Part 4 - Transdermal Drug Delivery Systems Flashcards
there are many different dosage forms available via the skin route.
name those that give SYSTEMIC effects and those that give LOCAL effects
systemic effects - transdermal patch
local- ointments, creams, lotions, topical solutions, pastes, liniments, powders, gels, tinctures, aerosols
what is percutaneous absorption?
the absorption of substances from outside the skin to positions beneath the skin (including entrance to the bloodstream)
remember: per in Latin means THROUGH
give the components of the stratum corneum of the skin
protein, water, lipid
40% protein (keratin)
40% water
20% lipid (triglycerides, free fatty acids, cholesterol, phospholipids)
name the types of skin penetration that can occur with a drug
-transcellular penetration
-intercellular penetration
-transappendageal penetration
differentiate between the types of skin penetration by a drug
transcellular = across cells. PASSIVE. no enzymes needed
intercellular - between cells. again - no energy or enzymes needed
transappendageal - penetration via hair follicles, sweat/sebum glands, and pilosebaceous apparatus
between the 3 types of skin penetration by a drug, which is the most common absorption mechanism?
intercellular penetration
paracellular penetration is also known as….
intercellular penetration
put the following in order from superficial to deep:
dermis
stratum corneum
epidermis
statrum corneum
epidermis
dermis
of the 3 penetration mechanisms, which does not happen naturally?
transappendageal penetration.
physically pushed through a hole (hair follicle, sweat/sebum gland, pilosebaceuos apparatus)
name 5 factors that affect percutaneous absorption
-drug
-area of application
-physiochemical attraction to the skin compared to the vehicle
-hydration of the skin
-medicated application period
explain how the drug itself is a factor that affects percutaneous absorption
the concentration – high concentration will mean fast absorption (Fick’s law)
liphophilic drugs penetrate better
ionization reduces penetration (PKA IS IMPORTANT)
small molecules (100-800MW) penetrate faster
for a transdermal patch, what is the ideal molecular weight for the drug? why?
400
MW 100-800 can penetrate
true or false
hydrophilic drugs undergo faster percutaneous absorption
FALSE - lipophilic
Explain how pka value of a drug affects percutaneous absorption
ionization will reduce penetration. therefore, we want to control the pH so the drug remains unionized
what is the thinnest area to apply a transdermal patch and thus has the quickest sbsorption
skin behind the ear
explain how the area of application of the drug on the skin is useful
can help to control the dose.
normally, all patches are the same dose. therefore, to increase the dose you would increase the area of application by applying 2 patches instead of 1
non polar or polar:
which drug will go the transcellular route? what about intercellular?
nonpolar drugs will go the transcellular route (if small)
and polar drugs will go the intercellular route
(unionized, but has polar functional groups)
what is the ideal partition coefficient for percutaneous absorption
1
good for solubility and for permeability
what kind of drug will go through the transcellular pathway of percutaneous absorption
only drugs that are lipophilic and small
true or false
all percutaneous absorption mechanisms are passive
FALSE - transcellular and intercellular are, but not transappendageal
which is more hydrophilic - the epidermis or the stratum corneum?
epidermis
explain the difference between absorption through the GI tract and absorption through the skin
for the GI, the drug first has to dissolve in aqueous phase and then partition through lipid phase
it is the opposite for skin absorption because the epidermis comes after the stratum corneum and the stratum corneum is more lipophilic
how can penetration through the skin be enhanced?
through use of a chemical enhancer to disrupt the phospholipids and make it easier for the drug to get through the stratum corneum
also, absorption can be enhanced through hydration of the skin
true or false
the drug should have a greater physiochemical attraction to the skin than to the vehicle
TRUE – so that the drug will leave the vehicle
what is the “horny layer”?
how does it affect drug absorption through the skin?
stratum corneum
the thinner the stratum corneum, the greater percutaneous absorption
name 7 physiological conditions of the skin that may have an impact on the penetration of the drug
bonding
sebum
hydration
thickness
injury
metabolism
temperature
explain how “bonding” is a physiological condition of the skin that may have an impact on the penetration of the drug
the accumulation of bonding in the epidermis can decrease the initial transport of the drug
explain how sebum in the skin can affect the penetration of the drug through the skin
can alter the pH, and the amount and composition of sebum can alter the passage of the drug
true or false
increased hydration usually decreases penetration rate
FALSE - usually increases
what can increase hydration?
occlusive dressings
how can hydration vary across the skin
the age of the skin
the location of the skin
the condition of the skin
where on our body is the skin very thin?
where very thin?
what does this say about the absorption rate?
thin = behind ear
thick = palm of hand
follows Fick’s first law - very small thickness = easier absorption
explain how injury affects drug absorption through the skin
skin that is cut increases the penetration rate, but applying a transdermal patch may cause irritation and should be avoided
explain how metabolism can affect percutaneous drug absorption
1st pass effects used to be thought to be that drugs were destroyed at the FIRST ENCOUNTER to the body. however, this is not true anymore
we don’t normall have a lot of enzymes hanging around near our skin - they’re in the liver.
in theory tho, increased metabolism causes reduced penetration of the drug
name 2 factors that affect metabolism (skin)
-age
-skin condition
what is the normal temperature of our skin?
~30 degrees celsius
name 3 percutaneous absorption enhancers
-chemical enhancers
-iontophoresis
-sonophoresis
explain how chemical enhancers enhance percutaneous absorption
the increase the skin permeability by REVERSIBLY damaging or altering the physiochemical nature of the stratum corneum. reduces its resistance to diffusion
they cause hydration of the skin and the structure of the lipids and lipoproteins in the intercellular channels are altered
name 3 chemical enhancers
alcohol
azone
DMSO (dimethyl sulfur oxide)
explain how azone and DMSO differ in their functions as chemical enhancers
azone gets inserted between lipid bilayers which increases the permeation of the drug through the intercellular pathway
DMSO SOLVATES the polar heads of the phospholipids which expands the aqueous region
differentiate between iontophoresis and sonophoresis.
what are they used for?
used as percutaneous permeation enhancers.
iontophoresis = delivery of a charged chemical compound across the skin membrane by using an ELECTRICAL FIELD
sonophoresis = used at high frequency ultrasound to increase permeation. the sound waves increase the separation between the cells of the stratum corneum
__________ is(are) PHYSICAL method(s) of increasing drug permeation through the skin
iontophoresis and sonophoresis
define the major barrier of the skin
the stratum corneum
what are the percutaneous absorption models?
-in vivo studies (animals)
-in vitro studies (2 layer models of the skin - side by side and up and down models. - follows Fick’s first law)
explain the advantages/benefits of the 2 in vitro percutaneous absorption models available
the “up and down” model poses an issue when air gets to the top and becomes a barrier
the “side by side” model solves this issue
in the side by side absorption model, the dermis faces the ___ compartment and the epidermis faces the _____ compartment
in the up/down absorption model, the dermis faces __ and the epidermis faces ___
dermis faces donor compartment and epidermis faces receptor compartment
epidermis faces down and dermis faces up
which has looser tissue - the epidermis or the stratum corneum
epidermis
“an application of physical-chemical properties to predict absorption expectation through biological membranes”
membrane permeability studies
according to membrane permeability studies…..
Fick’s first law is followed.
as conc of the drug increases, the rate of diffusion also increases
membrane permeability studies used what kind of invitro equipment?
the side by side model (with dermis facing donor compartment and epidermis facing receptor)
an early assessment of the passage of drugs across biological membranes
membrane permeability studies
“passive absorption mechanism”
Fick’s first law
name and differentiate between the 2 transdermal delivery systems
matrix type (monolithic)
membrane type
monolithic system (matrix type) – has a drug matrix layer between the backing and frontal layers
membrane-controlled systems – contains a drug reservoir (or pouch) usually in liquid or gel form, a rate-controlling membrane, and backing, adhesive, and protecting layers
true or false
the membrane system cannot give zero order drug release
FALSE - IT CAN
matrix type cannot
what does zero order mean
the rate does not vary with the increase or decrease of the concentration of the reactants (drug)
what is the 5 layer, bulky, matrix type patch?
Nitro dur
what component of transdermal delivery systems is included to ensure that the drug will only move unidirectionally?
the backing layer
true or false
if the drug is capable of providing an adhesive, an additional adhesive layer is still needed
FALSE – not needed
in the case of matrix type, there is no adhesive layer and the drug itself serves as the adhesive
the drug reservoir for membrane type is a solution or gel.
what about the drug layer in matrix type system?
it is a POLYMER
increased vehicle viscosity in transdermal delivery systems ____ diffusion coefficient
REDUCES
______concentration/solubility of a drug penetrates better in TDDS
high
true or false
lower concentration gradient = better penetration
false
higher concentration gradient = better penetration
which increase penetration – nonaqueous vehicles or aqueous vehicles? in the case of TDDS
nonaqueous vehicles (occlusive)
in the case of TDDS, _ area causes increased absorption
increased area
name 6 design objectives for transdermal delivery systems
-deliver the drug for percutaneous absorption at therapeutic levels at optimal rate
-contain med agents that can release from the system and partition into the stratum corneum
-occlude the skin to ensure ONE WAY FLUX (dc/dt) into the stratum corneum
-have therapeutic advantage over other dosage forms
-not irritate or sensitize the skin
-adhere well to the skin and have the size, appearance, and site placement that encourage acceptance
in order to ensure that the drug can be released from the system and partition into the stratum corneum……..
it must have the necessary physiochemical characteristics
name 8 advantages of transdermal delivery systems **
-avoid GI absorption difficulties
-substitute for oral administration
-avoid first pass effect
-noninvasive and no inconvenience of parenteral therapy
-may be terminated fast
-provide extensive therapy with a single application
-extend the activity of the drugs having short half life
-easily and rapidly used in emergencies
an advantage of TDDS is avoiding GI drug absorption difficulties.
explain this further
-low pH
-enzymatic activity
-drug interaction with food/drink and other oral drugs
an advantage of TDDS’s is that they extend the activity of drugs having a short half life.
explain this further
there is a reservoir of drug in the delivery system and its release is controlled
drugs with ___ half life are not suitable to be formulated as a transdermal patch
long half life
there’s no point. if you already take 1 tablet a day you would still have to apply the patch every day or so
name 6 disadvantages of TDDS
-only potent drugs are suitable
-contact dermatitis at application site
-limited time that they can stay (due to rashes and sensitization)
-variable intra and inter percutaneous absorption efficacy (everyone has different skin)
-bacterial and enzymatic drug metabolism under the patch
-complex tech/high cost
WHY can only relatively potent drugs be suitable candidates for drug delivery?
the skin is impermeable – natural limit of drug entry
true or false
TDDS are cheap and easy to make
false – complex tech needed and expensive
true or false
percutaneous absorption does not vary with the site of application
FALSE - it does vary
TDDS’s should be applied to what kind of skin
clean and dry skin
true or false
skin lotion should be used before applying a transdermal patch
FALSE
has to be intact, original skin.
lotion will impact the drug release from the patch
true or false
transdermal delivery systems should NOT be physically altered by cutting
true
true or false
a transdermal delivery system should always be worn for the full period stated in the product instructions
FALSE – not the case for nitroglycerin bc of tolerance effect
but for all other cases it is true
what should the patient do with a TDDS after they remove it? why?
fold it in half with the adhesives facing each other so it can’t be reused.
after 24 hrs there’s still a lot remaining in the patch. ~20% used after 24 hours
why is skin irritation a major issue for TDDS
lot of excipients and any possible chemical enhancers
name 7 limitations of TDDS
-not for all drugs
-limited time it can be affixed
-variable inter and intra percutaneous absorption efficacy
-skin rashes, sensitization
-bacterial and enzymatic drug metabolism under the patch
-complex tech/ high cost
what drugs can NOT be used in a transdermal patch
if the drug is not potent
sometimes, drugs with a short half life require a loading dose, and transdermal patches can’t deliver this high dose
also kind of useless for drugs with long half lives
of the patches mentioned, which remains on the skin the longest
7 days - transdermal clonidine (Catapres-TTS)
