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January 2012

V e h i c l e s M a t t e rThe Science of TopicalFoam FormulationsTopical drug delivery remainsthe most common methodfor providing dermatologictherapy. Historically, it isassociated with enhanced overallsafety and minimal if any risk ofsystemic exposure and associatedside effects. However, effective topicaldrug delivery presents challenges.Because the epidermal barrieris supposed to prevent entry ofchemicals and noxious materials, 1 itmakes the passage of topicallyapplied drugs difficult. Due to theefficiency of the epidermis in performingits function as a barrier,the amount of topical drug thatgets through the stratum corneumis generally low, even with a welldeveloped vehicle. For example,systemic absorption of corticosteroidsthrough intact, noninflamedskin is typically less thanfive percent of applied drug. 2Topical drug formulators mustdevelop topical drug delivery systemsthat efficiently bypass thebarrier without significantly damagingthe barrier. This presents achallenge. For example, harsh penetrationenhancers could be used tosignificantly degrade the barrierand permit rapid diffusion of drugsContentsReview of Topical Drug Delivery. . . . . . . . . . . . . . . . . . . . . 3What Are Foams? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Foam Formulations in Clinical Practice . . . . . . . . . . . . . . 6Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18About the AuthorsLeon H. Kircik, MD, ChairClinical Associate Professor of DermatologyMount Sinai Medical CenterIndiana University School of MedicinePhysicians Skin Care, PLLC; DermResearch, PLLCLouisville, KYJoseph B. Bikowski, MDClinical Assistant Professor of DermatologyOhio State UniversityBikowski Skin Care CenterSewickley, PADisclosures:Support for this educational initiative was provided by:Onset DermatologicsQuinnova Pharmaceuticals, Inc.Stiefel, A GSK CompanyDr. Bikowski has served on the speaker's bureau or advisory board or is a shareholder orconsultant to Allergan, Coria, Galderma, Onset Dermatologics, Stiefel/GlaxoSmithKline,Intendis, Medicis, Promius, Quinnova, Ranbaxy, and Warner-Chilcott.Dr. Kircik has served as a researcher, consultant, or speaker for Allergan, Coria, Dermik,Ferndale, Galderma, Stiefel/GlaxoSmithKline, Intendis, Medicis, Obagi Medical Products,Inc., Onset Dermatologics, OrthoDermatologics, Quinnova, and Triax.Supplement to Practical Dermatology | January 2012 | 3

V e h i c l e s M a t t e rinto the stratum corneum or deeperskin layers. However, this degree ofinjury would produce a sustainedand undesirable disruption of thebarrier function, setting the stagefor inflammation, infection, andother sequelae and likely prolongingif not exacerbating the existingdisease process. Therefore, alternativemethods of drug delivery areneeded. Acceptable methods ofencouraging drug delivery includethe use of low concentrations ofdesquamating chemicals like propyleneglycol 3,4 —also a solvent andhumectant—to widen the intercellularpathways through which topicallyapplied drugs may pass.Hydration of the stratumcorneum is another method ofenhancing drug delivery. 5 As epidermalcells swell, theaqueous/lipid ratios within theskin are altered, and the cells nolonger resist mechanical sheeringand stress forces. This facilitatesthe passage of molecules betweenepidermal cells. Additionally,hydration is suspected to potentiallyreveal drug binding sitesand/or help to retain drug in theepidermal layers. 5 Hydration alsohelps maintain normal desquamationor may encourage desquamationof the corneocytes and thuscreate passage ways that enhancepenetration of a drug.Hydrating or penetrationenhancingchemicals are just onepart of the topical vehicle deliverysystem. As addressed in previouseditions of Vehicles Matter (availableonline at VehiclesMatter.com),Foams are colloids“composed of two or threedistinct phases: a hydrophilicliquid continuous phase witha foaming agent, throughoutwhich a gaseous dispersionphase is distributed. Theremay be a third hydrophobicdispersed phase.” 7six primary considerations guidethe development of a suitable topicaldrug vehicle. The vehicle must:1. Efficiently deposit the drug onthe skin with even distribution.2. Release the drug so it canmigrate freely to the site ofaction.3. Deliver the drug to the targetsite.4. Sustain a therapeutic drug levelin the target tissue for a sufficientduration to provide apharmacologic effect.5. Be appropriately formulated forthe anatomic site to be treated.6. Be cosmetically acceptable tothe patient.What Are Foams?The most common vehicle types(or more accurately dosage forms,by FDA nomenclature) used indermatology are solutions, ointments,gels, creams, and lotions. Avehicle delivery system that isgrowing in popularity is foams. Afoam is, quite simply, a dispersionof gas in a liquid or solid. 7 Whilesolid or dry foams exist within themedical marketplace (often asdressings), the focus of this discussionis liquid foams. It may benoted at the outset that the foamingaction of liquid (gel, lotion) orsolid (bar) cleansers is not relevantto this discussion of foams.However, cleansers can be formulatedto be dispensed as foams.Foams are colloids “composedof two or three distinct phases: ahydrophilic liquid continuousphase with a foaming agent,throughout which a gaseous dispersionphase is distributed.There may be a third hydrophobicdispersed phase.” 7 Pure liquidswill not foam, therefore foamingand bodying agents are used togenerate and stabilize foams. 7,8The type and amount of foamingagent will influence the stabilityof the foam and its density.Most pharmaceutical foams are,strictly speaking, classified as liquiddosage forms, because that ishow they exist in the can; Thefoam essentially is created at thetime of use and exists only for abrief duration. Upon ejection, thepropellant boils and diffuses whilethe foaming and bodying agentssupport the development of thecrisp, white foam matrix. 8 Anemulsion in the can is convertedto a foam and then back to anemulsion as the foam collapses. 7As Arzhavitina notes, “One shouldconsider pharmaceutical foams asa ‘transition state’ between the4 | January 2012 | Supplement to Practical Dermatology

V e h i c l e s M a t t e rcomparable coverage rates weredetermined. 11 The weight of anFTU of foam vehicle was determinedto be 52.5 +/- 5.7 microg,and there were nine to 12 times asmany FTUs in 100g of vehiclefoam as in 100g of cream or gel.There were 2.3 to 2.8 times asmany FTUs in vehicle foam as in100g of lotion or solution.However, the study showed thatthe area covered by an FTU offoam vehicle was less than thearea covered by an FTU of creamor gel. Nonetheless, the authorsconcluded that the total coveragearea for 100g of foam was similarto that for 100g of other vehicletypes. 11Commonly used propellantsinclude n-butane, isobutene, n-propane, or mixtures of these.These are liquefied under normalpressure, comprising three to 12percent of the concentration of theinitial formulation. Alternatively,systems can use compressed air asan immediately evaporating propellant.Sometimes, along with air,secondary propellants (n-pentane,isopentane, or isobutene) that havedelayed evaporation are used.When these evaporate, they producea cooling effect on the skin.Various physical forces, oftenoccurring simultaneously, maycontribute to the breakdown of afoam once it is dispensed. In simplestterms, these forces involvethe difference in air pressurebetween the air in the bubbles andair in the solution or ambient air(the gradient is higher in smallerbubbles), gravitational forcesbased on differing densities of thephases, and mechanical breakdown.The type and amount of foamingagent affects the stability anddensity of the foam. Polymerssuch as cellulose and xanthamgum can be used to increase foamstability. The specific characteristicsof the foam can be modifiedto establish durability of the foam.Similarly, formulations may purposefullybe formulated to morerapidly dissolve when exposed toheat. For example, some bodyingagents will dissolve when heatedto 32 o C—normal body temperature.8 These thermolabile foamswill remain relatively stable atroom temperature but begin tomelt when they make contact withwarm skin.The density of foams is approximatelyone-tenth that of traditionalvehicles. 7 Easy spreadability offoams is identified as a benefit intreatment of large surface areasand hair-bearing skin, but it is alsoa benefit for inflamed skin. This isbecause ease of spreading reducesthe need to apply pressure ormaintain prolonged contact withthe sensitive diseased area. 9Additional benefits of foamsinclude lack of stickiness or shininessupon application and, conversely,a tendency to absorb andpenetrate quickly. Upon applicationto hair-bearing skin, the foamvehicle breaks down, allowing thesuper-saturated secondary formulationto travel down the hair shaftand enter the stratum corneum viathe appendageal route. Unlike lowviscosity solutions, which can flowaway from the application site,foams tend to remain in the areawhere they are applied.Patients have demonstrated apreference for and a high level ofacceptance of foams.In one study, 20 patients withpsoriasis participated in a focusgroup exploring topical vehiclepreferences. 12 The patients sampleddifferent topical psoriasismedications, assessed the effectsof the vehicles on quality of life(QOL), and completed a preferencemeasure for each vehicle.The focus group sessions resultedin the development of a sevenitempreference measure. Resultsshowed that patients preferredfoam and solution vehicles overcream, gel, and ointment vehicles(p

V e h i c l e s M a t t e rdermatology marketplace werehydroethanolic foam formulationsof corticosteroids. Clobetasol propionate0.05% foam (Olux,Stiefel/GSK) and betamethasonevalerate 0.12% foam (Luxiq,Stiefel/GSK) were introduced inthe early 2000s. These are basedon the VersaFoam-HF vehicle system.Alcohol within the foam isthe primary solvent but also actsas a penetration enhancer,reversibly altering the barrierproperties of the stratumcorneum, and driving drug acrossthe skin membrane via the intracellularroute. This is in contrastto hydration of intercellularspaces in the stratum corneum inorder to facilitate drug delivery. 14Data confirm that foam formulationscan achieve high concentrationsof active corticosteroid inthe skin. In fact, one analysisshowed that clobetasol 0.05%foam achieved effective levels ofskin concentration that were higherthan those achieved throughoral dosing of prednisone. 15 Of furthernote, the analysis showedthat the only other topical formulationsto achieve effective concentrationsin the skin higher thanthose for oral administration werehydrocortisone 2.5% ointment andtriamcinolone 0.1% ointment. 15There is a common perceptionthat, due to their occlusive properties,ointments encourage penetrationof corticosteroids. In fact,some clinicians consider an ointmentformulation of a given corticosteroidto be of a higher poten-Multi-phase FoamsBi-phasic Foams:Solution (solvent, foaming agent,foam stabilizer) + Gas phase(propellant vapor)ValvePropellant(gas phase)Fluid Phase(drug, solvents, etc.)Aluminum or tin canwith non-reactive liningTri-phasic Foams:Lipid phase + Water phase + Gasphase (propellant vapor)Propellant(gas phase)o/w (or w/o) Emulsion(drug, solvents, etc.emulsed with lipids)ActuatorWhen the valve is depressed, the propellant vaporpushes fluids down and up through the valve.Supplement to Practical Dermatology | January 2012 | 9

V e h i c l e s M a t t e rcy class than the same moleculein a lotion or cream vehicle.These ethanolic foam vehiclesare thermolabile, dissolving atbody temperature to provide goodspreadability and cosmetic elegance.As discussed earlier,enhanced drug delivery associatedwith foams does not depend solelyon alcohol content. The naturaldissolution of the foam creates asupersaturated drug solution inthe propylene glycol-rich secondaryformulation that remains onthe skin after evaporation of thealcohol and propellants.Supersaturation provides a drivingforce for drug delivery into theskin.Due to the alcohol content ofhydroethanolic foams, these havebeen associated with a potentialfor transient stinging or burningupon application, which may limittheir usefulness for some patients.Based on the results of studiesdemonstrating high patient satisfactionwith hydroethanolicfoams, 9,13 however, it is evidentthat any temporary applicationsite stinging/burning does not hindertreatment for most patients.Since the introduction of the corticosteroidfoams, other formulationsbased on VersaFoam HF havecome to market. Ketoconazole foam2% (Extina, Stiefel/GSK) is indicatedfor the management of seborrheicdermatitis. In clinical trials ofExtina, a significantly greater percentageof subjects achieved treatmentsuccess (IGA of 0 or 1) usingketoconazole foam than vehicleSeborrheic dermatitis before (left) and after two weeks oftreatment with Extina foam (right).foam (56% and 42%, respectively;p

V e h i c l e s M a t t e rScalp psoriasis before (left) and after twoweeks of treatment with Olux-E foam (right).Photos courtesy of Joseph Bikowski, MD/DermEdOnline.comstinging, burning, and dryness. 20 The propellant ispropane/butane.In a randomized study of subjects 12 years of ageand older with moderate to severe atopic dermatitis,251 subjects were treated with Olux-E Foam and 126subjects were treated with vehicle foam twice dailyfor two weeks. At the end of treatment, 131 of 251subjects (52 percent) treated with Olux-E Foamachieved treatment success, compared with 18 of 126subjects (14 percent) treated with vehicle. Treatmentsuccess was defined by an Investigator’s StaticGlobal Assessment (ISGA) score of clear (0) oralmost clear (1) with at least 2 grades improvementfrom baseline, and scores of absent or minimal (0 or1) for erythema and induration/papulation.In an additional randomized study of subjects 12years of age and older with mild to moderate plaquetypepsoriasis, 253 subjects were treated with Olux-EFoam and 123 subjects were treated with vehicletwice daily for two weeks. At the end of treatment,41 of 253 subjects (16 percent) receiving active treatmentachieved treatment success, compared withfive of 123 subjects (four percent) treated with vehicle.Use of foams is not limited to hair-bearing skin orlarge surface areas. For example, data confirm the

V e h i c l e s M a t t e refficacy of Olux-E foam for nonscalppsoriasis. In a trial of 81individuals with mild to moderatepsoriasis, subjects were randomizedin a 3:1 ratio to apply clobetasolpropionate emollient foam orplacebo to treat psoriasis involvingnonscalp sites. Response wasassessed at weeks 2 (end of treatment)and 4 (follow-up). Theinvestigator's and subject's globalassessment of the response atweek 2 favored clobetasol propionateemollient foam versus vehicle(p

V e h i c l e s M a t t e rPhotos courtesy of Joseph Bikowski, MD/DermEdOnline.comFolliculitis before (left) and after two weeks oftreatment with the Hylatopic Plus Kit (right).In a tape-stripping study conductedto assess reduction intransepidermal water loss (TEWL)associated with various barrierrepair devices, 80 tape-strippedskin sites were evaluated in 10healthy volunteers. While 20 siteswere left untreated as controls,remaining sites were randomizedto treatment with Hylatopic PlusFoam, Hylatopic Foam, orEpiCeram (Promius Pharma).TEWL was measured at baselineand two hours after product application.At two hours,HylatopicPlus Foam achievedroughly 160 percent barrier repairrelative to control sites, and wasthe only treatment to show statisticalsignificance in the degree ofimprovement. 23In vivo assessments usingConfocal Raman Spectroscopyconfirm the barrier repairingeffects of HylatopicPlus. In anopen-label, bilateral comparison,two sites of intact skin and twosites of damaged skin (exposed to1% sodium lauryl sulfate(SLS) for 24 hours to simulatea damaged skin barrier)were identified. Oneintact site and one SLSexposedsite was randomizedto receiveHylatopicPlus three timesdaily, but withheld atleast two hours prior tospectroscopy assessments.Remaining untreated sitesserved as controls. Asearly as two hours postapplication, skin treatedwith HylatopicPlus demonstratedan increase in water and lipid contentcompared with untreatedskin. Improvement continuedthrough to the 48-hour and sevendaytimepoints. 24In a double-blind, split bodystudy involving subjects with mildto moderate symmetrical atopicdermatitis involving body surfacearea greater than or equal to 10percent on the arms or the legs,subjects were randomized to applyhyaluronic acid-based emollientfoam or a reference ceramide-containingemulsion cream to oneside of the body with the othertest product applied to the oppositeside. Twenty subjects wereenrolled. While both formulationsachieved statistically significantimprovement in all clinical signsand symptoms of atopic dermatitisby week 4, only HylatopicPlusFoam achieved statistically significantimprovement in overalleczema severity by week 2.Subjects statistically significantlyfavored the foam in terms of abilityto spread, moisturize, ease ofuse, and lack of odor. Subjectsalso rated the foam higher thanthe cream for effectiveness andability to soothe. 25Another study evaluated theshort-term effectiveness andappeal of HylatopicPlus Foamcompared to pimecrolimus cream1% in the treatment of AD. 26Subjects with mild to moderateatopic dermatitis across a wideage range from children (olderthan two years of age) to olderadults applied HylatopicPlus Foamto one side of the body and pimecrolimuscream 1% to the contralateralside. Primary efficacywas measured by IGA. After fourweeks of treatment, 82 percent oftarget lesions treated with thefoam formulation were scored"clear" (0) or "almost clear" (1).This is compared to 71 percent oftarget lesions treated with pimecrolimusbeing graded as “clear”or “almost clear.” There was nostatistical difference in the efficacyof the two test treatments. Noadverse events associated with useof HylatopicPlus Foam were identifiedin children or adults duringthis four-week study. 27Delevo Foam technology is alsothe basis for BenzEFoam 5.3%(benzoyl peroxide, Onset) andBenzEFoam Ultra 9.8% (benzoylperoxide, Onset). A corneometrystudy confirmed the moisturizingability of BPO emollient foamcompared to a generic BPO 5%gel. BPO 5.3% emollient foam14 | January 2012 | Supplement to Practical Dermatology

V e h i c l e s M a t t e rPhotos courtesy of Joseph Bikowski, MD/DermEdOnline.comAcne before (left) and after four weeks of treatment with BenzEFoam (right).produced a statistically significantincrease in skin moisturizationvalues (p10,000 colonies per cm 2 ), but noclinical signs of acne wereenrolled. Subjects were treatedwith benzoyl peroxide foam 5.3%under supervision by a technicianat the study center daily duringthe first two weeks. After Week 2,application of the BPO foam wasdiscontinued for one week toallow P. acnes regrowth. Beginningat Week 4, subjects were instructedto apply a BPO 8% cleanser(once daily for one week thenonce or twice daily during thenext week) to the same area whenshowering. One week of treatmentwith the BPO 5.3% emollientfoam yielded a 1.93 log reductionin P. acnes counts and a 2.1 logreduction after two weeks. Therewas no reduction in P. acnescounts after treatment with theBPO 8% wash. The lack of P.acnes activity associated with theBPO 8% wash was suggested bythe author to relate to the briefskin contact time with the washoffproduct. Because of thereduced density of follicles andlipids on the trunk, compared tothe face, BPO particles in suspensionin the 8% wash may not havehad sufficient time to be delivered.29Interestingly, the emollient foamappears to optimize delivery ofBPO and is effective even withshort-contact application. In a subsequentpilot study, six patientscolonized with P. acnes on theback applied BPO 5.3% emollientfoam to the back and rinsed it offafter five minutes. Each subjectwas treated under supervision by atechnician at the study center forfive days, followed by two days ofat-home treatment, followed byone more day of treatment at thestudy center for a total of eightdays of treatment. At Day 9, themean reduction in P. acnes was 0.6log10 cfu per cm 2 (p18 years old)all confirmed to be colonized withP. acnes on their backs (>10,000colonies per cm 2 ). 31 For two weeks,each subject applied BPO 9.8%foam to the dry back once dailyand left it in place for two minutesbefore rinsing if off withwater and wiping the area with acloth. This protocol was performedunder supervision at thestudy center during the week andunsupervised at home on theweekends.Mean reduction of P. acnescounts on the back was 0.91 logper cm 2 after one week of treatment,and 1.66 log per cm 2 aftertwo weeks of treatment with BPO9.8% foam (p

V e h i c l e s M a t t e ring adequate antimicrobial effect.BenzeFoam and BenzEFoamUltra contain Micronized BPO particlesthat are smaller than the follicularorifice (~10µm), smallenough to penetrate the pilosebaceousunit. Studies demonstratethat the particles remain uniformlydispersed throughout the productwith limited formation of largeclusters. 28Another emollient foam-basedvehicle formulation is NeoSalusfrom Quinnova, which featuresthe Proderm Technology waterlipidbased delivery system. Themain components of ProdermTechnology (also used in Salvax,Hydro, and Tersi brands) are physiologiclipids palmatic acid andstearic acid. Additionally, it containsthe humectant glycerin andemollient dimethicone, as well asfatty acids (stearic acid/palmiticacid) and povidone.The three primary componentsof Proderm, then, are protective,reparative, and moisturizing. Assuch, Proderm is described as atri-phasic emulsion that, uponapplication, separates into threedistinct layers with variabledepths of penetration: primarilyon the skin, within the straumcorneum, and into the epidermis.First, dimethicone in NeoSalusforms a protective layer on theskin, creating a physical barrieragainst penetration of irritants. Atthe same time, fatty acids penetratethe epidermis where theyplay an active role in skin barrierrestoration and repair. Fluorescentmicroscopy was used to demonstratethe degree of penetrationand the location of fatty acids anddimethicone in NeoSalus relativeto petrolatum. Fluorescent labeledfatty acid was added in traceamounts to NeoSalus, while dimethiconeand petrolatum are spontaneouslyfluorescent. Two hoursafter the formulations wereapplied to hairless mice, skin sampleswere taken for fluorescentmicroscopy. Fluorescencemicroscopy of normal skin showedminimal fluorescence. Skin treatedwith petrolatum showed strongfluorescence in the stratumcorneum, but no penetration intothe viable epidermis, whileNeoSalus-treated skin showeddimethicone in the stratumcorneum and fatty acid penetrationthrough the stratum corneumand throughout the epidermis.Finally, glycerin and other humectantingredients attract moisture tothe stratum corneum.The foam formulation isdesigned to absorb quickly, leavingno residue, and has very goodtolerability. In clinical trials ofNeoSalus including 161 patients,just four reversible adverse eventswere reported (2.48 percent), andnone were serious.Since the product was introducedin Europe in 1998, therehave been only five reports oflocal intolerance reported. Acrossstudies, about three-quarters ofsubjects (76.6 percent) reportedbenefits, improvement in theircondition, and satisfaction withthe product.The hydrating effects of thefoam formulation have beendemonstrated clinically. Anunpublished study of electricalcapacitance in subjects with atopicdermatitis 33 showed improvementsin hydration in skin treated withNeoSalus compared to controlsites. Twenty four subjects withatopic dermatitis but with clinicallynormal-appearing skin wereincluded and completed this randomizedstudy. Subjects underwenta two-week washout periodduring which they used no emollients.At baseline, TEWL measurementswere taken in all subjects.After baseline measurementwas taken, subjects with ADapplied NeoSalus to an area of 100cm 2 on the volar aspect of a randomizedforearm twice or threetimesdaily for two weeks. Theuntreated contralateral forearmwas used as a control. Measurementson days 10 and 21 bothindicated an increase in capacitanceafter treatment and nochange in TEWL, i.e. a moisturizingeffect without an impairmentof skin barrier function.Because of its protectant properties,NeoSalus has demonstratedbenefit as a physical barrier forthe skin against irritants. In a clinicalstudy to determine the efficacyof NeoSalus in controllingchronic inflammation associatedwith hand dermatitis, primarily ofan occupational nature, 31 subjectswith recalcitrant chronic16 | January 2012 | Supplement to Practical Dermatology

V e h i c l e s M a t t e rDespite the relativelyhigher costs associatedwith the development andmanufacture of thesespecialized formulations,data suggest that foams maynot in actual use cost morethan other formulation types.hand dermatitis of at least 12-month duration who were unresponsiveto standard therapy wereenrolled. Subjects receivedNeoSalus with instructions to useat least three times daily, especiallywhile at work. The skin wasevaluated by the investigator andby the patient initially and atweeks 2 and 8 for parametersincluding redness, scaling, fissuring,blistering, and pruritus on a10-point scale. Use of topical corticosteroidswas recorded, and nosystemic therapies other than antihistamineswere allowed. Sixweeks of NeoSalus therapy led toa statistically significant 40 percentmean reduction of hand dermatitisbased on IGA score.Topical corticosteroid use waseither discontinued or markedlyreduced in 53.6 percent of thesubjects. In all, 70 percent of subjectsshowed symptomaticimprovement over the course ofthe study. No adverse effects werenoted. The findings suggest notonly protective but also reparativeeffects for the foam. 32NeoSalus may also protect fromlatex exposure in subjects susceptibleto latex-induced dermal irritation.In a study 33 of 30 volunteerswith a history of intoleranceto latex, but without contacturticaria or contact dermatitis togloves, subjects were treated witha single application of NeoSalusfor 30 minutes on one hand, whilethe other hand remained untreated.Latex gloves were then wornon both hands for 20 minutes. On83 percent of untreated hands,signs and symptoms, such as pruritusand erythema, occurred, versus63 percent of treated hands;the difference was not statisticallysignificant. Additionally, 15 volunteersused NeoSalus before wearinggloves in their occupationalsetting for two weeks, while eightvolunteers served as controls.Among controls, 87.5 percent presentedwith irritant reactions, butonly 66.6 percent of treated subjectsexperienced irritation.Protectant and healing effectsof NeoSalus have been suggestedin studies of patients with incontinence-induceddermatitis. Adultsubjects who used NeoSalus foam,which was well-tolerated in thediaper area, demonstratedimprovement in all symptoms ofdermatitis and maintained skinintegrity through five weeks ofmaintenance use. 33To assess the protectant andanti-inflammatory properties ofNeoSalus, a randomized, controlledclinical study was conductedto compare the irritationcaused by 10% SLS in skin treatedwith NeoSalus and untreated controls.A single application ofNeoSalus prevented irritation andinflammation associated with SLSexposure in susceptible individualsover a 10 day period. Themean irritancy score was 50 percentlower with NeoSalus pretreatmentcompared to without it. 33A survey of hair stylists usingNeoSalus found that a significantproportion (88 percent) indicatedthat the foam protected theirhands from everyday occupationalharm. Of those who typicallyexperienced symptoms of dermatitis,90 percent felt the foamimproved symptoms, such as dryness,chapped skin, or pruritus. 33Data also indicate thatNeoSalus foam may improvewound healing and reduce inflammation.Daily application ofNeoSalus to a split thickness skingraft wound in the pig acceleratedthe rate of wound healing comparedto a wound healing ointmentand standard of care.Application of NeoSalus was associatedwith substantial reductionin the size of the wounds overtime and a significant decrease inthe time to complete closure.Compared to control sites,NeoSalus treatment was associatedwith reduced incidence oflocalized erythema, and itdecreased the amount of time thatexudate was present at the site ofinjury. Histological examinationSupplement to Practical Dermatology | January 2012 | 17

V e h i c l e s M a t t e rPossible Benefits ofFoam Formulations• Comparable cost to otherformulation types.• Ease of application to hairbearingand other skin.• Easy to spread; Reduces need tomanipulate inflamed skin.• High level of patient satisfaction.• May incorporate barrier repairingand/or emollient ingredients.revealed reduced subacute andgranulomatous inflammation andenhanced neovascularization inwounds treated with NeoSalus.An Evolving Delivery FormTopical foam vehicle delivery systemsare relatively new to dermatology,yet they already haveestablished an important role inpatient care. While foam vehicleshave already undergone severalformulation enhancements, additionaladvancements are anticipated.Next generation emollientfoams are especially useful forinflammatory skin conditionsassociated with an impaired epidermalbarrier.Despite the relatively highercosts associated with the developmentand manufacture of thesespecialized formulations, data suggestthat foams may not in actualuse cost more than other formulationtypes. The high level ofpatient satisfaction and ease ofapplication associated with topicalfoams will likely drive continueddevelopment in both the prescriptionand non-prescription skincare realms. ■1. Proksch E, Brandner JM, Jensen JM. The skin: an indispensablebarrier. Exp Dermatol. 2008 Dec;17(12):1063-72.2. Wiedersberg S, Naik A, Leopold CS, Guy RH.Br JDermatol. Pharmacodynamics and dermatopharmacokineticsof betamethasone 17-valerate: assessment of topicalbioavailability. 2009 Mar;160(3):676-86. Epub 2008 Sep6.3. Lanigan RS; Cosmetic Ingredient Review Expert Panel.Final report on the safety assessment of PPG-11 and PPG-15 stearyl ethers. Int J Toxicol. 2001;20 Suppl 4:53-9.4. Lanigan RS; Cosmetic Ingredient Review Expert Panel.Amended final report on the safety assessment of PPG-40butyl ether with an addendum to include PPG-2, -4, -5, -9,-12, -14, -15, -16, -17, -18, -20, -22, -24, -26, -30, -33, -52,and -53 butyl ethers. Int J Toxicol. 2001;20 Suppl 4:39-52.5. Akomeah FK. Topical dermatological drug delivery: quovadis? Curr Drug Deliv. 2010 Oct;7(4):283-96.6. Chourasia R, Jain SK. Drug targeting through pilosebaceousroute. Curr Drug Targets. 2009 Oct;10(10):950-67.7. Arzhavitina A, Steckel H. Foams for pharmaceutical andcosmetic application. Int J Pharm. 2010 Jul 15;394(1-2):1-17.8. Abram and Tomlinson in Handbook of CosmeticScience and Technology. Barel AO, Paye M, Maibach HI,eds. CRC Press. New York. June 2001.9. Purdon CH, Haigh JM, et al. Foam Drug Delivery inDermatology: Beyond the Scalp. American Journal ofDrug Delivery. 2003;1(1):71-75.10. Kurian A, Barankin B. Delivery Vehicle Advances inDermatology. Skin Therapy Letter. http://www.skintherapyletter.com/fp/2011/7.2/2.html11. Feldman SR, Sangha N, Setaluri V. Topical corticosteroidin foam vehicle offers comparable coverage comparedwith traditional vehicles. J Am Acad Dermatol. 2000Jun;42(6):1017-20.12. Housman TS, Mellen BG, Rapp SR, et al. Patients withpsoriasis prefer solution and foam vehicles: a quantitativeassessment of vehicle preference. Cutis. 2002Dec;70(6):327-32.13. Feldman SR, Housman TS. Patients' vehicle preferencefor corticosteroid treatments of scalp psoriasis. Am J ClinDermatol. 2003;4(4):221-4.14. Huang X, Tanojo H, Lenn J, et al. A novel foam vehiclefor delivery of topical corticosteroids. J Am AcadDermatol. 2005 Jul;53(1 Suppl 1):S26-38.15. McClain RW, Yentzer BA, Feldman SR. Comparison ofskin concentrations following topical versus oral corticosteroidtreatment: reconsidering the treatment of commoninflammatory dermatoses. J Drugs Dermatol. 2009Dec;8(12):1076-9.16. Elewski BE, Abramovits W, Kempers S, et al. A novelfoam formulation of ketoconazole 2% for the treatment ofseborrheic dermatitis on multiple body regions. J DrugsDermatol. 2007 Oct;6(10):1001-8.17. Sorilux PI18. Lebwohl M, Sherer D, Washenik K, et al. A randomized,double-blind, placebo-controlled study of clobetasol propionate0.05% foam in the treatment of nonscalp psoriasis.Int J Dermatol. 2002 May;41(5):269-74.19. Kircik LH, Tropmann C. Treatment of Mild-to-ModerateChronic Hand Dermatitis With Clobetasol Propionate0.05% EF Foam: Results From an Open-Label Study. JDrugs Dermatol. 2011 Dec 1;10(12):1398-402.20. Kimball AB, Gold MH, Zib B, et al. 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