Topical Flashcards
Stratum corneum
- main barrier to permeation
- the dead cells of the bricks are not permeable
- permeation occurs by going through the lipid material (mortar) between the dead cells (bricks)
Function: lipid protective barrier
STATE OF HYDRATION IS DIRECTLY RELATED TO EASE OF PERMEATION
Living epidermis
- living cells that do not contain capillaries
- obtain nutrition by diffusion from dermis
- source of skin color and tanning
Dermis
- contains capillaries
- DRUGS MUCH REACH THESE CAPILLARIES TO HAVE SYSTEMIC EFFECT
- contains pain, thermal, and tactile sensors
- must reach this layer to cause scarring
Hair Follicles & Sweat glands
- secondary form of drug absorption that bypasses the stratum corneum
Functions of Skin
Containment
- confine the tissues and restrain the movement
Microbial Barrier
- pH is 5 which inhibits growth of bacteria
Chemical Barrier
- permeability resistance of stratum cornerum
Radiation Barrier
- exposure of UV stimulates melanin synthesis absorbing UV rays
Electrical Barrier
- high impedance to flow of electrical current
- must use salt solutions to overcome impedance
Thermal Barrier
- maintains 98.6 degree F
Topical Drug Delivery
local effects on barrier function
- surface effect
- stratum corneum effect
- effects skin’s glands
- effects on deep tissue
Transdermal Drug Delivery
- systemic effects
Topical Local Effects
Surface Effects
- zinc oxide for diaper rash
- sun block/sunscreen
- lip balm
- calamine lotion
- deodorant
- soap
Stratum corneum Effects
- emolliency: softening horny tissue
- keratolysis: chemical digestion and removal of horny tissue
Glands
- Antipersipriants: aluminum chloride
- Acne: soap, alcoholic solution, antibiotics, retinoids
- Hair remover (depilatory)
Deep Tissues
- corticosteroids
- NSAID (diclofenac)
- anesthetic (benzocaine)
- lighten pigmented skin (hydroquinone)
- skin cancer (5-fluorouracil)
Ointments
Hydrocarbon Base (most hydrophobic)
- petrolatum
- polyethylene dissolved in mineral oil
Silicone Base (slightly hydrophobic)
- contains polydimethylsiloxane oil
Absorption Base
- ointment containing W/O emulsifiers
Water Soluble Base (most hydrophilic)
- polyethylene glycol ointment
Pastes
ointment into which a high concentration of insoluble particulate solid is added
Creams
O/W or W/O emulsion
Gels
liquid phase trapped in matrix of natural or synthetic polymer (tragacanth, pectin, carrageenan, methylcellulose)
Foams
air or gas emulsified liquid phase
What type of drugs are we interested in transdermal delivery?
- short systemic 1/2 life
- extensive 1st pass metabolism
Advantages of Transdermal
- good compliance
- constant delivery of drug
Components of Transdermal Patch
Backing membrane
Drug Reservoir
Rate Controlling membrane
Skin contact adhesive
Requirements for Transdermal Drug
- high skin permeability
- low dose requirement (high potency)
Desire hydrophobic small drugs
Types of Transdermal Patch
Membrane Modulated
- backing membrane
- drug reservoir
- rate controlling membrane
- adhesive
Adhesive Dispersion
- backing membrane
- drug reservoir
- rate controlling adhesive
Matrix Dispersion
- backing membrane
- drug + adhesive = matrix
Active Ingredients in Patches
Clonidine (very small; not very hydrophobic)
estradiol/noregestromin
lidocaine
lidocaine + epinephrine
nicotine (very small; not very hydrophobic)
nitroglycerin (very small; not very hydrophobic)
estradiol (very small and hydrophobic)
oxybutynin
scopolamine
tesosterone
fentanyl (relatively small and hydrophobic)
Commonality: small and/or hydrophobic
Example of Membrane Modulated
Nitroglycerin (227 Da)
- 1/2 life: 3 min
- slightly water soluble
- Indication: prevent angina due to CAD
Example of Adhesive Dispersion
Rivastigmine (250 Da)
- sparingly water soluble
- very soluble in ethanol, acetonitrile, n-octanol, ethyl acetate
- LogP: 2.3 (in between)
- Indication: dementia associated with Alzheimer’s Disease/Parkinson’s
- 4.6mg/24h
- 9.5mg/24h
- 13.3/24h
Example of Matrix Dispersion
Xulane
- 150 mcg/day norelgrstromin + 35 mcg/day EE
- Backing Layer: polymer layer for structure support
- Middle Layer: adhesive + matrix + drug
- Third Layer: release liner
- once a week for 3 weeks on upper arm, abdomen, butt, back
Warning
- smoking can cause CV risk
- risk of VTE
* risk is higher for patch than oral because Css is 65% higher
Drug Diffusion in Skin
- across cellular-intercellular regions
- across lipid intercellular spaces
- across thin lipid layers sandwiched between flattened protein cells
Factors Affecting Permeability
Hydration
- more hydrated, great drug permeability
- water with polar head groups of lipid bilayer loosens lipid packing
Solubility
Excipient
- solvent, surfactant
pH
- affects drug ionization status –> desire unionized drug
Alternatives to Help With Permability
Iontophoresis
- uses low voltage electrical current to drive charged drugs through skin
Electroporation
- uses high voltage to create transient pores in skin
Ultrasound
- uses low frequency ultrasonic energy to disrupt stratum corneum
Prodrug
- makes lipophilic (hydrophobic)
Enhancers (most common): alcohol, DMSO, surfactant, acetone, ethyl acetate
Ionic Surfactant
disorders lipid layer of stratum corneum to swell or leach out some structural components reducing resistance
Ascorbate/Diothiothreitol
reducing agent that disrupts disulfide bonds of proteins in cells
Azone
nonpolar, oil liquid that fluidizes intracellular lipid lamella of stratum corneum in the hydrophobic tails
DMSO
dipolar solvent that enters the aqueous region of stratum corneum interacting with lipid polar heads to expand hydrophilic region between the heads
Microneedles
- make the holes mechanically
Type 1: pretreatment to increase permeability before patch is applied
Type 2: needles coated with drug and released while embedded into skin
Common Errors
Preparation
- removal of patch from packaging
- removal of protective foil
- alternation of patch
Removal
Application
Monitoring heat
Storage
