Term
| Skin functions (largest body of body 2m squared) |
|
Definition
Protect from environment
maintain temp, electrolyte and fluid balance
component of immune, nervous and endocrine system.
Synthesis and metabolism of lipid, proteins. |
|
|
Term
| Chemicals on skin used for? |
|
Definition
cleansing
improve barrier
systemic abs
beauty and ageing
treat disease for skin and underlying tissue |
|
|
Term
|
Definition
Sunscreens
cosmetics
insect repellent |
|
|
Term
|
Definition
anti-acne
anti-infectives
antiperspirants
hair restorers |
|
|
Term
|
Definition
antihistamines
anaesthetics
antimitotics |
|
|
Term
|
Definition
nitroglycerin
scopolamine
nicotine
NRT |
|
|
Term
|
Definition
analgesics
anti-inflammatories |
|
|
Term
|
Definition
convenience and accessible
Avoid GI tract (acidic)
avoid 1st pass
constant
prolong and rapid termination |
|
|
Term
|
Definition
not for rapid effect
skin permeability
physiochemical properties of drug
limited PK clearance
potential metabolism in skin
tolerance
allergic and irritation to skin |
|
|
Term
|
Definition
Stratum corneum or horny layer 10-20 microns. systemic needs to cross this layer.
Viable epidermis 50-100 (more aqueous therefore easy to move drug across) |
|
|
Term
|
Definition
| contains connective tissue, nerve, lymphatic and vascular vessels |
|
|
Term
| hypodermis and subcutaneous tissue (1-2mm) |
|
Definition
|
|
Term
|
Definition
Main barrier
cells are dehydrated. flattened and stretched
Cells slough off away from blood supply and die daily |
|
|
Term
|
Definition
thru the skin mainly
also hair follicles and sweat ducts
2 routes are intercellular (in the gaps) this space contains a lipid and aqueous region.
transcellular route: directly thru stratum corneum |
|
|
Term
|
Definition
|
|
Term
|
Definition
Passive diffusion
lag time is common
needs a steady state diffusion |
|
|
Term
|
Definition
ficks law: important is K: partition coefficient between applied formulation and skin
D: diffusion coefficient in intercellular channels of diffusion path length
Conc of applied vehicle: assume infinite |
|
|
Term
|
Definition
lipophilic drug and lipophilic vehicle it want partition out of vehicle
lipophilic drug in aqueous vehicle and skin is more lipophilic than vehicle it will partition better
Formulation tend to be at the limit of solubility (maximum flux) |
|
|
Term
| factors influencing skin penetration |
|
Definition
Age: infant have more permeation
condition: injury or disease
site
blood flow
skin metabolism
species (animal or human) |
|
|
Term
| animal skin vs human skin |
|
Definition
| Pig is the closest to humans skin |
|
|
Term
|
Definition
2% potential of liver
endogenous enz: hormones, steroids, inflammatory mediators
exogeneous enz: drugs, pesticides, environment
for example: polycyclic aromatic hydrocarbons in soot: activated in skin and bind to DNA (scrotal cancer) |
|
|
Term
|
Definition
2% potential of liver
endogenous enz: hormones, steroids, inflammatory mediators
exogeneous enz: drugs, pesticides, environment
for example: polycyclic aromatic hydrocarbons in soot: activated in skin and bind to DNA (scrotal cancer) |
|
|
Term
|
Definition
hydration at occlusion
release and abs
vehicle biologically inert
affect skin permeability
enhance flux or SR |
|
|
Term
|
Definition
partitioning from vehicle to skin
solubility of penetration in vehicle
increase solubility in skin
increase diffusion coefficient
disrupt lipid structure
denature proteins |
|
|
Term
| Predicting skin permeation (drug properties) |
|
Definition
MW and vol (>500Da)
Partition coefficient (log P 1-3)
Solubility in oil/water
HB groups (less the better)
melting point (lower is better it is more active) |
|
|
Term
|
Definition
| 1-3, if more lipophilic drug will sit there and not into the aqueous epidermis layers |
|
|
Term
| selection of drug candidates? |
|
Definition
daily dose and potency: (limit few mg/day
clearance kinetics: half life (better if longer)and Vd
physiochemical properties partition coefficient
MW
solubility in oil/water
melting point
tolerance, allergy, irritancy |
|
|
Term
| Assessment of skin penetration |
|
Definition
|
|
Term
|
Definition
hormones
nitroglycerin
fentanyl and buprenorphine
clonidine
scopolamine
nicotine
oxybutynin
selegilene
methylphenidate |
|
|
Term
|
Definition
all CR
reservoir
matrix or drug in adhesive
multiple polymer |
|
|
Term
|
Definition
| has a drug reservoir with a release controlling membrane |
|
|
Term
|
Definition
| has a drug reservoir with a release controlling membrane |
|
|
Term
|
Definition
3 layers
backing
core polymer matrix with drug and penetration enhancer
release liner |
|
|
Term
| DOT matrix Multiple layer |
|
Definition
| allow for smaller patches |
|
|
Term
| skin penetration enhancers |
|
Definition
formulation
chemical
physical
combinations
penetration retarders |
|
|
Term
|
Definition
Chemical enhancer
stop HB between ceramide and therefore loosen lipid bilayer |
|
|
Term
| MOA of chemical enhancers that increase diffusion coefficient? |
|
Definition
disorder the stratum corneum lipids (azone, oleic acid, DMSO, terpenes, surfactants)
extraction of stratum corneum lipids (ethanol acetone, surfactants)
denature proteins in corneocytes |
|
|
Term
| MOA by increase drug solubility in skin |
|
Definition
propylene glycol, ethanol, transcutol.
Can use a combo of increase diffusion coefficient and increase drug solubility in skin |
|
|
Term
| carrier systems: vesicles and particles |
|
Definition
liposomes
transfersomes
niosomes
ethosomes
nanoparticles |
|
|
Term
|
Definition
can be rigid (lipid and cholesterol)
Flexible (lipid and surfactant) |
|
|
Term
| Physical enhancement tech |
|
Definition
structure based (microneedle)
electrically based (iontrophoresis, electroporation, ultrasound, photomechanical wave)
Velocity based (jet propulsion) |
|
|
Term
|
Definition
small electric charge applied to drug reservoir on skin surface
same charge electrodes as solute to produce repulsion effect
drives solute into skin
god for small drugs and peptides and proteins
can cause erythema at site
E TRANS system for fentanyl by pressing a button for release
glucowatch measure glucose levels |
|
|
Term
|
Definition
increase diffusion with little effect on partition
uses small frequency 20kHz
little data to data |
|
|
Term
| photomechanical waves (PW) and laser ablation |
|
Definition
PW: possible channel thru stratum corneum
transient permeabilisation effect in skin
laser: ablation of stratum corneum |
|
|
Term
|
Definition
create physical pathway, less that cutaneous nerves
potential for large proteins and peptides-vaccines |
|
|
Term
|
Definition
helium driven particle accelerators
sml and lge molecules like insulin and vaccines
reports of tissue damage but may be alternative to injection |
|
|
