Transdermal Drug Delivery Flashcards
Describe drug delivery to the nail
Mostly Keratinised tissue
80% hard-keratin – drug absorption is limited
Very low drug transport leading
Long duration of treatment
Topical treatment
- Fungal infections (nail lacquer)
- Nail Psoriasis
- Nail biting…
What are the Advantages
of TRANSDERMAL DRUG ADMINISTRATION ?
- Avoids all the disadvantages of the oral route!
- Non-invasive and ease of administration
- Controlled release
o Low frequency of administration (therefore improves compliance) - Drug administration can be stopped quickly (specific to applying a patch, can quickly remove patch)
- Easy to identify in cases of emergency (specific to applying a patch – name of drug applied on patch)
What are the disadvantages
of TRANSDERMAL DRUG ADMINISTRATION ?
- Not suitable for “bolus’’
- Only suitable for potent drugs
- active at doses 10 mg/day)…with the right properties! (small dose)
- Skin sensitisation/irritation
- Skin first-pass effect still possible for some drugs
o Pre-systemic metabolism
• Less extensive than from GIT
o Likely minor role in drug elimination from patch - Mostly in the viable epidermis
o CYT P450 and other metabolic enzymes
Describe the shunt route
Going through appendages of the skin - hair follicles and sweat glands
Describe the trans-epidermal route
- passive transcellular or intercellular diffusion through the stratum corneum, living epidermis and dermis. Mostly aqueous drugs
Describe the intercellular route
- moving inbetween cells, highly lipid environment
What is the protective / physiological barrier for drugs?
The healthy epidermis forms an effective protective barrier
- Mostly enacted by the stratum corneum
Diseases affecting barrier function can affect drug permeation i.e. dry skin
Using oils or strong moisturizer affects how a drug is transported across the skin
Eczema and psoriasis affects the stratum corneum
PHYSIOLOGICAL BARRIERS
Describe from highest to lowest permeability of anatomical areas of body.
- Epigenital region
- Scalp, head and neck
- Trunk (chest, belly, back)
- Arms/Legs
- Palms/soles (thickest skin, lowest drug transport)
What is a good candidate of a drug for transdermal?
Molecular weight
- 100-800 Da (ideal < 400-500 Da)
Octanol-Water Partition coefficient
- 1 < Log P < 4 - 5
Therapeutic dose of ca. 10mg / day
- A good candidate can permeate at a flux of 1 mg/cm2/day
- Impact on size of patch needed
Affinity for the vehicle
- Be good but not too good
Describe the reservoir patch
- Drug in a reservoir
- Presence of a rate-controlling polymer membrane (rate limiting membrane)
o Minimise interpatient variability - Drug may be present in adhesive layer
o Intentional or through diffusion/saturation during storage. Diffusion happens during storage, If drug diffuses out, it can diffuse into the adhesive layer. Can lead to a burst release shortly after application. - Release rate is typically zero-order – release rate is constant
o Controlled by changing the properties of the membrane
Describe the matrix/monolithic layered patch
- May have one or more layers
- Drug may be dissolved or suspended in a polymer matrix, NO membrane controlling the rate
o Controls the release rate (diffusion across the skin control the rate)
o Variable kinetics
Drug-in-adhesive layer (only 2 layers, backing liner and adhesive/drug layer)
- Drug dissolved or dispersed in adhesive polymer
- Typically, first-order release rate. Depends on the size of the patch aswell
o Patient variability
What are the factors affecting DRUG TRANSPORT?
Application site
Eyelid impossible, but hands and soles not a good idea as of friction so patch can be removed !
- Generally applied to the arms, trunk, back of the ear (scopolamine (drug))
Don’t want drugs close to heart or osetrogen to the breast could increase risk of cancer
Skin hydration and general condition
- Broken vs. unbroken skin (disease states)
o Use of moisturisers, scrubs should be avoided (making SC thinner, impacts drug transport)
o Hydration: occlusive barrier created by the patch. Once patient has been left there, the skin underneath could change. So patients are advised to apply patch to different parts of the body.
What Advice to patient would you give for a patch?
- Instructions provided in the PIL
- Alternate sites of application
- May need to cut hair (do not wet-shave or use hair-removal cream)
- Skin should be clean, not too oily, not irritated, broken or callused
- Do not cut or modify the patch
- Remove carefully, taking care no to touch the adhesive
- Press firmly against the skin, hold in place for a few seconds
- Place where it won’t be rubbed off by friction
- Can generally be left while bathing/swimming/showering
- In case of sensitivity/intolerance/irritation, treatment should be re-evaluated
- After removal, fold in half so that the adhesive layers stick together
- Residual drug may be toxic to children and pets
- Advice if patch falls off or was not replaced in time
- IMPORTANT – HOW TO DISPOSE
How do Permeation enhancers improve drug penetration?
- Increasing hydration (also possible through occlusion)
- Reversibly disrupting the skin’s structure (WANT this to be temporary) OR
- Causing structural changes to lipids/lipoproteins
What are chemical enhancers for permeation enhancement?
- Water – increases hydration
- Organic solvents: acetone, ethanol, azone – acts on skin structure and lipoprotein
- Alcohols: ethanol, polyethylene glycol, propylene glycol – “
- Surfactants: sodium lauryl sulfate (SLS), Tween, Span
- Fatty acid – can help to change skin structure
