Topical transdermal Flashcards

1
Q

Define atopic

A

Atopic: a form of allergy in which a hypersensitivity reaction may occur in a part of the body not in contact with the allergen

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2
Q

Causes of eczema: exogenous

A
• Exogenous
– Irritant contact dermatitis
– Allergic contact dermatitis
– Photosensitive dermatitis
– Dermatophytid (Infective eczematoid dermatitis) (Pruritic
rash, immunological in origin)
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3
Q

Causes of eczema

• Endogonous

A

– 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

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4
Q

Treatment

A
  • 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
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5
Q

Emollients and moisturisers

A

• 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)

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6
Q

factors

A

• 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)

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7
Q

Reasons for Non Adherence

A
  • low efficacy
  • poor cosmetic characteristics
  • time consuming
  • fear of side effects
  • patients preference of drug vehicle
  • bad texture
  • experienced side effects
  • inconvenience
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8
Q

What are the fundamental “barriers” to improving adherence in topical and transdermal formulations?

A
#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.
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9
Q

The Higuchi Physical Model (1960): In vitro Transport

A
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 /h
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10
Q

Appendages

A
  • 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?
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11
Q

Sebum

A
  • 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
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12
Q

The Stratum Corneum Barrier

A
  • 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
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13
Q

Horny layer

A

The horny layer of the skin is a closely meshed system of horny cells (corneocytes) and lipid layers.

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14
Q

Lipid bilayer structure of skin

A

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.

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15
Q

Eczema herpeticum

A
  • 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
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16
Q

Eczema herpeticum

• Treatment:

A
  • Oral aciclovir 400 to 800 mg 5 times daily, or, if available, valaciclovir 1 g twice daily, for 10 to 14 days or until lesions heal.
  • Intravenous aciclovir is prescribed if the patient is too sick to take tablets, or if the infection is deteriorating despite treatment.
  • Secondary bacterial skin infection is treated with systemic antibiotics.
  • Topical steroids are not generally recommended, but may be necessary to treat active atopic dermatitis.
  • Vitamin D supplementation has been recently suggested as an additional treatment
  • Consult an ophthalmologist when eyelid or eye involvement is seen or suspected.
17
Q

Routes across the skin

A
  • Transappendageal
  • Transcellular (aka “paracellular”)
  • Intercellular: The “tortuous” route
18
Q

Formulations

A

Dusting powders

  • Fine particle size with active ingredient
  • Drying/lubricating e.g. antifungal (miconazole) – drug stability

Liquids

  • Soaks – active dissolved in an aqueous solvent
  • Astringents
  • Cooling
  • Leaving a solid film (e.g. potassium permanganate; 13.11 Skin cleansers, antiseptics, and preparations for promotion of wound healing )

Applications
- Simple emulsions or solutions, usually containing a
pesticide
e.g. benzoyl benzoate application (13.10 Anti-infective skin
preparations; acne)

Lotions

  • Aqueous solutions, suspensions or emulsions
  • Cools inflamed skin
  • Deposits a film of solid material e.g. calamine lotion

Paints/tinctures
- Either concentrated aqueous or alcoholic antimicrobial solutions e.g. Trosyl nail solution (tioconazole 28%, fungal nail infections; use for 6 – 12 months)

Collodions

  • Usually organic solvents
  • Mixtures of ether & alcohol
  • Usually painted onto the skin and allowed to dry, leaving a flexible film
  • Contains a polymer (i.e. pyroxlin) and active. e.g. Salicylic Acid Collodion B.P. (i.e. treatment of warts and calluses)
19
Q

Measurement of permeability

A
  • The Franz-type diffusion cell
  • Receptor phase
  • Membrane
  • Donor phase
  • Regular sampling
20
Q

Passive Diffusion

A

…the movement of matter from one region to another
following random molecular motion
- The rate of transfer (the flux) per unit area is proportional to the concentration gradient across a membrane (i.e. skin)
…in the direction of diffusion (from most concentrated to least concentrated regions)
…defined by Fick’s First Law of Diffusion (for isotropic molecules)

21
Q

Permeability Data

A

This is a measure of how much drug passes across the skin in a given period of time - the rate of drug delivery.
- The permeability coefficient is effectively the rate of diffusion (the flux) corrected for other parameters, such as concentration and the thickness of the membrane

22
Q

To calculate the permeability coeffcient (kp) you need:

A
  • amount/area/time/donor concentration.
  • So, your plot should be (say) amount (millimoles) permeated /sq cm of membrane against time in hours.
  • We have plotted conc (millimolar). So find amount in millimoles - using the receptor cell volume and the amount = conc x volume.
  • Divide by area of skin in the diffusion cell (i.e. in a Franz cell).
  • Plot as y axis and find gradient.
  • Divide by applied conc. (millimoles/cm3)
  • this gives kp in units of cm/hour.
  • You must match the length term in your concentration with the area term for your membrane.
23
Q

Fick’s first law of diffusion: start of expt.

A

Above the skin, conc. of drug in formulation = 100%

Below the skin, conc. of drug in formulation = 0%

Flux (rate of transport) is directly proportional to the concentration gradient across the skin

24
Q

Fick’s 1st Law:

A

F ~ DSv * “Pc” * Dc / h

25
Q

Fick’s first Law drives the 3 levels of drug delivery

Technology:

A

Level 1: Drug at or near saturation or supersaturated in the residual phase (DSv technology)

Level 2: Drug at or near saturation or > AND high level of polar solvent (DSv + “Pc” technology)

Level 3: Drug at or near saturation or > AND high level of polar solvent AND a lipid (DSv + “Pc” + Dc technology)

26
Q

Fick’s first law of diffusion: basic form

A
  • Flux (J) α concentration gradient across the skin (∆C m)
    J α ∆Cm
  • Add a proportionality constant (kp – the permeability coefficient) J = kp. ∆Cm
  • or, re-arrange to give:
    kp = J/∆Cm
    This is a very basic form of Fick’s first law
27
Q

Fick’s Law

Implications:

A
  • The rate of diffusion depends on the concentration in the
    formulation?
  • It also depends on how much drug is below the membrane; if it is perfused and carried away, drug delivery will be more effective Does this include the FORM, i.e. whether or not something is ionised?
  • So, your choice of in vitro method, including type of cell and sampling interval, as well as the rate of drug penetration, can significantly effect your measurements
  • The use of a constant (kp) means that you can adjust the
    fluxes of drugs with differing solubility
  • This means that you can use the term kp to compare the rate of permeability of different chemicals
28
Q

Units ficks law

A

Units of flux (J) are:
conc. (or amount, i.e. mM)
unit area (cm2)
time (min or hours, usually hours)

Units of conc. include the volume of receptor cell: i.e. mM per cm3

Units of Kp are cm/time, i.e. cm/hr or cm/s

29
Q

Glucose watch

Four main functions of the watch:

A
  • glucose monitoring/time keeping;
  • review of history, settings and alarms;
  • two-way paging and computer link;
  • emergency communication mode that sends out an emergency signal and informs people of the user’s condition.
  • The option button scrolls through the options within the
    different functions. The Adjust and Start/Stop buttons select and activate the different options.
  • A product simulation gives new users an introduction to the use of the system.