ic18 transdermal delivery

Question 1

what is the skin anatomy and physiology?

Answer 1

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

Question 2

what is the structure of the stratum cornea that allows drug movement

Answer 2

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

Question 3

other methods of drug movement via transdermal route

Answer 3

via appendages eg sweat ducts, hair follicles,

however low surface area

Question 4

differences between topical and transdermal delivery

Answer 4

topical: shallow skin penetration only for local delivery

transdermal: deep skin penetration for systemic delivery

Question 5

advantages of transdermal

Answer 5

1) controlled release

2) no gi degradation/irritation and bypass first pass effect

3) easy termination of input

4) non-invasive

Question 6

disadvantages of trasndermal delivery

Answer 6

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

Question 7

factors affecting transdermal delivery

Answer 7

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)

Question 8

specific counselling point regarding skin permeation?

Answer 8

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

Question 9

ideal drug properties of transdermal delivery

Answer 9

<500 da
hba ≤5
hbd ≤10
logp 1-3
unionised

Question 10

common excipients for patches

Answer 10

preservatives
- exposure to air + placed on skin

solvent/co-solvent

viscosity modifier
- more viscous = slower release

permeation enhancer

adhesives

Question 11

permeation enhancer

Answer 11

cyclodextrin
glyceryl monooleate
ethanol
propylene glycol

Question 12

solvent

Answer 12

ethanol
propylene glycol

Question 13

viscosity modifier

Answer 13

CMC
HPMC
hyaluronate sodium
calcium alginate
carbomer
poly(methyl vinyl ether/maleic anhydride)

Question 14

matrix polymers

Answer 14

CMC
HPMC
hyaluronate sodium
calcium alginate

Question 15

HUMECTANTS

Answer 15

hyaluronate sodium

Question 16

adhesives

Answer 16

calcium alginate
carbomer
poly (methyl vinyl ether/maleic anhydride)

glyceryl monooleate (bioadhesive)

Question 17

sustained release agent

Answer 17

glyceryl monooleate

Question 18

mechanism of glyceryl monooleate

Answer 18

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

Question 19

mechanism of HPMC and CMC

Answer 19

straight chain polymer with addition of water = tangle up w/ intermolecular interactions = form network/matrix to hold drugs

Question 20

factors affecting delivery specific to polymer matrices

Answer 20

1) diffusion coefficient of drug
2) surface area
3) concentration
4) porosity/tortuosity of polymer matrix = determined by intramolecular interactions

Question 21

packaging considerations

Answer 21

pouches:
- plastic polymer lining to reduce moisture loss/entry
- aluminium lining = prevent light entry

sealed packaging:
- maintain integrity of adhesive and product
- maintain hydration

Question 22

design of patches (membrane device)

Answer 22

backing layer
drug reservoir
rate controlling membrane
adhesive

Question 23

design of patches (matrix device)

Answer 23

backing layer
rate controlling matrix (also contains drug)
adhesive

Question 24

design of patches (drug in adhesive matrix)

Answer 24

backing layer
adhesive containing drug

Question 25

purpose of backing layer

Answer 25

protection of drugs and contents from water and other factors

Question 26

other SPECIAL CONSIDERATIONS for transdermal patches

Answer 26

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

Question 27

membrane considerations

Answer 27

polymer matrix

composition/chemistry = if oppositely charged = affect release
thickness
porosity
tortuosity

Question 28

adhesive considerations (and structure)

Answer 28

silicone, rubber

consists of adhesives and possibly permeation enhancers

Question 29

liner

Answer 29

protects adhesive