Tracey C. Vlahovic, DPM FFPM RCPS (Glasg) Clinical Professor, Dept of Podiatric Medicine, Temple Univ School of Podiatric Medicine, Philadelphia, PA  None for this presentation  Ortho Dermatologics, Bako  Stratum corneum forms the “skin barrier”  Corneocytes filled with keratin  Extracellular matrix - lipid enriched  Protective wall  Regulates homeostasis – TEWL  Prevents the entry of Epidermis in Palm/Sole foreign particles and pathogens into the body  Xerosis  Wet to dry foot syndrome  Hyperkeratosis  Psoriasis  Eczema/dermatitis  Lichen planus  Atopic dermatitis  Contact dermatitis  Lichen simplex chronicus  Stasis edema/dermatitis/ulcer  Dyshidrotic eczema  Dermatophyte infection = Skin Barrier Dysfunction  Lies within choosing the proper topical and active ingredient (Wolverton 2001)

 The old rule in dermatology is “If a lesion is dry, wet it; if a lesion is wet, make it dry” BUT…!!!!

 A vehicle can retard TEWL, increase flexibility of the skin, and stabilize the compound as well as drive it into the skin

 A vehicle can make or break a formulation especially if sub-optimal vehicle used  A Vehicle is the non-  Powder active ingredient, but  Gel impacts how the patient  Lotion tolerates the medicine  Cream  Foam  An IDEAL Vehicle is  Spray odorless, non greasy,  Tape easy to apply, non  Emulsion irritating, inexpensive,  Solution stable, cosmetically elegant, and doesn’t  Lacquer leave a residue  Topical Suspension  Ointment—most potent  Cream  Emollient cream  Gel  Lotion—most diluted  Spray *Traditional thinking was that drugs had  Tape to be occlusive (ointment) in order to get  Foam the best penetration and efficacy

*Newer vehicles have changed our mindset

*Changing vehicles can affect efficacy  Steps of percutaneous absorption of a topical:

 A concentration gradient is initiated

 Active drug moves out of the vehicle and into the skin

 Active drug moves deeper into the skin and blood stream  By:  Controlling the partition characteristic between skin and vehicle

 The vehicle itself may enter the skin and may affect diffusion

 The vehicle may cause occlusion and drive the medication’s penetration

 The release of the drug from the vehicle to the skin may control the rate of delivery

 D Piacquadio and A Kligman, JAAD, 1998 SC SC E E D D H&E Untreated 10 µm 10 µm

SC

E SC D E D

10 µm Vaseline Dimethicone 10 µm

SC E SC E D D

Proderm ® 10 µm Proderm ® 10 µm Ghadially R., abstract presented at 7th Annual Caribbean Dermatology Symposium, St Thomas, US Virgin Islands, 2008  Pairing the correct vehicle/drug combination for the type of skin targeted as well as these factors:

 Anatomy: interdigital vs hair baring skin vs large BSA vs plantar surface  WE DEAL WITH A MULTITUDE OF SKIN TYPES ON THE LOWER EXTREMITY: plantar, dorsal, hair bearing, interdigital, nails

 Severity of skin disease (barrier disruption): Class 1 topical steroid vs the lower classes vs condition of the affected skin vs type of lesions present

 Wet lesion vs dry lesion

 Patient occupation, knowledge, and abillity  Palms and Soles need a topical with greater potency = ointment >>> solution, but not the most cosmetically elegant; also foam

 Leg dermatitis: spray for spread-ability or lotion

 Macerated interdigital = gel but what about a cream?

 Moccassin tinea = cream/emollient/emulsion/spray?

 Interdigital and Moccasin tinea = a combination of gel and cream or a topical suspension

 Inflamed skin = increased absorption, so can use a less potent vehicle (ie liquid or cream)  Male vs. female preferences  Men may prefer gel, spray, or foam for their feet because of applying socks  Women may prefer creams for moisturizing

 Age related preferences  Younger patients may prefer gels, foams, sprays and perceive it as a newer concept than cream

Which will lead to the best patient compliance?? What do you see?  If it is psoriasis, DO NOT USE oral steroids!!  Thou shalt not use Medrol Dose Packs  If acute eczema, use prednisone taper  If you can’t tell it’s psoriasis, biopsy

 Don’t use a combination of antifungal and corticosteroid!  Thou shalt not use Lotrisone (clotrimazole and betamethasone)  Tinea incognito  What is it: fungal, bacterial, inflammatory?  Use the appropriate drug  What stage is it: acute, sub-acute, chronic?  Use the appropriate level of steroid  Other medical factors?  A reason to use topical over systemic?  Require topical or systemic therapy?  Chronic vs acute, severity  If you don’t know or treatment fails, biopsy!!!  The first line is a topical corticosteroid:  Class I drugs should be used for 2 weeks to 1 month with NO refills, remember side effects!  Titrate down  Prepare for flares  Add a barrier function cream  Goal: use little to no topical steroid ultimately

Class I steroids: Clobetasol (Clobex, Olux, Temovate) Halobetasol (Ultravate) Betamethasone (Diprolene) Fluocinonide (Vanos) Diflorasone (Psorcon) Class 1 Super Potent:

Clobex Lotion/Spray/Shampoo, 0.05% Clobetasol propionate

Cormax Cream/Solution, 0.05% Clobetasol propionate Diprolene Ointment, gel, lotion, 0.05% Betamethasone dipropionate Olux E Foam, 0.05% Clobetasol propionate Olux Foam, 0.05% Clobetasol propionate Temovate Cream/Ointment/Solution, Clobetasol propionate 0.05% Class 2 Potent:

Diprolene Cream AF, 0.05% Betamethasone dipropionate

Class 3 Upper Mid-Strength:

DFD-01 emollient Spray, 0.05%* Betamethasone dipropionate

Stein Gold L et al, J Drugs Dermatol. 2016 Mar 1;15(3):334-42.  Tazarotene Gel 0.1% T + Diflorasone reduced atrophy by 37%  Ammonium lactate (AL) AL + Clobetasol 35% decrease, 15% decrease occluded  Calcipotriene ointment CP + BP Minimized atrophy in animal model

Kaidbey K, Int J Dermatol. 2001 Jul;40(7):468-71. Lavker RM J Am Acad Dermatol. 1992 Apr;26(4):535-44. S. Kurdykowski et al, poster EADV, 2012  Ointment (8 weeks) –70% marked improvement Skin irritation 10-15% –11% clear

 Cream –50% marked improvement Skin irritation 10-15% –4% clear

 Solution –31% marked improvement Skin irritation 1-5% –14% clear

 Foam –41% clear/almost clear scalp Skin irritation 2% –14-27% clear/almost clear body

J Drugs Dermatol. 2016 Aug 1;15(8):951-7  Size, shape, charge, keratin binding, hydrophobicity  Nature of vehicle, pH, drug concentration  Nail properties: extent of hydration and disease condition  Kobayashi looked at 5-fluorouracil (hydrophilic) vs tolnaftate (lipophilic): tolnaftate had a low nail permeation because of its high molecular weight and low solubility in water  Urea in an aqueous solvent system denatured keratin and allowed permeation of the drug (swells the nail plate, too)

Chem Pharm Bull 46 (11) 1797-1802, 1998  Nail permeability decreases as the molecular weight of the drug increases

BUT

 Nail hydration facilitates diffusion: reduces resistance of a slightly larger molecular weight, but shouldn’t go above 350g/mol

J Control Release. 2015 Feb 10;199:132-44.  Nail is a hydrogel; with permeation depending upon solubility in water or in a hydrated keratin matrix  Solvents that promote diffusion through the skin, don’t seem to work for the nail  The Above azoles are insoluble in water— remember you need something hydrophilic!!  Adding urea to the mixture did not promote passage of the azoles through

Drug Development and Industrial Pharmacy, Volume 24, Issue 7, January 1998, pages 685-690  Vehicles not only drive in the active ingredient, but can affect the skin barrier and efficacy of the medication  Choosing the right vehicle involves: anatomy, pt preference, skin lesion, etc  With the lower extremity, we are dealing with hair bearing, plantar, interdigital, nails—which makes choosing the best topical more complicated  It’s about the steroid class, not the percentage!  Moisturizers should be part of your regimen  The nail is a hydrogel that is hydrophilic, so the same vehicles that are proven for the skin, may be ineffective for the nail THANK YOU!!!! [email protected]