Parenteral & Transdermal Route of Adminstration

Question 1

Describe the properties of intravenous injections

Answer 1

• usually aqueous buffer at neutral pH
• completely solubilised
• no particles except for some nutritional lipids
• hypertonic solutions are possible with slow administration

Question 2

What is intramuscular delivery suitable for?

Answer 2

Prolonged release of oily and particulate doses

Question 3

What is the benefit of higher blood flow in intramuscular drug delivery?

Answer 3

Higher absorption

Question 4

What are the advantages of subcutaneous drug delivery?

Answer 4

• rapid and predictable
• used for self-medication
• used for poorly absorbed and fragile drugs

Question 5

What are the uses of intra-peritoneal drug delivery?

Answer 5

Chemotherapy for abdominal tumours, dialysis in renal failure or for diagnostic imaging agents

Question 6

Give a use for intrathecal drug delivery

Answer 6

Diagnostics - tumours in sub-arachnoid space

Question 7

Where are intracisternal drugs delivered to and what are the risks?

Answer 7

Space around the base of the brain

There is a risk of neurological injury or death by herniation if intracranial pressure is high

Question 8

Give uses for intra-ventricular drug delivery

Answer 8

Infection OR to reduce side effects in malignancy

Question 9

How do needle free injections work?

Answer 9

They force the drug through the skin - they can be spring powered or high pressure gas

Question 10

How do microneedle patches work?

Answer 10

The stratum corner is pierced with short needles to deliver drugs into the skin with minimal invasion. They increase skin permeability by creating micron-scale pathways in the skin - this actively drives drug through.
Can reach the epidermis too.

Question 11

What is the dosage range for transdermal formulations?

Answer 11

5-25mg daily

Question 12

How can transdermal drug penetration be enhanced?

Answer 12

through drug & delivery vehicle modification or through modification of the stratum corneum

Question 13

Give examples of powered penetration enhancement devices

Answer 13

Iontophoresis
Phonphoresis
Electroporation patches

Question 14

What are the routes of transdermal penetration?

Answer 14

1. Directly across the stratum corneum
2. Through sweat ducts
3. Through hair follicles and sebaceous glands

Question 15

What are the properties of the stratum corneum?

Answer 15

• 10-15µm dry
• 40µm hydrated
• layers of keratin rich corneocytes in an intercellular lipid matriculates extruded by keratinocytes
• extruded lipid phase behaviour is different from biomembranes

Question 16

What is the major route for most drugs?

Answer 16

Intercellular route

Route for drugs soluble in lipid regions or in formulation disrupting the lipid regions

Question 17

What is the route for most hydrophilic drugs?

Answer 17

Transcellular
Hydrophilic drugs penetrate the aqueous regions of keratin filaments - but also have to go through intercellular lipid region.

Question 18

What is the ideal molecular weight for a transdermal patch?

Answer 18

<500 Da

but can have <1000 Da

Question 19

What is the ideal melting point for a transdermal patch?

Answer 19

<200°C

Question 20

What is the ideal LogP for a transdermal patch?

Answer 20

Between 1 and 3

Question 21

What is the ideal kinetic half life for a transdermal patch?

Answer 21

<6-8 hours

Question 22

What is the maximum patch size?

Answer 22

50cm2

Question 23

How can a drug vehicle be modified to enhance skin permeation?

Answer 23

• Drug selection
• Use of pro-drug
• Ion pairs, complexes
• Modification of chemical potential
• Form a eutectic system
• Use liposomes or vesicles

Question 24

When would you need to modify the stratum corneum?

Answer 24

If the drug doesn’t have ideal physicochemical properties

Question 25

How can the stratum corneum be modified to enhance skin permeation?

Answer 25

Hydration
Lipid fluidisation
Bypass / removal
Powered electrical devices

Question 26

What happens when a drug is at its highest thermodynamic activity?

Answer 26

It has maximum skin penetration

Question 27

What happens when water is taken up from the skin into the vehicle?

Answer 27

If water is taken up from the skin into the vehicle and acts as a an anti-solvent, thermodynamic activity of the permeant increases drug flux by 5-10X

Question 28

What is a eutectic mixture?

Answer 28

2 components at a certain ratio inhibit crystalline process of each other so that the melting point is less than it would be alone

Question 29

What is the benefit of having a lower melting point?

Answer 29

The greater the solubility in a given organic solvent

Question 30

Define enhancement ratio (equation)

Answer 30

Drug permeability coefficient after enhancer treatment / drug permeability coefficient before enhancer

Question 31

How can permeation be increased through modification of the stratum corneum?

Answer 31

• Disruption og intercellular lipid lamellar structure
• Interaction with intracellular proteins of the stratum corneum
• Improvement of partitioning of a drug, with co-enhancer or co-solvent penetrating stratum corneum.

Question 32

How does hydration of stratum corneum improve permeation?

Answer 32

Alters drug solubility and partitioning. It increases skin hydration, swelling and opening the stratum corneum which leads to increased penetration

Question 33

How do liposomes improve permeation in the stratum corneum?

Answer 33

They hydrate/alter lipid layers

Deformable liposomes have solvent or surfactants to improve stability allowing them to squeeze through channels

Question 34

How does keratin and lipid disruption improve permeation?

Answer 34

The stratum corneum is disordered
Done by:
- mixing homogeneously with lipids, changing solubility
- extracting lipids forming aqueous channels or forming microcavities within the lipid

Question 35

What is the effect of shifting the solubility parameter on permeation?

Answer 35

Shifting the solubility parameter of the skin closer to the drug increases solubility and so increases drug permeation.