IC18 Pharm Tech III

Question 1

What are the 3 layers that a drug must pass through the skin for transdermal delivery?

Answer 1

1. Stratum Corneum
2. Epidermis
3. Dermis

Question 2

What is the stratum corneum made of?

Answer 2

The stratum corneum is made up of:
- 10-20 layers of flattened, stratified, fully keratinised dead cells

The stratum corneum is the top 10µm of skin.

It is also the primary barrier to drug crossing the skin.

Question 3

What is keratin?

Answer 3

Keratin is a hydrophobic protein.

It helps to make the skin hydrophobic and repellent to water.

As skin sheds, the surface skin is lost and the deeper layer of skin moves up & become more keratinised.

Question 4

What is the structure of the stratum corneum?

Answer 4

Brick & Mortar structure.

The cells in the stratum corneum is known as Corneocyte.

The lipid cells that surround the corneocytes is known as the lamellar membrane

Question 5

What are the 2 ways that drug passes through the stratum corneum?

Answer 5

1. Through lamellar membrane
2. Through corneocytes
3. Through appendages (e.g sweat duct, hair follicle)

Question 6

What are the differences between topical and transdermal delivery?

Answer 6

Topical:
- Shallow skin penetration
- For local delivery (e.g cosmetics, antiseptic, anti-inflammatories)

Transdermal:
- Deep skin penetration
- Systemic delivery (e.g Nicotine, Pain relief, Hormonal regulation)

Question 7

What are the advantages of using transdermal delivery?

Answer 7

1. Controlled release
2. No GI degradation
3. Bypasses hepatic 1st pass metabolism
4. Easy termination of input
5. Non-invasive

Question 8

What are the disadvantages of transdermal delivery?

Answer 8

1. Variability between ppl & location of administration on the body
2. Absorption is slow
3. Can cause skin irritation
4. Can be removed by patient
5. Metabolic enzymes on the skin can break down the drug
6. Drug still has to cross the blood brain barrier
7. Can result in systemic side effects.

Question 9

What are the factors that can affect transdermal delivery?

Answer 9

1. Skin condition - age, injury, disease
2. Skin thickness
3. Level of skin hydration
4. Stimulation of skin - heat, ultrasound, phonophoresis
5. Physicochemical properties of drug - lipophilicity, diffusion coefficient
6. Permeation enhancers
7. Concentration gradient
8. Area of contact between formulation & skin.

Question 10

How does transdermal drug delivery reach the brain?

Answer 10

When drug is delivered via transdermal route, it flows into the circulatory system.

The drug will then have to bypass the BBB to access the brain

Question 11

What makes it difficult for drugs to pass the BBB?

Answer 11

1. The BBB blocks 98% of small drug molecules
2. Drugs can only pass through the BBB via tight junctions & transcellular transport.

Question 12

What is the modified Lipinski’s rule for transdermal delivery?

Answer 12

Molecular Weight: <500Da
H bond donors: ≤5
H bond acceptors: ≤10
LogP: 1 - 3
Ionisation state: Unionised

Question 13

There are 2 types of patches used in transdermal delivery.

Can you list the 2 different types of patches?

Answer 13

1. Solution/suspension in reservoirs patches
2. Polymer matrix patches

Question 14

Can you name 4 drugs that uses transdermal delivery?

Answer 14

1. Rotigotine - management of Parkinson’s
2. Fentanyl
3. Oestrogen
4. Nicotine

Question 15

What are common excipients used in patches?

Answer 15

1. Preservatives
2. Solvents/co-solvents
3. Viscosity modifier
4. Permeation enhancers
5. Adhesives

Question 16

How does the polymer matrix in polymer matrix patches affect drug release?

Answer 16

The more complicated & twisted the matrix, the longer the drug takes to diffuse out, resulting in slower release.

The complexity and level of twistedness of the matrix is also known as tortuosity.

Other factors that can affect drug release are:
- Diffusion coefficient of drug
- Surface area
- Concentration of drug in patch

Question 17

What are the components in the packaging of a transdermal patch?

Answer 17

Transdermal patches are stored in individual pouches made of:
1. Plastic lining - prevent moisture loss
2. Aluminum lining - protect from light & prevent moisture loss

The packaging is then sealed to maintain hydration & integrity of the product.

Question 18

There are 2 types of transdermal patches:
1. Solution/suspension in reservoirs patches
2. Polymer matrix patches

What are the layers that make up each transdermal patch?

Answer 18

1. Solution/suspension in reservoirs patches
   - Backing layer
   - Drug reservoir
   - Rate controlling membrane
   - Adhesive
   - Liner
2. Polymer matrix patches
   - Backing later
   - Polymer matrix
   - Adhesive
   - Liner - protects the adhesive

Question 19

What are 3 special considerations for transdermal patches?

Answer 19

1. Release rate of drug from patch
2. Strength of adhesion
   - See if there is leaching of drug into other layers of the patch.
3. Disposal of patch
   - May get into the hands of a small child or animal.

Question 20

What is a counselling point for patients regarding pasting of the transdermal patches on the body?

Answer 20

It is recommended to apply at a different section of the body each day.

Question 21

What is an example of an adhesives?

Answer 21

Silicon

Question 22

What kind of agents are these in a rotigotine patch?

      - Ascorbyl Palmitate
      - Sodium metabisulfite
      - DL-alpha-tocopherol
      - Povidone
      - Rotigotine
      - Silicone

Answer 22

Ascorbyl Palmitate - antioxidant / preservative
Sodium metabisulfite - antioxidant / preservative
DL-alpha-tocopherol - antioxidant / preservative
Povidone - polymer
Rotigotine - API
Silicone - Adhesive

Question 23

What kind of agents are these in a Fentanyl patch?

      - Alcohol
      - Ethylene-vinyl acetate copolymer
      - Hydroxyethyl cellulose
      - Polyester
      - Silicone

Answer 23

Alcohol - Permeation enhancer
Ethylene-vinyl acetate copolymer - Polymer matrix
Hydroxyethyl cellulose - Polymer matrix
Polyester - Polymer backing layer
Silicone - Adhesive