCUSSIONThe two primary goals of a moisturizer are to introduce water di-rectly into the SC and to prevent transepidermal water loss (TEWL). These two tasks are accomplished by the hydrophilic and hydro-phobic 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 der-matitis,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, derma-tologists 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.

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) Ceta-phil® Restoraderm Skin Restoring Moisturizer; f) Aveeno® Advanced Care Moisturizing Cream; g) Dove® Day Lotion (SPF15); h) CeraVe® Moisturizing Cream; i) Neosalus® Cream.

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 ac-cording to their HI values. Refer to Table 1 for product names.



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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 oc-clusant. 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

Quadrant I products are hydrophilic, and can quickly hydrate up-per 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.

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 100.00 ± 0.00 7.40 ± 0.10

24 Aquanil® HC 67.63 ± 1.45 6.35 ± 0.12

25 Eucerin® intensive repair body lotion 59.14 ± 2.72 8.19 ± 0.03

26 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.



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10. Ohman H, Vahlquist A. The pH gradient over the stratum corneum differs in X-linked recessive and autosomal dominant ichthyosis: a clue to the molecular origin of the "acid skin mantle"? J Invest Dermatol. 1998;111(4):674-677.

11. Menon GK, Ghadially R, Williams ML, Elias PM. Lamellar bodies as delivery systems of hydrolytic enzymes: implications for normal 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, con-trolled-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 effec-tive? 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 dermati-tis 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, Bouw-stra JA. Hydrophilic and lipophilic moisturizers have similar pen-etration 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 mois-turizers 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. In-teraction of lipophilic moisturizers on stratum corneum lipid domains in vitro and in vivo. Skin Pharmacol Physiol. 2007;20(4):175-186.

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.

ADDRESS FOR CORRESPONDENCE

Peter A. Lio MD1455 N. Milwaukee Ave, 2nd FloorChicago, IL 60622Phone:…..................................................................(773) 276-1100E-mail:........................................................p-lio@northwestern.edu

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 mea-surements. 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. Addition-ally, 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.

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4. Lambers H, Piessens S, Bloem A, Pronk H, Finkel P. Natural skin surface pH is on average below 5, which is beneficial for its resi-dent flora. Int J Cosmet Sci. 2006;28(5):359-370.

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6. Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu of the horny layer: new findings on the physiology and pathophysiology of skin pH. Am J Clin Dermatol. 2002;3(4):261-272.

7. Sparavigna A, Setaro M, Gualandri V. Cutaneous pH in children af-fected by atopic dermatitis and in healthy children: a multicenter study. Skin Res Technol. 1999;5(4):221-227.

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9. Eberlein-Konig B, Schafer T, Huss-Marp J, et al. Skin surface pH, stra-tum corneum hydration, trans-epidermal water loss and skin rough-ness related to atopic eczema and skin dryness in a population of primary school children. Acta Derm Venereol. 2000;80(3):188-191.



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