Transdermal RoA

Question 1

Profile of a drug for transdermal delivery?

Answer 1

• Mr <1000, ideally <500
• Melting point <2000 degrees c
• LogP 1-3
• no or few polar centres (carboxylate, zwitterionic structures)
• kinetic half life <6-8 hours
• 50cm2 max patch size
• 5-20mg per day

Question 2

Benefits of IM administration?

Answer 2

prolonged release of oily and particulate doses

quicker than sc

Question 3

Benefits of SC administration?

Answer 3

best for self medication (no need for cleaning)

good for poorlyabsorbed and fragile drugs

Question 4

How do needle free inejctions work?

Answer 4

force drug through skin using high pressure and speeds - either spring powered propelling or high pressure gas

Question 5

What are microneedle patches used for?

Answer 5

so drugs dont have to cross the stratum corneum

Question 6

Methods to increase transdermal drug delivery?

Answer 6

formulation enhancement (drug delivery and vehicle, modification of stratum corneum)

powered penetration (e.g. iontophoresis, phonphoresis, electroporation)

Question 7

What are the three transdermal routes for absorption?

Answer 7

directly across stratum corneum, through sweat ducts, via hair follicles and sebaceous glands

Question 8

Which transdermal routes are appendageal?

Answer 8

sweat ducts, hair follicles, sebaceous glands

Question 9

Disadvantages of delivery through appendageal routes?

Answer 9

very small surface area (0.1%)

Question 10

Challenges of drugs crossing the stratum corneum?

Answer 10

Must be hydrophilic enough to dissolve in keratin filaments, but also dissolve in lipid lamellae/intercellular lipid regions

Question 11

Ways to improve skin permeation via drug vehicle?

Answer 11

drug selection, prodrug use, ion pairs/complexes, chemical potential, eutectic systems, liposomes, vesicles

Question 12

Ways to improve skin permeation via stratum corneum modification?

Answer 12

hydration, lipid fluidisation, bypass/removal, powered devices

Question 13

How is skin permeation improved by modifying chemical potential?

Answer 13

maximum penetration rate achieved when drug is at its highest thermodynamic activity i.e. supersaturated solution

• can be produced using evaporation or co-solvents. clinically done by solvent evaporation from skin (like in creams)
• if water is taken from skin into vesicle, acts as an antisolvent and increases activity a lot. though unstable so requires anti-nucleating agents

Question 14

What is a eutectic mix?

Answer 14

two components at a certain concentration inhibit the crystalline process of eachother - melting point of mix is lower than the individual components

Question 15

What does a lower melting point mean in terms of skin penetration?

Answer 15

better solubility in organic solvent (incl skin lipids)

Question 16

What can stratum corneum modification involve to improve permeation?

Answer 16

• disrupting lipid lamellar structure
• interaction w intracellular proteins
• improvement of partitioning with co-enhancer/solvent

Question 17

How does hydration improve penetration of drugs?

Answer 17

(safest way)

• alters drug solubility and partitioning
• skin hydration causes swelling of SC, opens structures and increased penetration
• occlusion of skin prevents trans-epidermal water loss
• o/w emulsions donate water to skin

Question 18

How do liposomes improve penetration of drugs?

Answer 18

hydrate and/or alter lipid layers

- likely to enter and fuse with stratum corneum lipids

Question 19

What are deformable liposomes?

Answer 19

10-25% surfactant, 3-10% ethanol - act as edge activators, can squeeze through tiny gaps

Question 20

What are ethosomes?

Answer 20

high alcohol content, fluidise lipids

Question 21

What are niosomes?

Answer 21

vesicles composed of non-ionic surfactants