¹Scientific Insights Consulting Group Inc., Mississauga, ON, Canada
²Sunnybrook Health Sciences Centre, Toronto, ON, Canada
³University of Toronto, Toronto, ON, Canada

Conflict of interest:
Bonnie Kuehl has consulted for and accepted consulting fees from Aralez Pharmaceuticals and LEO Pharma Canada; Neil Shear has been a consultant/speaker for AbbVie, Celgene, Valeant, Lilly, Novartis, Janssen, LEO Pharma, and Sanofi Genzyme.

Abstract
Most people with mild-to-moderate psoriasis manage their disease with topical therapies. However, adherence to topical treatment remains a challenge, as the daily application creates a significant treatment burden. New topical therapeutic options need to offer higher efficacy and better patient acceptability, including easier application, to reduce treatment burden and enhance patient adherence. Topical foam vehicles are innovative alternatives to creams and ointments, addressing many patient challenges with traditional vehicles. Well-designed foam vehicles are easily spread over large areas of the skin, while importantly not leaving a greasy or oily film on the skin after application. Calcipotriol/betamethasone dipropionate aerosol foam is a new psoriasis treatment option that is rapidly effective, offers greater efficacy versus ointment and gel formulations, and has been shown to increase patient treatment satisfaction. Hence, by addressing the several crucial unmet clinical needs in patients with mild-to-moderate psoriasis, this optimized foam formulation is poised to improve treatment follow-through.

Key Words:
calcipotriol/betamethasone dipropionate, drug delivery, vehicle, aerosol, foam, psoriasis, topical

Introduction

Psoriasis is an immune disorder that most commonly manifests itself with visible plaques on the skin, resulting in considerable morbidity for those affected. The World Health Organization characterizes psoriasis as “a chronic, non-communicable, painful, disfiguring and disabling disease for which there is no cure.”¹ The majority of patients are classified as having mild-moderate disease with an estimated 20% having moderate-severe disease.² In a multinational survey (US, Canada, France, Germany, Italy, Spain, UK), dermatologists acknowledged that psoriasis is undertreated with an ongoing unmet treatment need for patients.³ In the survey, dermatologists reported not initiating or maintaining treatment due to concerns regarding the long-term safety, tolerability and efficacy of currently available therapies.³ The MAPP survey (population-based survey of psoriasis and/or psoriatic arthritis patients in North America and Europe) revealed that the majority of psoriasis patients are undertreated; >80% of patients with ≥4 palms body surface area (BSA) were receiving no treatment or topical treatment only. Further, 57% who received oral therapy and 45% who received biologic therapy discontinued treatment, citing safety/tolerability concerns and a lack/loss of efficacy.⁴

As with any chronic disease, patient adherence to topical psoriasis therapy is low. The high burden of treatment and the substantial effort required to maintain ongoing therapy leads to treatment fatigue. According to published data, approximately 75% of patients³ with psoriasis vulgaris (plaque psoriasis), regardless of severity, manage their disease with topical therapies, which may lead to quicker treatment fatigue as the daily treatment regimen can be cumbersome and time consuming.² Studies in medication adherence in psoriasis have shown that 39-73% of patients do not use their medication as prescribed.^5-7 Factors influencing adherence include patient specific characteristics, disease-related characteristics, treatment satisfaction, cosmetic acceptability and complexity of treatment protocols.⁸ Studies also report that cosmetic acceptability is a key contributor to adherence, with adherence being reduced if treatments are perceived as messy to apply and sticky on the skin.⁹ There is evidence that low adherence to psoriasis therapies may be related to insufficient instruction on how to use the drug, misperceptions regarding possible adverse events (AEs) and mistaken expectations about the speed and degree of improvement.¹

A challenge to the use of currently available topical therapies is that many patients fail to achieve complete or almost complete clearance of their psoriasis.¹⁰ Increasing awareness of the burden of psoriasis and the psychosocial impact of the disease have underscored the clinical need for a topical therapy that is easy to use, cosmetically appealing, rapidly efficacious with short-term use, as well as be able to induce sustained efficacy for long-term maintenance.^8,10

Rationale for New Topicals in Psoriasis

Topical treatment of skin conditions is an ancient technique meant to soothe and cool the skin. This practice transitioned into a scientific technique in the 19th century with evidence demonstrating that topically applied agents could impact the skin and offer systemic benefits. A growth in the understanding of skin architecture, topical drug formulation and drug delivery resulted in the ongoing development of topical therapies to address visible skin injury and dermal delivery, ideally optimizing directed delivery of an applied drug. Traditionally, topical therapy carrier vehicles were developed empirically by combining favorite and known ingredients affecting the percutaneous absorption of the drug/active ingredient. There was little consideration of cosmetic acceptability and limited knowledge of the skin penetration/ permeation of the drug at the target site. New materials and a greater understanding of product formulation and consumer acceptability have led to the identification of criteria that constitute the “ideal” vehicle, which include properties such as easy application and removal, nonirritating/nonallergenic, chemically stable, homogenous, bacteriostatic, cosmetically acceptable, pharmacologically inert, and ability to rapidly release the drug for enhanced, controlled or targeted absorption.^11,12

With the knowledge that the topical carrier vehicle can influence the performance of the drug, as well as have a direct effect on the appearance and condition of the skin barrier, new vehicle compositions have been developed. These new vehicles offer improved control of application, increased skin absorption, and the maintenance or improvement to the skin barrier.¹³ Beyond this, compounds of active ingredients with new agents need to offer a combination of higher efficacy and better patient acceptability compared with currently available therapies in order to enhance patient adherence.¹⁰ A simplified dosing schedule, such as once per day, and rapid onset of observed effect are key factors that can improve adherence to topical therapies.^14,15

More important than the carrier or the delivery vehicle, the primary consideration is the active drug and its impact on the inflammatory process responsible for psoriasis. The immune pathogenesis of psoriasis involves dendritic cells, T-cells, keratinocytes and a diverse group of inflammatory mediators (chemokines, cytokines, antimicrobial peptides) that further amplify the inflammatory response and trigger the hyperproliferation of keratinocytes. Once activated, this inflammatory process results in the development of painful, itchy, erythematous plaques covered in silvery scales.¹⁶

Vitamin D receptor agonists (e.g., calcipotriol) and glucocorticoids (e.g., betamethasone dipropionate) have shown benefit in treating psoriasis. Glucocorticoids are known potent anti-inflammatory agents that block multiple anti-inflammatory pathways. Vitamin D receptor agonists appear to enhance the immunosuppressive activity of regulatory T-cells, driving T-cells toward a T helper 2 (Th2) profile while inhibiting Th1/Th17 cells. Calcipotriol has been shown to normalize the pro-inflammatory cytokine cascade in psoriasis, ultimately interrupting the pro-inflammatory feedback loop that drives disease pathogenesis.^17,18 Recent data further supports the benefit of combining betamethasone with calcipotriol. The combination of the two agents showed additive effects, inhibiting the secretion of interleukin (IL)-17A and tumor necrosis factor (TNF)-α by dendritic cells and CD4+ and CD8+ T-cells, as well as reducing the inflammatory response of stimulated keratinocytes. This cellular data supports the enhanced clinical efficacy observed with the combination product, compared to the respective monotreatments in psoriasis patients.¹⁷

Vehicle – Getting it Right

When considering topical dermatological treatment, formulators, clinicians and consumers place extraordinary importance on the type of formulation (i.e., principle of the structural matrix – cream, ointment, solution, foam) and the individual excipients of the topical preparations. This importance has been driven by the visibility of the application site, texture and feel of the applied product on the skin, as well as ease of use. The excipients are responsible for enhancing penetration/permeation of the active ingredients, skin hydration, occlusiveness and stability of the topical preparation. The formulation type is equally important as it impacts several aspects of the topical preparation including: cosmetic acceptability (greasiness, messiness, stickiness, visibility on skin and tactile sensation); ease of use/convenience (spreadability, time required for application and drying, staining of clothes/bedding); and potency of the topical preparation. Clinically, the key question is which formulation types (creams, gels, ointments, foams or liposomes) are better at delivering a drug to the skin, promoting cutaneous absorption and potentially leading to enhanced clinical efficacy. Drug delivery is controlled by the vehicle excipients as these impact partitioning of the active ingredients into, and diffusion through, the stratum corneum (absorption and penetration).^12,19 Traditionally, the choice of vehicle for a particular disease was governed by a classification of preparations and disease/patient factors (e.g., location of disease, skin type, type of disease). The evolution and development of new chemical combinations and entities have driven the need for advancements in vehicle delivery. Thus, modern formulations should be able to facilitate enhanced drug delivery to different layers of the skin as well as extend the release time/activity of delivered drugs.¹²

Foam vehicles were developed to address several needs beyond the effective delivery of active ingredients. The formulation also needs to spread easily on large areas of the skin; not require excessive rubbing into already damaged sensitive skin; not leave a greasy or oily film on the skin after application; and not impart a greasy feeling. Foams are an innovative and easy to apply alternative to creams and ointments. Importantly, with any topical vehicle, the excipients should support the stability and delivery of the active ingredients with the additional benefit of helping repair the skin barrier.¹³ Foams are unique delivery vehicles as they are essentially colloids composed of two or three distinct phases: hydrophilic liquid continuous phase with a foaming agent, throughout which a gaseous dispersion phase is distributed, and sometimes a third hydrophobic dispersed phase. Pharmaceutical aerosol foams commonly exhibit three transition states: liquid in the can, propellant/aerosol as it leaves the can and foam on the skin of the patient.²⁰

In the treatment of psoriasis, the fixed combination of calcipotriol and betamethasone as dipropionate (Cal/BD), in either ointment or gel formulations, has shown superior efficacy and improved acceptability compared with the individual active ingredients.^21,22 The rationale behind the development of the fixed dose combination of Cal and BD (as dipropionate) was to allow the delivery of small amounts (0.005% and 0.05%, respectively) of two very potent drugs within a single formulation. Betamethasone dipropionate is available as micronized particles and can be easily suspended homogeneously whereas calcipotriol, present in a much lower concentration, needs to be dissolved in a carefully selected vehicle component to ensure an even distribution.^23,24 While the fixed dose combinations are established first-line therapies for plaque psoriasis, adherence to the ointment formulation remains a significant challenge as the daily treatment regimen can be cumbersome and time consuming.¹⁰

To address patient needs for an easy to apply topical vehicle offering efficacy in psoriasis – an innovative aerosol foam formulation containing calcipotriol and betamethasone in a fixed dose combination was developed. The Cal/BD aerosol foam is a pressurized formulation including an emollient vehicle base, with calcipotriol and betamethasone dissolved in a mixture of volatile propellants, butane and dimethyl ether. Dimethyl ether also acts as a solvent that enhances the solubility of the active ingredients allowing them to completely dissolve, which is in contrast to the ointment and suspension formats.²⁵ Laboratory assays show that the propellants evaporate rapidly after being sprayed on paper, with the calcipotriol and betamethasone remaining completely dissolved in solution (i.e., crystals are absent) creating a stable, supersaturated environment. Further, studies have also demonstrated that the individual components, Cal and BD, in the Cal/BD aerosol foam had significantly greater in vitro skin penetration and increased ex vivo skin permeation (penetration through all skin layers) compared with Cal and BD in the Cal/BD ointment. This is thought to be due to the development of the stable supersaturated solution, leading to greater solubility and skin penetration of the active ingredients, expected to lead to increased skin permeation and increased absorption of actives at the site of action.²⁵

Discussion

The Cal/BD foam has been compared with established topical combination products as well as the individual active ingredients in an extensive clinical trial program. In most studies, the primary efficacy endpoint was “treatment success” as defined by the proportion of patients who were clear or almost clear of psoriasis according to the physician’s global assessment of disease severity (PGA) at week 4, with at least a two-step improvement. Phase II and III studies have demonstrated significantly greater treatment success and at least a 75% reduction in modified psoriasis area and severity index (mPASI75) of the Cal/BD aerosol foam compared to foam vehicle, calcipotriol alone and betamethasone alone, Cal/BD ointment and Cal/BD gel (Table 1) in the treatment of adult patients with psoriasis on the body. The PSO-FAST study demonstrated an early (day 3) significantly greater itch relief and improvement in itch-related sleep loss compared with vehicle in patients receiving the Cal/BD aerosol foam, which was maintained for the remainder of the study.^26,27 These findings are thought provoking as they demonstrate that therapy alleviated common and distressing aspects of psoriasis, including scratching in response to itchiness that can aggravate lesions and sleep loss that can impact daily productivity.³⁰

These studies also showed a significant impact on patient quality of life (QoL) with reductions in Dermatology Life-Quality Index (DLQI) scores. The use of Cal/BD aerosol foam resulted in a significantly greater improvement in DLQI at week 4 versus either the foam vehicle or the Cal/BD gel. DLQI scores of 0/1 achieved by Cal/BD aerosol foam versus Cal/BD gel were, respectively, 46% versus 32% (P=0.013) at week 4 and 61% versus 44% (P=0.03) at week 12.^27,31

Phase II/III studies with the Cal/BD aerosol foam have shown that this new topical agent is efficacious and well accepted in adult patients with psoriasis vulgaris for up to a 4-week treatment period. The safety profile is in alignment with the more established Cal/BD fixed combination ointment. Safety of the Cal/BD aerosol foam versus gel for up to 12 weeks of treatment has been demonstrated in a Phase III trial. Pooled-analysis of the Phase II/III clinical studies showed that the most common AEs with the Cal/BD aerosol foam were nasopharyngitis (n=6, 1.1%) and application-site pain (n=4, 0.7%).^24,26,28 Notably, the Cal/BD aerosol foam has a safety and tolerability profile similar to Cal/BD ointment and the individual active ingredients, demonstrating that the superior efficacy of the aerosol foam does not impact tolerability.¹⁰

The Phase II maximum use systemic exposure (MUSE) study in 35 patients with extensive psoriasis vulgaris (covering 15-30% BSA, with at least 30% scalp involvement), demonstrated that the Cal/BD aerosol foam had no clinically relevant impact on the hypothalamic-pituitary-adrenal (HPA) axis, calcium homeostasis or renal function, demonstrating low systemic absorption of Cal and BD.³²

While long-term data for the Cal/BD aerosol foam is yet to come, 52-week data from the Cal/BD ointment demonstrated that no patients experienced HPA axis suppression and that the fixed dose combination is safe and well tolerated when used longterm.^33-35

Treatment failure, poor clinical outcomes and increased healthcare utilization have been linked to non-adherence to treatment as well as physician recommendations. Adherence to topical agents is related to duration of treatment, complexity of the treatment regimen, as well as patient self-image and QoL.^8,36 Demands associated with disease management can create a significant treatment burden for patients with chronic diseases. This burden combined with general life demands (e.g., job, family) comprises the overall patient workload. Treatment fatigue is common, with disengagement from recommended health behaviors when a person’s workload exceeds their capacity, a primary contributing factor to non-adherence.³⁷ With topical dermatologic products, studies suggest that patients prefer and are more adherent to, certain topical vehicles based on convenience and cosmetic acceptability.³⁸

When considering cost of therapy, it is important to remember both direct (e.g., prescription drug costs, physician visits, treatment in day clinics) and indirect costs (e.g., loss of time from work, loss of income, non-prescription drug costs). These costs are likely exacerbated by non-adherence to medication. In psoriasis particularly, QoL is adversely affected with people coping by avoiding social situations and covering their lesions.⁸ An Ontario study found that greater out-of-pocket expenses was related to a higher rate of cost-related non-adherence.³⁹

Conclusion

The efficacy of a fixed-dose Cal/BD combination is well established in patients with mild-to-moderate psoriasis. With the ongoing clinical challenge of achieving optimal control and adherence to treatment, the Cal/BD aerosol foam was developed to increase the therapeutic options available. The data supports that the Cal/BD aerosol foam offers enhanced efficacy due to improved skin penetration of the active ingredients after the formation of a stable supersaturated solution on the skin. With its further favorable impact on itch and quality of life, this foam formulation has the potential to improve adherence by addressing several unmet needs in patients with psoriasis.

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Introduction

While cold sores may be considered mild and inconsequential compared with many other viral infections, they can be extremely uncomfortable physically, making it painful to eat and talk. Cold sores also cause a huge emotional impact as sufferers change their routines to avoid being seen with an unsightly sore and to prevent spreading the virus to their family and close acquaintances.

Treatment options are available to reduce the discomfort associated with cold sores and to lessen the duration of the outbreak. The newest and most promising clinically demonstrated treatments available are docosanol, a nonprescription viral entry blocking agent, valacyclovir, an antiviral prescription agent, and, soon to be approved antiviral agent, famciclovir. More detailed information on these new treatments can be found in the Continuing Education session Recurrent Herpes Labialis: Assessment and Treatment (at www.skinpharmacies.ca).

Background

Cold sores are most often caused by herpes simplex virus type-1 (HSV-1). Primary infections are usually acquired in early childhood, often from parents or siblings, and more than 70% of children are infected by the age of 14. Once the patient is infected with HSV-1, the virus lies dormant in nerve cells. Reactivation is unpredictable with variable onset and recurrence although it can occur particularly during times of stress or trauma.
This recurrent infection can manifest itself as classical cold sores and frequently results in asymptomatic shedding of virus particles. Recurrent HSV-1 lesions occur in approximately 20%-40% of infected individuals.

Diagnostic Features of Cold Sores

Herpes labialis is an infection caused by the herpes simplex virus, characterized by an eruption of small and usually painful blisters on the skin of the lips, mouth, or the skin around the mouth. These blisters are commonly called cold sores or fever blisters.

Cold sores proceed through seven distinct stages from the prodromal stage (pain, burning, itching, or tingling at the site where the blisters will form) that precedes the blisters to the highly infectious blister to the hard scab. It is important to understand the stages and visual appearance of a cold sore, as treatment is most effective when started at the early stages.

A chart fully describing the stages of a cold sore with images can be found at www.coldsores.ca. Patients also often confuse cold sores with canker sores as they share certain physical characteristics. Distinguishing cold sores from canker sores is important because the two conditions have distinct etiologies, presentations, and outcomes. Cold sores are usually on the outside of the lip or on the skin around the mouth. Canker sores are usually on the inside of the lip or mouth on the mucous membranes or buccal mucosa.

Prevention

Prevention of a future outbreak is important to infected individuals. Patients should be counselled to:

• limit sun exposure and apply sun block frequently to the lips and surrounding skin before going out.
• avoid triggers that can reactivate the virus such as windburn, UV light (sun and tanning booths), dry lips, emotional stress, and fatigue.
• be aware of unpreventable triggers such as
• menstruation, fever, illness, allergic reactions, physical injury, dental injury, and facial trauma.
• exercise caution to avoid transmitting the disease to other body parts or to other individuals.

Self-Help for Prevention

• Use skin protectants, such as moisturizers with a sun protection factor (SPF) of 30 or more, frequently on the lips and surrounding skin especially before sun or wind exposure.
• Avoid triggering situations.
• Get plenty of rest.
• Learn techniques to deal with stress.
• Do not share cutlery, cups, glasses, water bottles, towels, or razors.
• Use proper hygiene, wash hands carefully and frequently.

Medical Treatment

Most cold sores will clear up on their own after 7-10 days. Most treatment options are focused on reducing the discomfort associated with cold sores and lessening the duration of the outbreak. There are some newer options available to prevent the outbreak from progressing beyond the prodromal stage. Things that need to be considered include initiation, duration, magnitude and frequency of the cold sore, as well as accessibility, convenience of treatment to the patient, and cost.

Non-Prescription Treatments

Symptom Support Treatments

• Skin protectants (such as Labello® or Orabase®) provide moisturization as well as a mechanical barrier to guard the skin and lips from irritants.
• Topical analgesics/anesthetics suppress the sensory receptors, preventing the transmission of pain sensation to the brain. They can provide temporary relief of pain and itching. Sensitization and irritation can occur from these products.
• Oral analgesics provide temporary relief from the pain.

Viral Entry Blocking Agent Docosanol (Abreva® Cream)

• Blocks the virus from entering cells and subsequent viral replication.
• Has been clinically proven to reduce both the symptoms (including pain and itching) and the legth of the cold sore outbreak.
• Most effective if it is used at the first sign or symptom of a cold sore (prodromal stage).
• Apply 5 times per day from the time of the initial symptoms for up to 10 days.

Possible Anti-viral Activity, Zinc and Heparin (Lipactin® Gel)

• May disrupt viral entry.
• May help shorten the duration of the cold sore if used early during the outbreak.
• Apply 3-6 times daily for up to 14 days.

Prescription Treatments

Anti-virals/nucleoside analogues reduce the number of infectious virions and slow infection between cells.

Topical

Acyclovir Cream/Ointment (Zovirax®)

• Shown to help reduce the severity of cold sores in the immunocompromised.
• Most effective if used at the first sign or symptom of a cold sore (prodromal stage).
• Apply 4-6 times a day for 10 days.

Oral

Acyclovir (Zovirax®)

• Reduces pain and healing time to crust formation, does not appear to affect progression, size or overall healing time.
• Most effective if used at the first sign or symptom of a cold sore (prodromal stage).
• Dosing: 200mg 5 times a day for 5 days.

Famciclovir (Famvir®)

• Reduces duration, healing time, and pain.
• Currently this drug is indicated only for treatment of recurrent episodes of HSV infections in HIV-infected patients (expanded indications are currently being explored).
• Most effective if used at the first sign or symptom of a cold sore (prodromal stage).
• Dosing: 500mg twice daily for 7 days.

Valacyclovir (Valtrex®)

• Reduces duration, healing time, and pain.
• May help suppress cold sore outbreak if taken during prodromal stage.
• Most effective if used at the first sign or symptom of a cold sore (prodromal stage).
• Indicated for suppression of recurrent episodes of Herpes Simplex Labialis.
• Dosing: 2g every 12 hours for two doses.

Counseling Tips

• Review the self-help tips with patients to help reduce their number of cold sore outbreaks and to limit transmission of the virus.
• Counsel patients on the importance of starting treatment at the first sign or symptom of a cold sore.
• Remind patients to wash their hands before and after applying any topical treatment to their cold sore or touching their lips.
• Inform patients that topical treatments may be best applied with a cotton swab or a gloved finger.

¹Scientific Insights Consulting Group, Mississauga, Ontario Canada
²GlaxoSmithKline, Consumer Healthcare, Oakville, Ontario Canada
³Departments of Medicine (Divisions of Dermatology and Clinical Pharmacology), and Pharmacology, University of Toronto Medical School; and Division of Dermatology, Sunnybrook & Women’s College Health Sciences Centre, Toronto, Ontario, Canada

ABSTRACT

Skin cleansers may be an important adjunct to the regimen of those who use cosmetics, have sensitive or compromised skin, or utilize topical therapies. Cleansers emulsify dirt, oil and microorganisms on the skin surface so that they can be easily removed. During cleansing, there is a complex interaction between the cleanser, the moisture skin barrier, and skin pH. Cleansing, with water, soap or a liquid cleanser, will affect the moisture skin barrier. Soap will bring about the greatest changes to the barrier and increase skin pH. Liquid facial cleansers are gentler, effecting less disruption of the barrier, with minimal change to skin pH, and can provide people with a cleanser that is a combination of surfactant classes, moisturizers and acidic pH in order to minimize disruption to the skin barrier.
Key Words: cleansers, emulsifiers, detergents, surfactants, soaps

Skin cleansers are surface-active substances (i.e., mulsifiers/detergents/surfactants/soaps) that lower the surface tension on the skin and remove dirt, sebum, microorganisms and exfoliated corneum cells in an emulsified form. The ideal cleanser should do this without irritating, damaging or disrupting the skin and the moisture skin barrier. Water alone removes approximately 65% of oil and dirt from the skin, but is less effective at removing oils of cosmetic import and some environmental insults. Soaps are the oldest surfactants, and are chemically defined as the alkali salt of fatty acids with a pH of 9.5-10. Synthetic detergents vary in composition and surfactant types (i.e., anionic, amphoteric, cationic, non-ionic, and silicone) and pH. In modern usage, the term “soap” generally refers to any cleansing agent regardless of chemistry.¹

Skin cleansers consist of the following:
• Water
• Surfactants (to emulsify the debris)
• Moisturizers (to hydrate the skin and maintain the skin barrier)
• Binders (to stabilize the formulation)
• Lather enhancers (found in some products)
• Fillers (generally used to harden bar soaps and cleansers)
• Preservatives (to prevent the growth of microorganisms)
• Fragrance (generally used to mask the odour of surfactants)
• Dyes or pigments (found in some products)

Skin cleansing may disrupt or disturb the moisture skin barrier, affect the skin surface pH, and irritate the skin. The moisture skin barrier protects against transepidermal water loss, chemical insult and xenobiotic penetration while preserving water to moisturize and maintain the smoothness and flexibility of the skin. A compromised barrier has been correlated with psoriasis, ichthyoses, and atopic dermatitis.² Moisturizers, both emollients and humectants, within cleansers can maintain skin hydration as well as maintaining and restoring barrier function.³ Emollients impair evaporation of skin moisture by forming a film on the skin surface to impede water loss. Humectants attract and bind water, drawing it up from the dermis into the epidermis. The acid mantle of the skin plays an integral role in skin barrier function as well as regulating bacterial flora.⁴ Studies have shown that skin barrier regeneration/repair proceeds more slowly at neutral pH (7.2) than at physiological pH 5.5.⁵ Cleansers may also cause irritant or allergic contact dermatitis and this effect is enhanced if the skin barrier is compromised.

Table 1: Different forms of cleansers

Types of Cleansers

Surfactants can be utilized quite differently in personal hygiene products. They are selected for their functionality and ability to act as detergents/emulsifiers and foaming agents. Personal hygiene products include soaps, superfatted soaps, beauty bars, dermatological bars or cakes, liquid cleansers including facial liquid cleansers, antiseptic foaming solutions, antibacterial washes, and emulsions. Table 1 outlines different types of cleansers.

Soap, the most commonly used, is a combination of fats and oils (of animal or vegetable origin) and salt.¹ Soap is the simplest anionic surfactant, forming soap salts in water that emulsify whatever is on the skin surface while increasing the pH of the skin. Soap salts also provoke stratum corneum swelling and loss of natural humectants and water leaving the skin dry and the barrier compromised. Enriching soaps (superfatted soaps and beauty bars) with lanolin, sweet almond oil or glycerin helps to alleviate the drying of the skin.⁶

Dermatological bars or cakes are chemically different from soaps, and contain modified detergents to enhance their use. Weak organic acids and emollients need to be added to lower the pH of the product and reduce drying of the skin caused primarily by anionic surfactants. Liquid cleansers are complex formulations that contain a combination of surfactants including anionic, amphoteric, nonionic, and silicone. Liquid cleansers also offer anti-bacterial activity by maintaining the skin at physiological pH and by the activity of the surfactants that emulsify and encapsulate (depending on surfactant and formulation) bacteria for easy removal. One study demonstrated that, following hand cleansing, a liquid cleanser removed 85% of bacteria while a bar soap was able to remove only 65%.⁷ Other studies have shown a relationship between cutaneous surface pH, bacterial microflora and the influence of skin cleanser. Use of an acidic liquid cleanser led to a reduction in inflammatory acne lesions and the number of Propionibacterium acnes (P. acnes) on the skin.^4,8 Generally, liquid cleansers are mild, have an acidic pH, and have a high rinsibility factor.

Antiseptic foaming and antibacterial washes are used as an adjunct to acne treatment, since they contain bacteriostatic agents. When used properly, these washes may effect a reduction in P. acnes and prevent secondary infections in acne skin, but they are drying and irritating to most skin.

Effectiveness/Recent Research Findings

Surfactants cause the majority of adverse skin reactions and disrupt or disturb the moisture skin barrier as surface debris and microorganisms are removed. Anionic/sodium containing surfactants such as sodium lauryl sulphate, sodium tallowate and sodium stearate have been shown to disrupt lipids in the moisture skin barrier, as well as increase the pH of the skin by as much as 2-3 units.^9,10 Disruption and depletion of barrier lipids and an increased skin pH leads to a compromised skin barrier¹¹ leaving the skin in a negative physiologic state with an increased sensitivity to potential irritants.⁸ Other ?”entler” surfactant types, i.e., amphoteric (cocamidopropyl betaine) and nonionic (propylene glycol), have been shown to cause a range of skin and sensory irritations.^12,13

Preservatives are required in all cosmetic, especially liquid, formulations to prevent the growth and infection by microorganisms. Liquid formulations are also protected from microorganisms by being enclosed in a container, so that the bulk of the formulation remains protected from contamination, which can occur with handling. Preservatives, fragrances and dyes used in cleansers also cause irritant or allergic contact dermatitis. Parabens and formaldehyde donors (e.g., diazolidinyl urea, Quaternium-15, DMDM hydantoin) are the major classes of preservatives. Both classes have reported incidents of allergic and contact sensitivity and dermatitis.^14-16 Some compounds are more allergenic than others and cause greater numbers of reactions. One example is Quaternium-15, which is the sixth most common allergen in cosmetic products.¹⁶

Table 2: Comparison of Cosmetic Liquid Cleansers
*Cost in Canadian dollars to consumer as determined from one supplier (Shopper’s Drug Mart, Ontario, Canada)

Liquid facial cleansers are the most effective and beneficial cleansers for sensitive and compromised skin. Their formulations are complex, utilizing a combination of surfactants, moisturizers, binders and preservatives to form a product that will cause the fewest problems and the greatest benefits. Awell-designed liquid facial cleanser will use nonionic and silicone surfactants. Nonionic surfactants (e.g., polysorbate) combine low irritancy with surfactant class and pH compatibility. Silicone surfactants (e.g., dimethicone), provide both a surfactant that can penetrate follicles and crevices thereby bringing debris to the skin surface, and an emollient that softens the skin and creates a film to impede transepidermal water loss.¹⁷ Silicone surfactants also offer properties such as low irritation, and are noncomedogenic and hypoallergenic. Liquid facial cleansers should also contain a mixture of emollients and humectants to help restore the moisture skin barrier and limit the disruption caused by the surfactant. Tolerance is an issue for people with skin conditions such as rosacea, atopic dermatitis, acne vulgaris and sensitive skin. A compromised skin barrier results in their being more susceptible to the effects of topical treatments including cleansing. A liquid facial cleanser with an acidic pH, nonionic/silicone surfactants, moisturizers, and minimal skin residue (high rinsibility) offers the greatest benefits and synergy with topical or systemic therapy. Although liquid facial cleansers are formulated to be less irritating to the skin, some of its components may disrupt the skin barrier or cause contact sensitivities.

Table 2 outlines five cosmetic liquid cleansers that represent a combination of those recommended by dermatologists and those most popular with consumers in Canada. Some of these products are not available outside Canada, and one (Derma Jel®) is the in-store brand for Shopper’s Drug Mart, a nationwide drugstore chain. Most retailers in Canada have a store brand cleanser that is positioned to compete with Spectro Jel®. However, from an ingredients comparison the products are quite different.

Limitations/Adverse Effects

Liquid cleansers are the best choice for whole body cleansing, but cost can be prohibitive. Liquid facial cleansers are more expensive than soap ($2.20 to $7.50/100mL versus $1.00/bar respectively), but prices also vary widely even within the category. The greatest differences between soaps and liquid cleansers are the degree of disruption to the moisture skin barrier and the change to the skin pH. It is difficult, when reading a product label, to determine the function of each ingredient. Many ingredients have more than one function, and the packaging can also be confusing, i.e., phrases such as no preservatives, no surfactants, and fragrance free can be misleading. For example, propylene glycol is a moisturizer but also provides anti-bacterial and emulsifier activity. The term fragrance free can be used in a product if a natural ingredient (not a synthetic ingredient) is used to alter the scent of the product.

Conclusion

The choice of facial cleanser is important for people with normal skin, as well as for those people with sensitive skin and skin diseases such as atopic dermatitis, acne vulgaris. Liquid facial cleansers are the best choice for facial cleansing as they have an acidic pH, moisturizers and high rinsibility. Within the liquid cleanser category, the least irritating cleanser will contain non-ionic/silicone-based surfactants combined with moisturizers, as they will cause the least disruption to the moisture skin barrier and the normal skin flora.

References

1. Friedman M, Wolf R. Chemistry of soaps and detergents: various types of commercial products and their ingredients. Clin Dermatol 14(1):7-13 (1996 Jan-Feb).
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