The Promise Land: Developing Lotions Creams that Deliver

Personal care product formulators have tough jobs. They must juggle the requirements of marketing, manufacturing and regulatory staff while designing consumer-friendly products that meet customers’ expectations the first time and every time they use them. A fundamental rule is also implicit in their work: create a product that consumers need and want to use, because it delivers on all the properties they have been led to expect. If formulators are crafting a sunscreen, it must protect the consumer. If they say their product is anti-aging, then the active ingredients have to be present…and active.

Complicating this issue, it seems like every week some new finding or study about consumer health is trumpeted. A seemingly endless stream of studies yields the latest insights into factors that affect people’s well-being, sometimes with contradictory conclusions.1 This is due, in part, to the various pathways by which substances may enter—and affect—the body.Most substances enter the body through food and drink. Perhaps surprisingly, the second largest quantity enters through the lungs. It takes a lot of oxygen to keep the metabolic fires burning! But also of substantial importance are the substances applied to, and sometimes entering through, the largest human organ, the skin (Figure 1).2 That is the focus of this article: how to create lotions and creams that deliver what formulators promise, where they promise, and when they promise. Not surprisingly, the discussion starts with the canvas: the human skin.

Fig 1: The Five Layers of the Epidermis

Understanding Skin
Skin is comprised of two main layers, held to the underlying tissue by the hypodermis, or subcutaneous fat layer, which also provides a measure of padding and insulation from temperature change. The inner layer of skin is the dermis, which includes blood vessels, nerve endings, hair follicles, and sweat and sebaceous glands; enmeshed in connective tissues that include elastin and collagen and that provide skin much of its mechanical strength. The outer layer is the epidermis, which has five main sublayers and is home to four main cell types: keratinocytes (the vast majority, for barrier formation), melanocytes (for pigment formation), Merkel cells (for sensory perception) and Langerhans cells (for immune response). As cells comprising the epidermis migrate to the surface, they become keratin-rich, change shape, and ultimately die; forming the outermost sublayer of the epidermis, the stratum corneum. The stratum corneum has a “brick and mortar” type structure in which the hydrophilic cell remnants, called corneocytes, are the bricks and complex, bilayer-rich lipids (mainly ceramides, fatty acids, and cholesterol) are the mortar.3 The stratum corneum gradually sloughs off (desquamates) over a period of several weeks, replaced by cells from beneath. It is the stratum corneum that provides a water-resistant, albeit water-swellable, barrier from microbes, polymers and many other substances to the layers below.


Preserve and Protect
What are some of the issues formulators must address when formulating lotion and cream (emulsion-based) skin care products? Products intended to protect skin from solar irradiance, toxic-substance absorption, and/or evaporative water loss function best when the product is uniformly distributed over the stratum corneum, remains within the confines of the stratum corneum and retains its chemical integrity for the duration of use.

Consider sunscreens as an example. Sunscreen product development and regulations originally focused primarily on providing protection from the burning (UVB) rays of the sun.4 This measure of protection is expressed as the sun (or, more accurately, sunburn) protection factor or SPF. The longer a person can stay in the sun without perceptible erythema (reddening of the skin), the higher the SPF of the applied product. Protected by a properly applied SPF15 sunscreen, a relatively fair-skinned person can be exposed to 15 times the UVB radiation than when unprotected before starting to turn red.

Sun protection eventually proved to be about more than preventing sunburns. By the 1980s, it was evident that skin must be shielded from not just UVB rays, but also from the aging (UVA) rays of the sun. Further, both UVA and UVB rays were confirmed to be associated with various forms of skin cancer. Hence, sunscreens in many parts of the world now deliver not just sunburn protection, but also a UVA protection factor (UVA-PF, or PFA) rating and/or UVA protection that is proportionate to the UVB protection that the product also provides.5 New sunscreen regulations were recently released by the US Food and Drug Administration.

Now that the protection requirements of the sunscreen product have been established, the next issue is effective delivery. A room-darkening window shade is most effective when it is placed against the frame of a window, covers the entire window, remains closed and in place, and does not fall apart for as long as the sun is shining. Likewise, the best protection of the skin from UV occurs when a sunscreen is uniformly distributed over the entire surface of the stratum corneum, remains in place and is stable for the duration of sun exposure.

Uniform distribution is achieved with an emulsion system that promotes both ready spreading and uniform deposition over the skin during application. The emulsion must not be so thick that it does not spread evenly, nor so thin that it pools in crevices and pores, leaving the remainder of the stratum corneum under-protected. Pooling can be prevented, even in very fluid emulsions, by incorporating yield-value additives such as xanthan gum and cellulose gum. The sunscreen is kept in place through the use of water-resistance-enhancing polymers, such as C30-38 olefin/isopropyl maleate/MA copolymer, octadecene/MA copolymer, and VP/ eicosene copolymer. Various procedures for testing the degree of water resistance have been published.6,7

Perhaps the most difficult task is enhancing the stability of photolabile sunscreen active ingredients such as avobenzone. One way to do so is by optimizing the polarity of the oil phase.8 This typically involves increasing the polarity of the oil phase by replacing commonly used, but not very polar sunscreen solvents, such as isopropyl myristate and C12-15 alkyl benzoate, with more polar solvents, such as butyloctyl salicylate, diisobutyl adipate and dimethyl capramide.

Even more effective in many instances is the incorporation of singlet- and/or triplet-state-quenching compounds9 that allow avobenzone to transfer its excited state energy very rapidly. A rapid return to the ground state reduces the likelihood that avobenzone will instead move to a less excited state by degrading. By returning to the ground state, it is once again ableto absorb UVA radiation. In most formulations, triplet-state quenchers such as octocrylene, polyester-8 and undecylcrylene dimethicone, can markedly improve avo- benzone photostability. In sunscreens containing both octinoxate and avobenzone, which are notoriously photolabile, the extremely rapid singlet-state quencher, ethylhexyl methoxycrylene, can provide a much-needed boost to photostability.

The right formula creates an elegant feel on skin.

Getting Under the Skin
Next, consider a lotion or cream that carries ingredients that must interact with living skin cells to provide the desired result. Examples include local anesthetics, such as benzocaine and pramoxine, which relieve itching and irritation from insect bites, and skin-whitening agents, including arbutin, kojic acid and hydroquinone, which reduce melanin content in the skin. However, some ingredients target more than skin cells. Topical antibiotics, such as bacitracin, neomycin and polymyxin b, are used to fight pathogenic bacteria; topical antifungals, such as ketoconazole, miconazole and tolnaftate, are used to reduce fungal growth; and benzoyl peroxide is used to eliminate bacteria associated with acne. All of these microorganisms are unwelcome guests when they establish colonies in the skin.

Regardless of the specific cells targeted, the intended results cannot be achieved if the functional ingredients remain on the surface of the stratum corneum. They must penetrate, in some cases, as far as the basal level of the epidermis, to reach their targets. In addition, they must arrive in concentrations and at rates sufficient to exert their desired physiologic effect.

How can this be achieved? There are two routes for products that are applied to intact skin: one, penetration via pores and their associated glands, which exude sebum or sweat that is destined for the surface of the stratum corneum, and/or two, penetration through the extracellular lipid matrix that holds the corneocytes together. Regardless of the route, achieving permeation may be easier said than done, especially when the molecular weight of the functional ingredient increases to more than approximately 500 daltons and/or if it is exceptionally polar. After all, the stratum corneum functions as a barrier, and does so quite efficiently when its integrity is intact. So, what’s the solution?

Two common approaches are the use of liposomes, in which functional ingredients are encased for transport,10 or penetration enhancers, which solubilize functional ingredients and disrupt the bilayers of the extracellular lipid matrix, resulting in their fluidization and/or extraction.11 Indeed, many suppliers provide their functional ingredients either encased in liposomes or solubilized in solutions containing penetration enhancers to assist the formulator with the development of efficacious products. Judicious selection of liposomal composition, or of penetration enhancers such as ethoxydiglycol12 or dimethyl isosorbide,13 ensures introduction of the functional ingredient without appreciable irritancy.


Keeping Products Stable
A formulator can develop an amazing product, but it is useless if it decomposes while sitting on a store shelf. Stability and aesthetics are the primary physical factors that come into play when preparing a product for retail.

Product stability assessments, especially for cosmetic products, often focus on the physical stability of the product through freeze-thaw cycling; during refrigerated, room- and elevated-temperature storage; and while under fluorescent lighting and in indirect sunlight. For products with active and/or functional ingredients, these assessments are not sufficient. Active ingredients must also be tested to affirm their stability during manufacture, in storage and in use.

Anti-aging products based on retinol are a good example. Retinol is both oxidatively and photochemically unstable. As a result, when formulating with retinol, the first step in stability evaluation is confirming that the retinol does not thermally or oxidatively degrade during the manufacturing process. The next step is verifying that the retinol remains stable under the various storage conditions that are anticipated for the product. The final step is ensuring its stability in use, which is very important since retinol is quite photolabile. Photostability can nonetheless be achieved by incorporating the singlet-state quencher, ethylhexyl methoxycrylene, in the oil phase with the retinol.14

While inferior aesthetics may prove acceptable for products designed to provide immediate relief from a painful malady, a product designed as part of a daily skin care regimen must have pleasant aesthetics during dispensing and application, after dry down and during cleansing to ensure continued consumer use.

Dispensing characteristics can be modified by the appropriate selection of emulsifiers. Liquid emulsifiers tend to yield flowable lotion consistencies, while solid emulsifiers tend to yield firmer cream consistencies. The addition of a small amount (<1%) of cetyl and/or stearyl alcohol can often be used to convert a lotion to a cream or a cream to a paste. When high levels of oils are required to achieve the desired product performance, an oily or greasy feel during application and/or a glossy appearance following application may result. These can be mitigated through the incorporation of impalpable spherical silica or aluminum starch octenylsuccinate. For an even more elegant feel—especially appropriate for facial skin care—silicone elastomers such as C30-45 alkyl cetearyl dimethicone crosspolymer, dimethicone/bis-isobutyl PPG-20 crosspolymer or polysilicone-11 may be utilized. Ready removability is usually not a problem for oil-in-water (O/W)-based lotions and creams. For water-in-oil (W/O) systems, including a mid-HLB emulsifier in the oil phase may be beneficial.


Summary
Developing lotions and creams that deliver what they promise, when they promise, is the art of personal care formulation. This article addresses some of the considerations that must be taken into account to ensure that lotion and cream products live up to their formulators’ claims. The technology that is driving our industry to new heights requires excellent science and knowledge. It is exciting to work in this dynamic field.

References
1. Dr. John Briffa. “Why the sun is good for you,” The Daily Mail. Accessed April 8, 2011. http://www.dailymail.co.uk/health/article-48192/Why-sun-good-you.html.
2. Wikipedia. Accessed April 8, 2011. http://en.wikipedia.org/wiki/File:Gray940.png.
3. Miranda A. Farage, Kenneth W. Miller, Howard I. Maibach, eds., Textbook of Aging Skin, (Berlin, Heidelberg: Springer-Verlag, 2010), chap. 7, page 58, figure 7.4. http:// books.google.com/books?id=9-ALWZhXomAC&pg=PA55&lpg=PA55&dq=intercorneocyte+lipids&source=bl&ots=t0zC7OSzH7&sig=VAsMj6cNVMCplIKtgfcGSGU2iZU&hl=en&ei=Ap6XTaC0N8uDtgfp0tmKDA&sa=X&oi=book_result&ct=result&resnum=10&ved=0CFYQ6AEwCQ#v=onepage&q=intercorneocyte%20lipids&f=false
4. Sunscreen Drug Products for Over-the-Counter Human Use: Establishment of a Monograph; Notice of Proposed Rulemaking, Proposed Rules, 43(166) FR 38206-69, Aug. 25, 1978. (http://www.fda.gov/downloads/ Drugs/ DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs /StatusofOTCRulemakings/ucm090127.pdf)
5. European Commission Consumer Affairs website, last modified Oct. 13, 2010, http://ec.europa.eu/consumers/sectors/cosmetics/cosmetic-products/sunscreen-products/ index_en.htm.
6. 21 CFR 352 Sunscreen Drug Products for Over-the-Counter Human Use, Code of Federal Regulations. Revised as of April 1, 2010. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=352&showFR=1 (§ 352.76) or
http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm090244.pdf (§ 352.76)
7. COLIPA Guidelines: Guidelines for Evaluating Sun Product Water Resistance, December 2005. http://www.colipa.eu/publications-colipa-the-european-cosmetic-cosmetics-association/ guidelines.html?view=item&id=18.
8. Bonda, 2002. Methods of making and selling a sunscreen composition. US Patent 6,770,270, filed March 25, 2002, and issued Aug. 3, 2004.
9. Craig Bonda, “Sunscreen Photostability 101,” Happi, October 2009. http://www.happi. com/articles/2009/10/sunscreen-photostability-101.
10. Liposomes. Centerchem, Inc. [brochure]. Accessed April 8. 2011. http://www.centerchem.com/PDFs/Liposomes%208Es.pdf
11. Pankaj Karande et al. “Design principles of chemical penetration enhancers for transdermal drug delivery.” Proceedings of the National Academy of Sciences of the United States of America. March 2005. http://www.pnas.org/content/102/13/4688.full.
12. Innovadex website. Accessed April 8, 2011. http://www.innovadex.com/documents/1026726.pdf?bs=832&b=33781&st=20.
13. Super Refined Arlasolve DMI. Croda Health Care [brochure]. Accessed April 8, 2011. www.crodalubricants.com/download.aspx?s=133&m=doc&id=240.
14. Craig Bonda and Jean Zhang, “Photostabilization of Retinol and Retinyl Palmitate by Ethylhexyl Methoxycrylene,” Cosmetics & Toiletries, January 2011. http://www.cosmeticsandtoiletries.com/formulating/ingredient/aids/112819234.html


About the Author
Gary A. Neudahl, product application manager, The Hallstar Company, has spent 30 years in the personal care industry, developing hair care, skin care, sun care, color cosmetics, and toiletries formulations, having brought many finished products through scale-up to full production.He has been a member of the Society of Cosmetic Chemists since 1990 and has made presentations at meetings around the country.More info: gneudahl@hallstar.com