21: Topical Transdermal Flashcards
physiology of skin
-stratum corneum
-living epidermis
-dermis
-hair follicles and sweat glands
Stratum corneum
-main barrier to permeation
-brick (dead cells) and mortar (lipid) model
-permeation occurs by partitioning thru lipid material between dead cells
-lipid barrier
-state of hydration related to ease of permeation
Living epidermis
-living cells w/o capillaries
-get nutrition by diffusion from dermis
-source of skin color and tanning
Dermis
-contains capillaries
-drug needs to reach capillaries to achieve systemic action
-contains pain, thermal, tactile sensors
-injury must reach dermis to produce scarring
Hair follicles and sweat glands
-secondary route of drug absorption that bypasses the stratum corneum
Functions of the skin
-containment
-microbial barrier
-chemical/radiation/electrical/thermal barrier
skin pH
-5
-inhibits bacterial growth
-sebum has bacterio/fungostatic fatty acids
Skin as chemical barrier
-permeabiilty resistant
skin as a radiation barrier
-exposure to UV stimulates melanin which absorbed UV rays
skin as electrical barrier
-high impedance to flow of electrical current
-need to treat skin w salt solutions and overcome impedance to measure body potentials
Body temp
-98.6 by dilating/contracting blood vessels or sweating
Topical drug delivery
-local effects on barrier function (surface and stratum corneum effects)
-drug action on the skin’s glands
-effects in deep tissues
Transdermal drug delivery
-systemic drug delivery
Surface effects of topical drug delivery
-Zn oxide paste for diaper rash
-sunblock
-lip balms
-calamine, antibxs, deodorants, soaps
Stratum corneum effects
-emolliency: softening horny tissue
-keratolysis: chemical digestion and removal of horny tissues
drug action on skin glands
-antiperspirants
-acne
-hair removers
antiperspirants
-Al-Cl-
-irritate and close orifice of eccrine glands to impede sweat flow
acne meds
-soap, alc, antibxs
-retinoids reset the process of epidermal proliferation and differentiation = prevents formation of lesions
Topical drug effects in deep tissues
-topical steroids
-NSAIDs
-locak anesthetics
-lighten skin
-skin cancer
Topical Drug Delivery Platforms
-ointments
-pastes
-creams
-gels
-rigid foams
Ointment bases
-hydrocarbon (more hydrophobic)
-silicone
-absorption
-water soluble (less hydrophobic)
Hydrocarbon bases
-petrolatum
-polyethylene dissolved in mineral oil
silicone bases
contain ppolydimethylsiloxane oil
absorption bases
-ointment containing w/o emulsifiers
Water soluble bases
-polyethylese glycol ointment
Pastes
-ointments w high concentration of insoluble solids are added
Creams
-o/w or w/o emulsion
Gels
-liquid phase trapped in matrix of polymer
Rigid foams
-air or gad emulsified in a liquid phase
-liquid phase may contain drug
-aerosol shaving creams, medicated quick-breaking antiseptic foams
Transdermal drug delivery
-some drugs can penetrate skin and enter systemic circulation
-good for drugs that experience high first pass metabolism
Transdermal drug delivery structure
-backing membrane
–drug reservoir w drug molecules
-rate-controlling porous membrane
-skin-contact adhesive
-blood capillary
Transdermal drug delivery permeability
-general inpenetrable
-permeability correlates w drug’s MW and Ko/w
-useful for drugs with high skin permeability and low dose requirement
Permeability equation
log P ~ -2.7 + 0.71*logKo/w - 0.0061M
-P= permeability coefficient
-M= molecular weight
-Ko/w= oil/water partition coefficient
Types of transdermal patches
-membrane-modulated
-adhesive dispersion
-matrix dispersion
Membrane-modulated transdermal patches
-backiing membrane
-drug reservoir
-rate-controlling micropourous membrane
-adhesive
Adhesive dispersion transdermal patches
-backing membrane
-drug reservoir
-rate-controlling adhesive
Matrix dispersion
-backing membrane
-drug + adhesive
slide 15
slide 15
Transdermal nitroglycerin
-half-life: 3 min
-slightly soluble in water
-soluble in common organic solvents
Transdermal nitroglycerin use
-prevent angina due to coronary heart disease
-not for immediate relief of acute attacks
Transdermal rivastigmine use
-indicated for dementia associated w alzheimer’s or parkinsons
transdermal rivastigmine dose
-4.6, 9.5, 13.3 mg/day
Transdermal rivastigmine
-soluble in water, ethanol, acetonitrile, n-octanol, ethyl acetate
-log P: 2.3
-water solubility 2.04mg/mL
-backing film, drug matrix, adhesive matrix, release liner
Transdermal contraceptive
-35mcg ee
-150mcg
-once a week for 3 weeks
-upper arm, abdomen, buttock, back
Matrix-type transdermal system strucutre of xulane
-backing polymer layer
-middle layer: adhesive + matrix + active ingredients
-third layer: release liner
Drug diffusion through skin
-across cellular-intercellular regions
-across lipid intercellular spaces
-across thin lipid layers sandwiched between flattened protein cells
Factors affecting permeability
-hydration
-solubility of drug in stratum corneum
-excipients (solvents, surfactants)
-pH affects ionization
Methods of penetration enhancement
-iontophoresis
-electroporation
-ultrasound
-prodrugs
-chemical
iontophoresis
-uses low voltage electrical current to drive changed drugs through the skin
Electroporation`
-uses high voltage short to creat pores in skin
ultrasound
-use low freq ultrasonic energy to disrupt the stratum corneum
prodrugs
-make lipophilic
Chemical penetration enhancers
-alcohol, DMSO, surfactants, acetone, ethyl acetate
Enhancers
-ionic surfactants
-ascorbate, dithiothreitol
-azone
-DMSO
ionic surfactants
-disorder the lipid layer of stratum corneum to swell and/or leach out some of the structural components, thus reducing the diffusional resistance
Ascorbate, dithiothreitol
-reducing agents
-disrupt disulfide bonds of proteins in keratinized cells
Azone
-nonpolar, oily liquid
-fluidize lipid lamella region of stratum corneum
Dimethyl sulfoxide (DMSO)
-dipolar solvent
-enter aq region of stratum corneum
-interact w the lipid polar heads to expand hydrophillic region between polar heads
slide26
slide26
Types of microneedles
-dissolving microneedles
-hydrogel forming
-seperable
-hollow
Dissolving microneedles
-type of polymeric MN that can degrade or dissolve postinsertion into the skin
-leads to delivery of excapsulated drug at site of application
Hydrogel forming microneedles
-have cross-linked hydrogel structure that can collect interstitial fluid upon skin application to in-situ hydrogel
Separable microneedles
-rapidly dissolvable backing layers
-weaker connections between backing layers and MN tips, or based on hydrogel backing layer
Hollow microneedles
-each needle incorporates a hollow cavitiy within and a bore on the needle tips to which small volumes of drug can be injected
PVP
Patches application sites
-upper chest/back
-upper arm
-flanks
Patch freq
-daily
-BID
-2 weekly
-weekly
-72h
Common errors in transdermal patch administration
-prep
-removal
-application
-monitoring (displacement)
-storage and disposal
Some patients do not realize
-patch must be applied directly to skin (do not tape)
-remove protective liner
-use one at a time
-where to place (rotate)
-when to change
-TSS
-do not cut patches for kids
