ic18 transdermal delivery Flashcards
what is the skin anatomy and physiology?
1) stratum corneum (BARRIER TO OVERCOME; HYDROPHOBIC)
- layers of flattened, stratified, keratinised dead cells
- 10um
2) epidermis
- cells are flatter and more keratinised moving up through the layers
3) dermis (TARGET)
- blood vessel, macrophage, mast cell
what is the structure of the stratum cornea that allows drug movement
ordered rigid bilayer structure
access via intercellular lipid domains (lamellar membrane) = allow lipophilic drugs to pass through
possible to pass through via passive diffusion through the corneocytes
other methods of drug movement via transdermal route
via appendages eg sweat ducts, hair follicles,
however low surface area
differences between topical and transdermal delivery
topical: shallow skin penetration only for local delivery
transdermal: deep skin penetration for systemic delivery
advantages of transdermal
1) controlled release
2) no gi degradation/irritation and bypass first pass effect
3) easy termination of input
4) non-invasive
disadvantages of trasndermal delivery
1) variability between individuals/location of adminstration on body
2) stratum corneum = slows absorption
3) skin irritation (potentially causing interactions or removal; could be related to hyper-hydration and retaining moisture)
4) metabolic enzymes
5) BBB
6) systemic side effects
factors affecting transdermal delivery
1) skin condition: age (thinner skin = faster absorption), disease (psoriasis; dry, flaky skin), injury site (open wound = more absorption)
2) skin thickness
3) skin hydration (stratum corneum)
- water occupying the intracellular space = more space between corneocytes
4) stimulation of skin (phonophoresis/ultrasound, iontophoresis, head)
5) physiochemical properties OF DRUG (lipophilicity, diffusion coefficient)
6) permeation enhancers
7) concentration gradient (usually bulk flow; overload transdermal patch)
8) area of contact between formulation and skin (e.g., size of patch)
specific counselling point regarding skin permeation?
dont enter sauna, use electric blanket
= can increase the movement of drug
dont use cream or ointment = oily stop water form escaping = increased hydration enhances permeation of the drug
ideal drug properties of transdermal delivery
<500 da
hba ≤5
hbd ≤10
logp 1-3
unionised
common excipients for patches
preservatives
- exposure to air + placed on skin
solvent/co-solvent
viscosity modifier
- more viscous = slower release
permeation enhancer
adhesives
permeation enhancer
cyclodextrin
glyceryl monooleate
ethanol
propylene glycol
solvent
ethanol
propylene glycol
viscosity modifier
CMC
HPMC
hyaluronate sodium
calcium alginate
carbomer
poly(methyl vinyl ether/maleic anhydride)
matrix polymers
CMC
HPMC
hyaluronate sodium
calcium alginate
HUMECTANTS
hyaluronate sodium
adhesives
calcium alginate
carbomer
poly (methyl vinyl ether/maleic anhydride)
glyceryl monooleate (bioadhesive)
sustained release agent
glyceryl monooleate
mechanism of glyceryl monooleate
glyceryl: hydrophilic
oleate: hydrophobic
act as a surfactant molecule = permeation enhancer by interacting w the bilayer and reducing the integrity of the membrane = improve access
sustained release agent = at high concentrations it can self assemble to form more complex structures
mechanism of HPMC and CMC
straight chain polymer with addition of water = tangle up w/ intermolecular interactions = form network/matrix to hold drugs
factors affecting delivery specific to polymer matrices
1) diffusion coefficient of drug
2) surface area
3) concentration
4) porosity/tortuosity of polymer matrix = determined by intramolecular interactions
packaging considerations
pouches:
- plastic polymer lining to reduce moisture loss/entry
- aluminium lining = prevent light entry
sealed packaging:
- maintain integrity of adhesive and product
- maintain hydration
design of patches (membrane device)
backing layer
drug reservoir
rate controlling membrane
adhesive
design of patches (matrix device)
backing layer
rate controlling matrix (also contains drug)
adhesive
design of patches (drug in adhesive matrix)
backing layer
adhesive containing drug
purpose of backing layer
protection of drugs and contents from water and other factors
other SPECIAL CONSIDERATIONS for transdermal patches
1) release rate
- potential for leaching and extraction of drug into backing/other layer
- temperature
- crystallinity of drug over time (with moisture loss)
2) strength of adhesion
- affected by sweat, hair…
- adhesion between layers
3) disposal
- high concentrations = risk of exposure to others
membrane considerations
polymer matrix
composition/chemistry = if oppositely charged = affect release
thickness
porosity
tortuosity
adhesive considerations (and structure)
silicone, rubber
consists of adhesives and possibly permeation enhancers
liner
protects adhesive
