Lecture 6 Transdermal Drug Delivery

Question 1

What is a Transdermal Drug Delivery System (TDDS)?

Answer 1

A system that facilitates the passage of therapeutic quantities of drug substances through the skin and into the general circulation for their systemic effects.

Question 2

What are the advantages of TDDS?

Answer 2

Bypass hepatic “first-pass” and gastrointestinal incompatibility
Reduce side effects due to the optimization of the blood concentration time profile
Provide predictable and extended duration of activity
Greater patient compliance due to the elimination of multiple dosing schedules.
Enhance therapeutic efficacy
Reduce frequency of dosage
Reversibility of drug delivery, which would allow for removal of the drug source
Minimize inter/intra-patient variation
Self-administration

Question 3

What are the disadvantages of TDDS?

Answer 3

Only relatively potent drugs are suitable candidates

Contact dermatitis

Question 4

What is the ideal shelf life for a TDDS?

Answer 4

up to 2 years

Question 5

What is the ideal patch size for a TDDS?

Answer 5

Patch size less than 40 cm2

Question 6

What is the ideal dose frequency for a TDDS?

Answer 6

Once a day to once a week

Question 7

What is the ideal aesthetic properties for a TDDS?

Answer 7

Clear, tan or white color

Question 8

What is the ideal packaging for a TDDS?

Answer 8

Easy removal of release liner and minimum number of steps required to apply

Question 9

What is the ideal skin adhesion properties for a TDDS?

Answer 9

no fall-off during dosing

Question 10

What is the ideal skin interactions for a TDDS?

Answer 10

Nonirritating and nonsensitizing

Question 11

What is the ideal drug release for a TDDS?

Answer 11

Consistent pharmacokinetic and pharmacodynamics profiles over time.

Question 12

What are the factors that affect percutaneous absorption?

Answer 12

Drug concentration, surface area, lipophilic: hydrophilic solubilities, Molecular weight, skin hydration, skin thickness, exposure time

Question 13

What is the equation that helps determine the diffusion of drugs across the skin?

Answer 13

J = (KDscCs)/hsc
J = transdermal flux
K = skin-vehicle partition coefficient
Dsc = effective diffusion coefficient
Cs = saturation concentration of the drug
hsc = effective thickness of the stratum corneum

Question 14

What are the percutaneous absorption enhancers?

Answer 14

Chemical enhancers
Iontophoresis
Sonophoresis

Question 15

What do chemical absorption enhancers do?

Answer 15

Increase skin permeability by reversibly damaging or altering the physicochemical nature of the stratum corneum to reduce its diffusional resistance. Increased hydration of the stratum corneum and/or A change in the structure of the lipids and lipoproteins in the intercellular channels through solvent action or denaturation.

Question 16

How do you select a percutaneous absorption enhancer?

Answer 16

Selection is based on efficacy, low dermal toxicity and compatibility with other components.

Question 17

What are the examples of chemical enhancers that can be used?

Answer 17

Acetone, Azone, Dimethyl sulfoxide(DMSO), Ethanol, Oleic acid, Polyethylene glycol, propylene glycol, sodium lauryl sulfate.

Question 18

What is Iontophoresis?

Answer 18

Delivery of a charged chemical compound across the skin membrane using an electrical field.

Question 19

What is sonophoresis?

Answer 19

High frequency ultrasound to enhance transdermal drug delivery.

Question 20

What is a monolithic TDDS?

Answer 20

Monolithic systems incorporate a drug matrix layer between backing and frontal layers.

Question 21

What is a membrane-controlled TDDS?

Answer 21

Membrane controlled systems contain a drug reservoir or pouch, a rate controlling membrane, and backing, adhesive and protective layers.

Question 22

How can you determine if a device is rate-controlled or not?

Answer 22

If the drug is delivered to the stratum corneum at a rate less than the absorption capacity than it has a device that is rate-controlling.

Question 23

When is the skin the rate-controlling factor?

Answer 23

If the drug is delivered to the skin area to saturation, the skin is the rate-controlling factor.

Question 24

What clinical considerations need to be made concerning TDDS?

Answer 24

Site of application
Clean, dry skin
Avoid lotion, etc.
Do not physically alter
Do not tear or cut; remove carefully
Place where it will not be rubbed off
Wear for the full time period
Clean hands before and after application
If irritation results, remove TDDS
Upon removal, fold so adhesive layers touch and seal and discard properly

Question 25

What type of quality control should be done on TDDS?

Answer 25

Stability of the assembled system
Release profile
In vitro assessment of TDDS using diffusion cells
In vivo assessment of TDDS