Topical transdermal Flashcards
Define atopic
Atopic: a form of allergy in which a hypersensitivity reaction may occur in a part of the body not in contact with the allergen
Causes of eczema: exogenous
• Exogenous – Irritant contact dermatitis – Allergic contact dermatitis – Photosensitive dermatitis – Dermatophytid (Infective eczematoid dermatitis) (Pruritic rash, immunological in origin)
Causes of eczema
• Endogonous
– Atopic dermatitis
– Seborrheic dermatitis (a condition in which overactivity of the sebaceous glands causes the skin to become oily)
– Nummular eczema
– Dyshidrosis (A vesicular eruption that occurs primarily on the hands and feet. Also called cheiropompholyx, pompholyx)
– Lichen simplex chronicus ((also known as “Neurodermatitis”) is a skin disorder characterized by chronic itching and scratching)
– Asteatotic dermatitis (or eczema craquelé, is characterized by pruritic, dry, cracked, and polygonally fissured skin with irregular scaling)
– Pityriasis alba (common form of pityriasis (usually in children or young adults) characterized by round patches of depigmentation )
– Stasis eczema ((also known as “Congestion eczema,” “Gravitational dermatitis,” “Gravitational eczema,” “Stasis eczema,” and “Varicose eczema”) refers to the changes in the skin due to blood pooling / poor blood flow)
– Juvenile plantar dermatitis
Treatment
- Break the “itch-scratch cycle” – Difficult in infants – may be helped by clothes
- Avoidance of triggers – i.e. food (i.e. spicy foods), contact allergens (i.e. clothing, soap, washing regimens, bath additives), keep nails short to lessen abrasion, inhaled allergens, skin infections, smoke
- Control of exacerbating factors – Hot water during bathing, alcohol – avoid during flare-ups in particular, certain jobs or hobbies that may affect condition, hardness of water, teething, stress
- Use of emollients to help restore skin barrier function and skin hydration – ca. 600g (adult) or 250g (child) per week – use frequently – Patient preference for “brand” or product
- Drying – pat skin dry, try to not rub
Emollients and moisturisers
• For cleansing:
– Use as a soap substitute:
• Dermol 500; Epaderm
– As a bath addative:
• Oilatum and related products
• Dermol 600
– As a bath additive without antispetic / antimicrobial
• Oilatum
• Diprobath
• Balneum (contains urea / soya oil extracts)
• A-Derma
• For treatment of very dry skin
– 50:50 white soft parrafin:liquid paraffin
– Epaderm
• Less effective products:
– However, they may be more cosmetically acceptable and while requiring more frequent use they may also have greater compliance:
– Diprobase
– Doublebase
– E45 and variants (some contain hydrocortisone)
• Aqueous cream has recently been suggested as an issue in such treatments (contain ca. 9% surfactant)
factors
• Patient social, economic and psychological factors (e.g. Age, gender, marital status, employment, drug and alcohol abuse)
• HCP-HC system related factors (e.g. Communication
disease education and motivation)
• Disease related factors (e.g. Visual (facial lesions) disease severity)
• Biopharmaceutical and Cosmeceutical related factors (e.g. Dissatisfaction with Efficacy, local and systemic AEs (or fear of), excessive time and effort, poor sensual and
emotional experience in use)
Reasons for Non Adherence
- low efficacy
- poor cosmetic characteristics
- time consuming
- fear of side effects
- patients preference of drug vehicle
- bad texture
- experienced side effects
- inconvenience
What are the fundamental “barriers” to improving adherence in topical and transdermal formulations?
#3 The stratum corneum barrier: for example; efficacy of polar, low potency compounds such as acyclovir, penciclovir. #2 The obsession with strength-concentration as the only Fickian enhancement strategy; for example, efficacy and safety of corticosteroids, retinoids, D3 etc. #1 The barriers to introduction of “cosmeceutical” technologies into medicinal dermatologicals.
The Higuchi Physical Model (1960): In vitro Transport
F = Cv * Pc * Dc /h
F = Cv * sol Sc * Dc /h
sol V
F ~ Cv * satsolSc * Dc /h
satsol V
F~ DSv * sat sol Sc *Dc /hAppendages
- Deeper epidermal tissues due to pronounced invagination at the hair follicle
- Greater surface area
- Morphologically distinct area (e.g. particulate delivery,
Schaefer et al), and a potential route for drug delivery – how much of the surface is covered by these appendages?
Sebum
- Mixture of cellular debris, secretions from glands and
micro-organisms. - Can be the first barrier to drug absorption
- Thin (0.5 – 10 µm)
- Discontinuous (holes)
- Irregular
- Not really a big barrier to drug diffusion
- Was initially a problem for the first series of transdermal patches
The Stratum Corneum Barrier
- The main (>95%) barrier to percutaneous absorption of
exogenous chemicals - Very thin (ca. 15 microns on the volar forearm) but it is a very lipophilic and very thin stratified epithelium;
- Thickest – soles of the feet
- Thinnest – eyelids, scrotum, behind the ears
- Thickness varies significantly around the body
- Dead, flattened and compacted cells on the outermost surface of the skin
- The “horny” layer
- The main barrier to letting things in and out of the skin (often considered the only barrier. Mediates transepidermal water loss (TEWL))
- Very dense, highly lipid tissue
- Very thin typically, 15-30m in thickness
Horny layer
The horny layer of the skin is a closely meshed system of horny cells (corneocytes) and lipid layers.
Lipid bilayer structure of skin
The lipid system between the horny cells serves as a cement and as a skin barrier. Together with water,
its four main components — fatty acids, triglycerides, ceramides and cholesterol — form the lamellar liquid
crystalline lipid system.
Eczema herpeticum
- Very rare
- Severe disseminated infection
- Risk factor: skin affected by atopic eczema
- Herpes simplex virus
- Very uncomfortable:
- High temperature
- Swollen lymph glands
- Pain on pressure
