exam 3 lecture 8 topical/transdermal Flashcards
stratum corneum
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
living epidermis
living cells without capillaries
gets nutrients from dermis
source of skin color and tanning
dermis
contains capillaries
drug needs to reach capillaries to have systemic action
contains pain, thermal, tactile sensors
injury must reach dermis to produce scarring
hair follicles + sweat glands
secondary route of drug absorbtion that bypasses stratum corneum
functions of skin
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
topical
local effects on barrier function –> surface + stratum corneum effects
drug action on skin’s glands
effects in deep tissues
transdermal
systemic drug delivery
topical drug delivery
local effects on barrier function
- surface effects
- stratum corneum effects
- drug action on skin’s glands
- effects on deep tissue
ointments
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
pastes
feels like solid once applied
ointment with high concentration of insoluble particulate
creams
O/W or W/O emulsions
gels
liquid phase trapped in matrix of natural or synthetic polymer
foams
air/gas emulsified in liquid phase
drugs we are interested in for transdermal
drugs with: short t1/2 and extensive 1st pass
advantages of transdermal
good compliance, constant release, more local effects
components transdermal
backing membrane
drug reservoir
rate-controlling membrane
adhesive
transdermal delivery
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
membrane-modulated transdermal
scopalamine + nitroglycerin
backing membrane, drug reservoir, rate controlling membrane, adhesive
example - transd nitroglycerin for prevention of angina
adhesive dispersion transdermal
nitroglycerin
backing membrane, drug reservoir, adhesive
ex = transd rivastigmine for alzheimers
matrix dispersion transdermal
nitroglycerin
backing membrane, drug + adhesive matrix
ex - transD contraceptive
requirement for transdermal patches
MW has to be small
drug diffusion through skin
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
factors affecting permeability
hydration: greater hydration = greater permeability
solubility of drug in stratum corneum
excipients
pH
penetration enhancements
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)
ionic surfactants
disorder lipid layer of stratum corneum to swell –> reduces difussional resistance
ascorbate/dithiothreitol
reducing agents to disrupt disulfide bonds –> lossens protein layers
azone
nonpolar, oily liquid
fluidizes intracellular lipid lamella region of stratum corneum
DMSO
dipolar solvent
enters aqueous region of stratum corneum and interacts with lipid polar heads to expand hydrophilic region between polat heads
microneedles
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
common errors
preparation: removal of patch from packaging, removal of protective foil, alternation of patch
removal
application
monitoring: influence of heat, patch displacement
storage and disposal
