topical transdermal revised Flashcards
living dermis
living cells without capillaries
cells get nutrition by diffusion from dermis
source of skin color and tanning
dermis
contains capillaries
drug needs to reach these capillaries to achieve systemic action
contain pain, thermal, and tactile sensors
injury must reach dermis to produce scarring
hair follicles and sweat glands
secondary route of drug absorption that bypasses the stratum corneum
stratum corneum
main (lipid) barrier to permeation
brick and mortar model (dead cells and lipid)
transdermal permeation
state of hydration is directly related to ease
occurs by partitioning through the lipid material between the dead cells
functions of the skin
containment
microbial barrier
chemical barrier
radiation barrier
electrical barrier
thermal barrier
body temp regulation
microbial barrier function
pH of skin is 5, inhibiting growth of bacteria
sebum contains bacteriostatic and fungistatic fatty acids
electrical barrier function
offers high impedance to the flow of an electrical current
needs to treat the skin with salt solution (granular salt suspensions, creams, pastes containing electrolytes) to overcome impedance and measure body potentials
reason for topical drug delivery
local effects (surface vs stratum corneum)
drug action on the skin’s glands
effects in deep tissues
local SURFACE effect examples
zinc oxide paste for diaper rash
sunblock and sunscreen
lip balm for chapped lips
calamine lotion for poison ivy and poison oak
antibiotics
deodorant
medicated soap
local STRATUM CORNEUM effect examples
emolliency – softening of horny tissue
keratolysis – chemical digestion and removal of horny tissue
drug action on skin’s gland
antiperspirants (aluminum chloride)
acne (soap, alcoholic solutions, antibiotics)
hair removers (depilatories)
retinoid
prevent the formation of lesion by resetting the process of epidermal proliferation and differentiation
effects in deep tissues
topical corticosteroids
NSAIDs (diclofenac)
local anesthetics (benzocaine)
lighten excessively pigmented skin (hydroquinone)
skin cancer (5-flurouracil
reason for transdermal drug delivery
systemic purposes
topical systems
ointments
pastes
creams
gels
rigid foams
types of ointments
hydrocarbon based (most hydrophobic, petrolatum)
silicone based
absorption based (O/W)
water soluble based (most hydrophilic)
pastes
ointments into which a high concentration of insoluble particulate solids are added
gels
liquid phase trapped in matrix of natural or synthetic polymer (like tragacanth, pectin, carrageenan, methylcellulose, carboxymethylcellulose, carbopol)
example - topical scalp gel
rigid foams
air or other gas emulsified in liquid phase that contains the drug
examples - aerosol shaving creams, medicated quick-breaking antiseptic foams
drugs suitable for transdermal delivery
drugs with a short systemic half-life, undergo extensive first pass metabolism, thus requiring frequent dosing
high skin permeability
low dose requirement
drug is small and hydrophobic
factoring affecting drug permeability
correlates to drug’s MW and Ko/w
hydration (more hydrated, greater permeability)
solubility of drug
excipients
pH (affects drug ionization status)
black box warning for xulane patch
cigarrette smoking and serious CV risks
risk of VTE
PK profile - 60% higher in women using norelgestromin and EE transdermal system compared to women using an OC (but peak conc is 25% lower)
methods to improve transdermal drug delivery
iontophroesis
electoporation
ultrasound
prodrugs
(chemical) penetration enhancers
ionic surfactants
ascorbate, dithiothreitol
azone
dimethyl sulfoxide (DMSO)
microneedles
iontophroesis
use low voltage electrical current to drive charged drugs through the skin
electoporation
use high voltage to create transient pores in teh skin
early stage, but works well
ultrasound
use low frequency ultrasonic energy to disrupt the skin (Stratum corneum)
ionic surfactants
disorder the lipid layer of stratum corneum to swell and/or leach out some of the structural components
reduces the diffusional resistance
ascorbate, dithiothreitol
reducing agents
disrupt disulfide bonds of protein keratinized cells
azone
nonpolar oily liquid
fluidize intracellular lipid lamella region of stratum corenum
DMSO
dipolar solvent
enter aqueous region of stratum corneum to interact with the lipid polar heads
expands hydrophilic region between the polar heads
microneedles
pretreatment to increase skin permeability before the subsequent application of drug loaded patch
coated with drug that is released from teh needles while skin embedded
hollow ones have been made to flow drug solutions in the skin
potential patch patient errors
must be applied directly to skin
must remove protective liner
must be only one patch at a time
must not cut
where to place
when to change
usage of transparent patches
preparation
removal
application
monitoring (influence of heat, patch displacement)
storage and disposal
