exam 3 lecture 8 topical/transdermal

Question 1

stratum corneum

Answer 1

main barrier to permation
brick & mortar model: bricks (dead cells) mortar (lipid)
dead cells are not permeable
permeation occurs
functions as lipid bilayer
state of hydration is directly related to ease of permeation

Question 2

living epidermis

Answer 2

living cells without capillaries
gets nutrients from dermis
source of skin color and tanning

Question 3

dermis

Answer 3

contains capillaries
drug needs to reach capillaries to have systemic action
contains pain, thermal, tactile sensors
injury must reach dermis to produce scarring

Question 4

hair follicles + sweat glands

Answer 4

secondary route of drug absorbtion that bypasses stratum corneum

Question 5

functions of skin

Answer 5

containment: confine underlying tissues + restrain movment
microbial barrier: inhibits bacterial growth
chemical barrier: permeability resistance of stratum corneum is greater than other parts of body
radiation barrier: uv stims melatonin
electrical barrier: offers high impedance to the follow of electrical current
thermal barrier & body temp regulation: maintains 98.6F

Question 6

topical

Answer 6

local effects on barrier function –> surface + stratum corneum effects
drug action on skin’s glands
effects in deep tissues

Question 7

transdermal

Answer 7

systemic drug delivery

Question 8

topical drug delivery

Answer 8

local effects on barrier function
- surface effects
- stratum corneum effects
- drug action on skin’s glands
- effects on deep tissue

Question 9

ointments

Answer 9

hydrocarbon bases (most hydrophobic): petrolatum/ PEG
silicone bases (slightly hydrophobic): polydimethylsiloxane oil
absorption bases: ointment containing W/O emulsifiers
water soluble bases (most hydrophilic): PEG ointment

Question 10

pastes

Answer 10

feels like solid once applied
ointment with high concentration of insoluble particulate

Question 11

creams

Answer 11

O/W or W/O emulsions

Question 12

gels

Answer 12

liquid phase trapped in matrix of natural or synthetic polymer

Question 13

foams

Answer 13

air/gas emulsified in liquid phase

Question 14

drugs we are interested in for transdermal

Answer 14

drugs with: short t1/2 and extensive 1st pass

Question 15

advantages of transdermal

Answer 15

good compliance, constant release, more local effects

Question 16

components transdermal

Answer 16

backing membrane
drug reservoir
rate-controlling membrane
adhesive

Question 17

transdermal delivery

Answer 17

denerally impenetrable - resistance is stratum corneum
permeability correlates with drugs MW and Ko/w
useful for drugs with high skin permeability and low dose requirement

Question 18

membrane-modulated transdermal

Answer 18

scopalamine + nitroglycerin
backing membrane, drug reservoir, rate controlling membrane, adhesive
example - transd nitroglycerin for prevention of angina

Question 19

adhesive dispersion transdermal

Answer 19

nitroglycerin
backing membrane, drug reservoir, adhesive
ex = transd rivastigmine for alzheimers

Question 20

matrix dispersion transdermal

Answer 20

nitroglycerin
backing membrane, drug + adhesive matrix
ex - transD contraceptive

Question 21

requirement for transdermal patches

Answer 21

MW has to be small

Question 22

drug diffusion through skin

Answer 22

protein rich cells (bricks) are seperated by thing intracellular lipids (mortar)
1. across intracellular regions
2. across lipid intercellular spaces
3. across thin lipid layers sandwiched between flattened cells

Question 23

factors affecting permeability

Answer 23

hydration: greater hydration = greater permeability
solubility of drug in stratum corneum
excipients
pH

Question 24

penetration enhancements

Answer 24

iontophoresis (low voltage electrical current to drive charged drugs through skin)
electroportation (high voltage to create pores)
ultrasound (ultrasonic waves to disrupt stratum corneum)
prodrugs (make lipophilic)
chemical enhancers (alochol, DMSO, acetone, surfactants)

Question 25

ionic surfactants

Answer 25

disorder lipid layer of stratum corneum to swell –> reduces difussional resistance

Question 26

ascorbate/dithiothreitol

Answer 26

reducing agents to disrupt disulfide bonds –> lossens protein layers

Question 27

azone

Answer 27

nonpolar, oily liquid
fluidizes intracellular lipid lamella region of stratum corneum

Question 28

DMSO

Answer 28

dipolar solvent
enters aqueous region of stratum corneum and interacts with lipid polar heads to expand hydrophilic region between polat heads

Question 29

microneedles

Answer 29

pretreatment to increase skin permeability (poke and patch)
coated with drug that is released from needles while embedded in the skin (coat and poke)
hollow microneedles also used fo flow drug solution into skin

Question 30

common errors

Answer 30

preparation: removal of patch from packaging, removal of protective foil, alternation of patch
removal
application
monitoring: influence of heat, patch displacement
storage and disposal