Dermal Delivery Flashcards
What are the advantages of skin as a systemic administration route?
avoidance of first-pass effect
- avoids liver metabolism
drug levels can be maintained in the systemic circulation within the therapeutic window
frequency of dosing reduced
improved patient compliance
drug input terminated by removal of patch
What are the disadvantages of skin as a systemic administration route?
skin is a difficult barrier to get across
irritation and sensitization
tolerance inducing drugs
- require washout period
Is skin an organ?
skin is an organ
- largest organ in the body
- covers an area of 1.65-1.85 for the average adult
- it accounts for ≈16% of total body mass
What are the different layers of the skin?
the skin
- epidermis = stratum corner = horny layer = most outer layer
- dermis
- hypodermis
Where do topical applications act on?
surface
- repellants, sun screens, antimicrobials, antiseptics
local
- corticosteroids, cyto-toxics, antiviral, antihistamines, anaesthetics
appendages
- antimicrobials, depilatories
systemic
- nicotine, hormones, scopolamine, fentanyl, nitroglycerin, clonidine
What are the properties of the epidermis?
it is made up of keratinised squamous stratified epithelium
- keratinised = outermost cells have no nuclei and are effectively dead tissue (can flake off)
- squamous = thin flattened cells
- stratified = made up of many layers
tissue is made up of cells laid together in sheets with the cells tightly connected
primary function is protection = penetration barrier
varies in thickness
hydrophobic
What are the properties of the dermis?
constitutes the majority of skin thickness
- papillary layer = acts as a cushion between the epidermis and dermis, interface has many nerve tissues
- reticular layer = very thick as compared to the papillary layer, has capillaries
highly hydrophilic
What are the properties of the hypodermic?
not really important for drug delivery
- does not act as a barrier
function
- heat insulation
- mechanical cushion
has majority of blood supply = are towards the bottom of the skin layers
- target of transdermal delivery
What is the function of the skin?
protective organ
- chemical barrier
= blocks access of exogenous material
= control loss of water, electrolytes and other endogenous materials
= resistance of horny layer to diffusion (appendages offer small fractional area 0.1%)
What is the stratum corneum?
the stratum corneum is the epidermis
- outermost layer
it stops most of exogenous material = >95%
very thin = 15 μm
- it is very difficult to transverse
it is dense, lacks of water and it is lipophilic
What are the pathways through the skin?
across the intact horny layer
- trasncellular
- paracellular = main route
through the hair follicles with the associated sebaceaous glands
via the sweat glands
hair follicles and sweat gland passage is known as transappendageal
What is the horny layer?
horny cells = corneocytes
- makes up the stratum corneum epidermis
the horny layer of the skin is a closely meshed system of horny cells (corneocytes) and lipid layers.
What is the mechanism of the transcellular route?
for lipophilic drugs
- partition in and out of the lipid and keratin domains = between 2 different phases
- more direct route
- limited by solubility of the penetrant in the different phases
What are depots? How do they form within the transcellular route? What drugs are involved?
depots are an accumulation of the drug
depots form within the epidermis of the skin
- topically applied drugs form by binding within the stratum corneum
clotrimazole = hydrophobic
sun screens
anti-fungal
What is the mechanism of the paracellular route?
the space between the corneocytes is less than 0.1 μm wide
follows the path through the lipid domains only
limited by physicochemical properties of the penetrant
for small lipophilic and non-lipophilic molecules (neutral)
