lecture - transdermal drug delivery in CV

Question 1

describe topical drug delivery

Answer 1

local disorder

drug retained within the skin

100s of approved drugs

Question 2

describe transdermal drug delivery

Answer 2

local application

drug delivered to the systemic circulation

to date 19 drugs are approved for this route of administration

Question 3

how is the drug transported through the skin?

Answer 3

drugs needs to be dissolved

diffusion of the drug through formulation

drug at the out layer of the stratum corneum
1.shunt route
2. trasncellaulrar route
3. intercellular

Question 4

what are physiochemical properties affecting the transdermal drug delivery

Answer 4

ability to cross lipid bilayers especially comeocytes

diffusion through aqueous environment viable epidermis

Question 5

what are general properties required for transdermal drug delivery?

Answer 5

molecular weight < 500

log partiiton coefficient in the range 1 to 4

maximum daily dose of 10mg/day

Question 6

what are examples of drugs delivered using transdermal drug delivery?

Answer 6

estradiol

fentanyl

nicotine

Question 7

what are the 5 principles for skin permeation?

Answer 7

1. selection of suitable drug molecule
2. release of drug from formulation (rate, duration)
3. use thermodynamics
4. alcohol can help: partitions into the skin
   sets up transient reservoir for drug to partition into
   drives maximum thermodynamic activity
5. occlusion increases delivery of most drugs:
   hydrates skin by blocking transpeidermal water loss
   EMLA cream (lidocaine, prilocaine) applied under occlusive dressing

Question 8

what are advantages of transdermal patches ?

Answer 8

advantages
- avoids harsh environments of the GI tract eg pH
- drug reaches systemic circulation whilst avoiding 1st pass metabolism
- patches can be easily and quickly removed
- high compliance

Question 9

what is the design of patches like?

Answer 9

the amount of drug delivered is not equal to the amount of drug in the patch

for example, nitro-due 0.2mg/h that is 5mg/day

Question 10

describe the transdermal patch nitro-dur

Answer 10

nitroglycerin as solid dispersion

drug and hydrophilic polymer matrix

matrix diffusion

drug release proportional to area of drug in transdermal patch

delivers 500 micrograms per day

Question 11

describe the transdermal patch transiderm-nitro

Answer 11

nitroglycerin as solid dispersion

drug and liquid silicon matrix

rate controlling membrane

delivers 500micrograms per day

Question 12

what are the transdermal drug delivery systems?

Answer 12

first generation
- transdermal patches in clinical used
- limitation because of the barrier function of the intact startup corneum

second generation
- uses skin permeability enhancers for improving delivery of small molecular weight drugs

third generation
- disruption of stratum corneum barrier eg mcironeedles

Question 13

what are the penetration enhancers requirements for transdermal drug delivery?

Answer 13

increase skin permeability

reversibly disrupting stratum corneum structure

provide an added driving force for transport into the skin

avoid injury to deeper, living tissues

non toxic

mon irritant

compatible with drugs and excipients

patient acceptability

Question 14

where do penetration enhancers act?

Answer 14

penetration enhancers acting on intercellular lipids of stratum corneum

Question 15

give an example of third generation mcroneedle assisted transdermal drug delivery

Answer 15

intradermal influenza vaccine
- delivers vaccine into dermis
targets epidermal langerhans and dendritic cells

elicits strong immune repose (better than IM injection)