ceutics transdermal 1

transdermal drug delivery is a discrete dosage form which when applied to INTACT skin will deliver the drug at a ________ rate to _____________

controlled rate; systemic circulation

transdermal drug delivery advanatges

First pass metabolism avoided

Frequency of dosing reduced

Controlled delivery (reliable blood levels)

Compliance

Termination is possible

Self medication

"facts"

transdermal drug delivery maintains therapeutic levels for _________ days

1-7 days

for transdermal devices, a daily dose of more than _____mg may not be possible

20mg

t/f: drugs requiring high blood levels are unsuitable for transdermal devices

true

drugs with a _______ half life can not be formulated for transdermal devices

long

characteristics of drugs not suitable for transdermals

1. greater than 20mg

2. if needed in high blood levels

3. long half life drugs

4. high molecular weight compounds

drugs that are continuously infused into the skin (aka transdermals) must have a _________ half life

short

t/f: TDD is usually reserved for drugs that are extremely potent

true (thus requiring less mg)

the largest daily dose of a drug from a patch is

21 mg nicotine patch

5 layers of epidermis

1. stratum corneum (horny cell)

2. stratum lucidum (clear)

3. stratum granulosum (granular)

4. stratum spinosum (prickly)

5. stratum germinativum

Come Lets Get Some Grub

which 3 layers of the epidermis are the "thicker parts" and result in increased permeability if removed

lucidum, granulosum, spinosum (middle 3)

describe thickness of stratum corneum and what chemical bonds are present

10-15 micrometers thick

-keratin (cysteine disulfide bridges)

-glycine and alanine (H bonds)

*primary permeability barrier

describe the model used for the stratum corneum

"brick and mortar model"

brick= squamous cells of corneum

mortar= lipid matrix

while the stratum corneum is made up of keratin, the dermis is made of _______

collagen

what is responsible for skin elasticity

COLLAGEN fibers in DERMIS with uniform thickness

t/f: the dermis is supplied by blood

true. it is supplied by blood to provide nutrients, remove waste, and regulate body temp

in which region of the skin is drug well absorbed and why

the dermis; it is supplied by blood

subcutaneous tissue: location? histology?

fat with areolar tissue; attaches dermis to underlying structure (hypodermis)

describe sweat gland characteristics and function

sweat pH 4-6.8

absorbs drugs, secretes proteins, lipids, antibodies

fcn: control heat

hair follicles have _______ glands which produce _____ containing glycerides, cholesterol, and squalene

sebaceous glands; sebum

what mechanism regulates transdermal absorption

diffusion-> fick's law

3 routes of drug absorption through skin

1. trans follicular= hair/shunt

2. trans epidermal= intracellular

3. intercellular = between cells [highest amount]

which route of percutaneous drug absorption is most prevalent

intercellular= between cells through lipid matrix

(for lipophilic drugs)

which drugs prefer the trans follicular route

water-soluble drugs

describe how hydrophilic drugs diffuse through skin

prefer transfollicular route

- sweat glands and hair acts as shunt

- diffuses through rate limiting ST corneum

t/f: residence time of drug in the dermal layer is short, less than a minute

true. dermal layer has many capillaries, promoting drug absorption

describe how prodrugs enhance transdermal drug delivery

- promoiety increases partition coefficient and solubility

=> transport through stratum corneum

-epidermis: esterases release active drug

pro moieties increase __________ of a drug

partition coefficient and solubility (to get pass s. corneum)

where is a prodrug "released"

epidermis via esterases

factors affecting transdermal permeability

1. API= solubility, pH, concentration

2. DDS= release, excipients, permeation enhancer

3. skin= lipid film, skin hydration, temp, injury

4. biological= skin age, s. corneum thickness, skin condition

which layer of skin has greatest influence on transfer of drug from vehicle to skin

s. corneum

t/f: solubility of drug influences its ability to penetrate the skin

true

__________ determines drug concentration presented to absorption site

drug solubility

skin permeation can be enhanced by increasing the ____hydrophilic or lipophilic?___ character of drug

lipophilic (so that it penetrates s. corneum but not epidermis)

t/f: drug which is both lipid and water soluble is favored for transdermal DDS

true

what pH is favorable for skin absorption

moderate pH (too low or too high can destroy skin)

compare concentration vs solubility levels to produce a drug reservoir

at higher concentrations than solubility, excess solid drug will act as reservoir

_________ of drug in vehicle determines release rate

solubility

which compound would be more absorbed by the skin: methyl salicylate (ph= 7.5) or salicylic acid (ph 2.4)

methyl salicylate as it is unionized and more LIPOPHILIC= more absorption

removal of skin's lipid film would _______ TD absorption

decrease

something that dehydrates the skin would ___________ drug absorption

decrease

how does skin age affect absorption

children and elders= more permeable

adults= less permeable

which layer of skin is metabolically active

epidermis

4 components of transdermal DDS

1. polymer matrix

2. drug

3. permeation enhancer

4. excipients

criteria for selecting polymer for TDDS

1. molecular weight allows drug diffusion

2. non-reactive, inert, non-toxic, inexpensive polymer

3. not decompose over time or w drug

examples of polymers used in TDDS

cellulose derivs, gelatin, gums, rubber, PVC, PVP, poly etc.

properties of drug chosen for TDDS

1. weigh less than 1000 daltons

2. both lipophilic and hydrophilic

3. LOW melting point (easy to be liquid)

4. POTENT (few mg/day)

5. short half life

6. non irritating

How do penetration enhancers work?

1. interact with polar head groups (hydrogen/ionic bonding)

2. provide moisture/ increase hydration

3. protein modification= open up dense keratin

describe characteristics of backing membrane of transdermal DDS

1. impermeable membrane, protects product

2. compatible with formulation (non adsorptive)

3. flexible, good bond to drug reservoir

examples of backing membrane of TDDS

metallic plastic laminate, plastic backing with adsorbent pad adhesive foam pad

t/f: drugs in TDDS can be liquid, semi-solid, or non-flowing

true

types of TDDS platforms

1. monolith: slabs, reservoir, film, reservoir matrix

2. films: natural vs synthetic, porous vs nonporous

3. adhesives: permanently tacky

TDDS adhesive must be permanently "tacky". what does this mean

sticks to skin without any pressure

what are the 5 types of transdermal control release systems

1. polymer membrane permeation

2. polymer matrix diffusion

3. adhesive dispersion

4. gradient controlled

5. microreservoir/microsealed

polymer membrane permeation system:

-describe makeup

-counseling

-example

1. drug in reservoir + rate controlling polymer membrane + adhesive layer

2. break in membrane= dose dumping

3. ex: nitroglycerin

which TDDS could potentially have dose dumping

polymer membrane permeation controlled system

Adhesive dispersion type system:

- makeup?

- examples

1. drug directly dispersed in adhesive layer

-adhesive polymer: polyisobutylene and polyacrylet

2. ex: isosorbide dinitrate, verapamil

gradient controlled TDDS

3 gradient layers with drug reservoirs-> diffuses down into skin

ex: nitroglycerin

polymer matrix diffusion controlled TDDS

-drug dispersed homogenously in polymer matrix; in contact with skin (adhesive rim)

ex: nitro-dur 1 and 2

Microreservoir/microsealed dissolution controlled TDDS

a. MOST STABLE DEVICE

b. NO DOSE DUMPING

c. Drug dispersed first in water soluble polymer and then lipid soluble polymer= forms microscopic spheres of drug reservoir

d. Cross linking= constant SA and fixed thickness

e. Ex: nitro-disc

f. ZERO ORDER

which TDDS is most stable

microreservoir/microsealed dissolution controlled

which TDDS is controlled by a drug getting past a nonporous or porous membrane

polymer membrane permeation controlled system

which TDDS has a drug dispersed in a matrix in contact with the skin

polymer matrix diffusion system

which TDDS follows zero order kinetics and involved dissolution

Microreservoir/microsealed dissolution