Transdermal Delivery (2) Flashcards
The epidermis and the dermis both sit on the ______ which is a ________ fat layer.
hypodermis; subcutaneous
______ is the rate limiting step of the skin. Why?
stratum corneum; because it is very compact and hard to permeate
T/F There IS blood in the epidermis.
FALSE: NO BLOOD
______ are the major antigen-presenting cells of the skin
langerhan
______ contains blood vessels
Dermis
The stratum cornuem is about _____ microns
10 (dry)-20
Transdermal patch acts in the ______ while ointments, cream act _____
bloodstream (use the skin as a route of administration); on the skin (localized)
Drugs only need to pass the ____ to the into the blood
epidermis
What do sebaceous glands secrete?
oil
What is the purpose of the sebum secreted by the sebaceous glands?
to lubricate the skin surface and maintain the pH around 5
_____ disrupts the stratum corneum
shaving
The resistance of the skin includes: (3)
- Rsc (stratum corneum: rate limiting)
- Re (epidermis)
- Rd (dermis)
Transdermal patches help to maintain….
the amount of drug in the blood
When does it make sense to make a patch? (4)
- moderately lipophilic
- short half life
- wide therapeutic index
- dose is low (potent)
What mechanism does transdermal patches use? What does that mean?
passive delivery; drug goes in by diffusion
If a drug is extremely lipophilic? hydrophilic?
lipophilic: it will go into the skin, but not into the blood
hydrophilic: not go into the skin
What are some benefits of transdermal patch? (5)
- absence of first pass metabolism
- sustained release effect (drug concentration goest up–> maintained)
- non-invasive
- ease of self administration
- reduced adverse effects/systemic exposure
The skin is ____ degrees Celsius. (used in Franz diffusion cells)
32
FACTORS AFFECTING SKIN ABSORPTION:
Drug concentration/solubility
If you _____ the drug concentration: ____ the amount that will cross the skin
increase; increase
FACTORS AFFECTING SKIN ABSORPTION:
Partition coefficient?
how drug balance between hydrophilic and lipophilic parts
What is the desired LogP for Skin absorption?
1-3.5
If the LogP is negative then?
hydrophilic: not cross the skin
If the LogP is greater than greater than 3.5?
lipophilic: will cross the skin–> not go into the blood
FACTORS AFFECTING SKIN ABSORPTION:
Surface Area
When you ____ the surface area, you _____ the strength
increase: increase
FACTORS AFFECTING SKIN ABSORPTION:
If you ____ the temperature: _____ the amount of drug going into the body
increase: increase
For transdermal patches the ideal saturation is around…
90%
What is the driving force for the delivery of the transdermal patch for increasing concentrations?
thermodynamic activity, which also depends on the vehicle
flux?
amount of drug that crosses the skin in a defined area (ug/sq cm/h)
What is the ideal permeant flux for a transdermal patch?
1 mg/sq cm/day= 10 mg/day
What are the types of transdermal systems? (2)
- reservoir membrane-modulated system
- drug-in-adhesive diffusion controlled system (matrix)
T/F With an adhesive(matrix) patch you remove the backing membrane.
FALSE: you remove the protective liner NOT the backing membrane
Where is the drug in an adhesive match?
inside the adhesive which is revealed after the protective liner is removed
The type of patch used depends on ……
the solubility
Acrylate based
Silicone based
Polyisobutylene based are examples of what type of transdermal patch
matrix (adhesive) patch
T/F You SHOULD use an acrylate patch for controlled substances
FALSE: should not
In a reservoir patch, the drug is suspended, so how is the release of the drug controlled?
by the membrane
Where is the loading dose found in reservoir patches?
in the adhesive
What is the reason why reservoir patches are used less commonly?
leaking from the patches
What was the first transdermal product?
transderm-scop (used for motion sickness)
T/F Nicotine patches ONLY have nicotine
TRUE
Using ____ with nicotine patches may act like an enhancer
soap
When are oral narcotics okay to be used with duragesic patches?
for breakthrough pain (immediate release)
One should avoid…. when using a patch (2)
- hairy areas
- placing the patch in the same place over and over
T/F One should touch the sticky surface of the patch?
FALSE: drug will start to go in the blood from fingers–>adhesive gets compromised
T/F It is okay to cut a patch
FALSE: DO NOT cut the patch
After a patch has been applied for the desired time, does it have any drug remaining? If yes, how much?
- the drug does have excess drug because that is required to drive the gradient
- 10-90% remaining depending on the patch design
What could happen if the drug concentration in a patch is supersaturated?
matrix is unstable–> crystallization will occur over time
If a patch falls off, can it be placed back by putting a tape around it? How about an overlay wrap that is included with some patches?
-No for both the tape and the overlay wrap because the adhesive is compromised
What is the surface area of patches on the market?
5-40 sq cm
What are some enhancement technologies for skin microporation? (4)
- microneedles
- thermal ablation
- radiofrequency ablation
- laser ablation
_____ works for drugs that are charged or neutral. use low electric current to push the drug into the skin(via anode)
iontophoresis
_______ uses high voltage for a short period of time
electroporation
_____ uses ultrasound (tested to enhance the transdermal delivery–> drives molecules into and across skin)
phonophoresis , sonophoresis
_______ is creating microscopic pores in the skin
skin microporation
skin ONLY allows ____ and ____ drugs to come across
small and moderately lipophilic
Why can’t proteins pass into or through the skin?
Large molecular weight and hydrophilic
Type of Skin Microneedle:
Needle goes in makes the pores then comes out. Then the patch is applied
SOLID
Type of Skin Microneedle:
- Needle has the drug coated on it
- Needle goes in, drug is left in the skin and then the needle comes out
- No Patch involved
- Not a lot of drug ~1mL
COATED
Type of Skin Microneedle:
Drug is the needle and the needle dissolves in the skin? example
DISSOLVING: maltose
- Which of the following is more likely to be easily delivered through microchannels from a patch applied after microporation?
- IgG (MW 150,000 Da)
- Terbinafine (MW 291.4)
- IgG (MW 150,000 Da) ANSWER
- Terbinafine (MW 291.4): not needed because it is already moderately lipophilic and small
_____ is the defined as the measurement of the quantity of water that passes from inside a body through the epidermal layer (skin) to the surrounding atmosphere
transepidermal water loss
Pores remain open under ____ conditions
occluded
Maltose micro needles treated skin open to the environment?
NO pores (pores close within 15 hours)
Maltose micro needles occluded by plastic film or by any solution
OPEN pores (up to 72 hours)
How can you determine the drug concentration in the skin? (2)
microdialysis (probe)
tape stripping
