Transdermal Drug Delivery System

systemic circulation

transdermal administration targets ____________________ by diffusion through the skin

epidermis

layer of the skin that is the must superficial; composed of two major layers: the stratum corneum and the viable epidermis

keritonocytes

the live cells of the epidermis that get pushed up

50-100

the viable epidermis is ____________ mcm thick

10-20

the stratum corneum is ____________ mcm thick

corneocytes

dead keratinocytes that make up the stratum corneum

stratum corneum

the rate-limiting step of transdermal drug absorption is passive diffusion through the cornified layer of the _______________________

dermis

the blood vessels in the skin are in the ______________ (where the drug molecules need to get to)

percutaneous

route of administration involving the skin: either topical for direct local applications (cream/ointment) or transdermal application for systemic effects

skin, tissues

molecules have three potential pathways to get from the ______ surface to the viable ___________:

1) through sweat ducts

2) via hair follicles

3) across the intact stratum corneum enclosing them

hydrophobic

____________ drugs are more ideal for transdermal administration because they can pass through the lipid bilayer of the cells

hydrophilic

_______________ drugs are not ideal for transdermal application because they have to pass through proteins

percutaneous absorption mechanism

1) partitioning of the drug from the vehicle into the stratum corneum

2) molecular diffusion through the stratum corneum

3) partitioning from the stratum corneum into the viable epidermis

4)diffusion through the epidermis and capillary uptake

high

lipophilic drugs have a ________________ partition coeffeicient

low

hydrophilic drugs have a _______________ partition coefficient

advantages

_________________ of transdermal administration

-permits self-administration

-allows removal of drug source

-non-invasive

-improves patient compliance

-sustains therapeutic drug levels

-reduces first-pass effect and GI incompatibility

disadvantages

_____________ of transdermal administration

-poor diffusion of large and hydrophilic molecules

-skin irritation

topical

for ____________ application, a large dose must be applied because bioavailability is so low (1-3%)

reservoir system

type of transdermal delivery system in which the active drug is stored in a special patch compartment and released through a rate controlling membrane. The drug concentration gradient across a constant thickness polymer membrane is essentially invariant with time and thus constant release rate

matrix system

type of transdermal delivery system in which the drug is released from a polymer matrix onto the skin where the rate of delivery is dependent on the rate of diffusion through the skin. The concentration gradient is time dependent and decreases progressively in response to the time growing thickness of diffusion

vapour patch

type of transdermal delivery system used in cases of decongestion, improving quality of sleep, and reduces quantity of cigarettes smoked. Release essential oils for up to 6 hours

can

matrix type patches _________ be cut in half

cannot

reservoir type patches __________ be cut in half

first

_____ generation TDDS that includes traditional patches such as clonidine or estrogen

second

_______ generation TDDS include patches plus some type of enhancement to improve drug delivery

third

________ generation TDDS use novel technologies to increase the scope of molecules that can be delivered through the skin

low

ideal drugs for transdermal application should have __________ molecular weight

daily

ideal drugs for transdermal application should have ________ doses

short

ideal drugs for transdermal application should have a _________ half life (10 hours or less - anything longer can be used for oral admin)

200

ideal drugs for transdermal application should have a melting point less than _________ Celsius

C1

Fick's law variable that is the drug concentration of the formulation

C2

Fick's law variable that is the drug concentration in the skin/circulation

Kp

Fick's law variable for partition coefficient

h

Fick's law fariable for thickness of the epidermis

D

Fick's law variable that is the diffusion coefficient

enhancement

_______________ techniques for transdermal drug delivery include prodrugs and ion pairs, use of solvent carriers/vehicles, supersaturated drug solutions, and chemical enhancers acting on the structure of the stratum corneum lipids and keratin

iontophoresis

physical method for enhancement techniques that use electromotive drug administration (EMDA); apply low level electrical current to move charged and uncharged species across the skin - useful for hydrophilic molecules

electrophoresis and electroosmosis

mechanism for iontophoresis

same

the charge of the anode of an iontophoretic patch and the charge of the drug must be ______________

electroportaion

physical method for enhancement techniques that applies short, high voltage electric pulses; safe and painless; allows cellular introduction of large, highly charged molecules across the hydrophobic bilayer core

sonophoresis

acoustical method for an enhancement technique; uses ultrasound energy at a high frequency.

Mechanism:

-increased fluidity in the lipid bilayer

-cavitation or the formation of small gas bubbles

-thermal effects (temperature increase)

microneedles

enhancement technique in which micron dimension needles pierce skin surface to create holes that are large enough for molecule entrance but small enough to avoid pain; used to administer proteins, vaccines, and larger molecules

enhancement

_____________ techniques:

-transdermal diffusion by chemical enhancers

-low-voltage electrical enhancement by iontophoresis

-high-voltage enhancement by electroporation

-microneedles