Exam 3 - Topical & Transdermal Drug Delivery

Question 1

Describe the living (viable) epidermis

Answer 1

• the layer of skin directly below the stratum corneum
• living cells without capillaries, cells get nutrition by diffusion from dermis
• source of skin color and tanning

Question 2

Describe the dermis

Answer 2

• the layer of skin below the living epidermis
• contains capillaries
• drug needs to reach these capillaries to achieve systematic action (so the drug can achieve an effect)
• contains pain, thermal, and tactile sensors
• injury must reach dermis to produce scarring

Question 3

Describe the importance of hair follicles to drug delivery

Answer 3

• secondary route of drug absorption that bypasses the stratum corneum
• typically used to treat acne and other conditions

Question 4

Describe the stratum corneum (“horny layer”)

Answer 4

• main barrier to permeation
• made up of dead cells & lipids
• the dead skin cells are NOT permeable
• functions as a lipid barrier
• state of hydration is directly related to the ease of permeation

Question 5

Explain the brick & mortar model

Answer 5

• referring to the makeup of the stratum corneum
• bricks = dead cells
• mortar = lipids
• permeation occurs by partitioning through the lipid material (mortar) between the dead cells (bricks)

Question 6

List the general functions of the skin

Answer 6

• containment
• microbial barrier
• chemical barrier
• radiation barrier
• electrical barrier
• thermal barrier & body temp regulation

Question 7

Explain the skin’s function “containment”

Answer 7

confine underlying tissues and restrain their movement

Question 8

Explain the skin’s function as a microbial barrier

Answer 8

• pH of skin = 5 - inhibits growth of bacteria
• sebum contains bacteriostatic and fungistatic fatty acids (propanol, butanoic, hexanoic, and heptagons acids)

Question 9

Explain the skin’s function as a chemical barrier

Answer 9

permeability resistance of stratum corneum is several orders of magnitude greater than other barrier membranes of the body

Question 10

Explain the skin’s function as a radiation barrier

Answer 10

exposure to the UV stimulates synthesis of melanin, which absorbs UV rays

Question 11

Explain the skin’s function as an electrical barrier

Answer 11

• offers high impedance to the flow of an electrical current
• need to treat the skin with salt solutions and overcome the impedance to measure body potentials (electroencephalograms or electrocardiograms) – use granular salt suspensions, creams, pastes containing electrolytes

Question 12

Explain the skin’s function as a thermal barrier

Answer 12

maintains 98.6F (37℃) by dilating/contracting blood vessels or sweating

body temperature regulation

Question 13

Why do we use topical drug delivery?

Answer 13

only skin, no systematic side effects → stays at the site of application, LOCAL effects

Question 14

Define “keratolysis”

Answer 14

chemical digestion and removal of horny tissues

Question 15

Explain the effects of antiperspirants on the skin’s glands

Answer 15

irritate and close the orifice eccrine glands to impede sweat flow
(aluminum chloride)

Question 16

Give examples of acne products that work on the skin’s glands

Answer 16

soap, alcoholic solutions, antibiotics, retinoids

Question 17

Describe the effects of retinoids used for acne

Answer 17

reset the processes of epidermal proliferation and differentiation, which prevents the formation of lesions

Question 18

Name the most hydrophobic ointment bases

Answer 18

hydrogen based

ex. petrolatum, polyethylene dissolved in mineral oil (plastibase)

Question 19

Name the most hydrophilic ointment bases

Answer 19

water soluble bases

ex. polyethylene glycol ointment

Question 20

Describe absorption bases

Answer 20

ointment containing w/o emulsifiers

ex. w/o emulsions containing aqueous solution of a drug

Question 21

What do silicon bases contain?

Answer 21

polymethylsiloxane oil

Question 22

Define “pastes”

Answer 22

ointments that are highly concentrated of insoluble particulate solid

Question 23

Define “creams”

Answer 23

o/w or w/o emulsions

Question 24

Define “gels”

Answer 24

liquid phase trapped in matrix of a natural or synthetic polymer (tragacanth, pectin, carrageenan, methyl cellulose, carbopol)

ex. topical scalp gels (not too greasy)

Question 25

Define "rigid foams"

Answer 25

air or other emulsified in a liquid phase (ex: whipped cream) **liquid phase may contain a drug** ex. aerosol shaving creams, medicated quick-breaking antiseptic foams

Question 26

List examples of topical / transdermal medications that produce effects in deep tissues

Answer 26

- topical corticosteroids - NSAIDs: diclofenac - local anesthetics: benzocaine - lightened excessively pigmented skin: hydroquinone - skin cancer: 5-fluorouracil

Question 27

Describe the location of effects transdermal drug delivery

Answer 27

- skin is the route of entry, but the effects are elsewhere - systemic drug delivery (via bloodstream)

Question 28

List the requirements for drugs delivered transdermally

Answer 28

SMALL & LIPOPHILIC - must reach dermal capillaries - of particular interest for drugs that have a short systemic half-life (helps prevent need for frequent dosing)

Question 29

Name an advantage of transdermal drug delivery, specifically patches

Answer 29

patches are beneficial because you can take off when no longer need AND for patients who do not like needles

Question 30

When is transdermal delivery NOT the best option?

Answer 30

if a patient needs a lot of a drug

Question 31

Transdermal drug delivery works best with drugs with what specific characteristics?

Answer 31

- Low molecular weight (<1000 Da) - Moderate lipophilicity (log P ~1-4) - Potency (low dose requirement = highly potent)

Question 32

What is one important counseling point for patients using transdermal patches?

Answer 32

Must remember to rotate sites

Question 33

Describe dissolving microneedles

Answer 33

type of polymeric MN that can degrade or dissolve post insertion into the skin, leading to the delivery of the encapsulation drug at site of application **on transdermal patches**

Question 34

Describe hydrogel forming microneedles

Answer 34

have cross-linked hydrogel structure that can collect interstitial fluid upon skin application → in-site hydrogen

Question 35

List types of microneedles used on transdermal patches

Answer 35

- dissolving microneedles - hydrogel forming microneedles - separable microneedles - hollow microneedles

Question 36

Describe separable microneedles

Answer 36

rapidly dissolvable backing layers; with weaker connection between the backing layers and the MN tips; or based on a hydrogel backing layer

Question 37

Describe hollow microneedles

Answer 37

each needle incorporates a hollow cavity within and a bore on the needle tips, to which small volumes of drug solutions can be injected needle is hollow and gets into the skin

Question 38

Explain the purpose of enhancers

Answer 38

to make the skin more permeable for transdermal patches (rotate sites, or else the site will weaken)

Question 39

List types of enhancers

Answer 39

- ionic surfactants - ascorbate, dithiothreitol - azone - dimethyl sulfoxide (DSMO)

Question 40

Describe the mechanism of ionic surfactants as enhancers

Answer 40

disorder the lipid layer of stratum corneum to sweep and/or leach out some of the structural components, thus reducing the diffusional resistance

Question 41

Describe the mechanism of ascorbate & dithiothreitol as enhancers

Answer 41

- reducing agents - disrupt disulfide bonds of proteins in keratinized cells

Question 42

Describe the mechanism of azone as an enhancer

Answer 42

- nonpolar, oily liquid - has effects in the lipid bilayer - targets lipid lamella region (middle of the lipid layers of cells) - best for lipophilic cells - mechanism: fluidizes lipids

Question 43

Describe the mechanism of dimethyl sulfoxide (DSMO) as an enhancer

Answer 43

- dipolar solvent. - targets aqueous region of lipid bilayer best for hydrophobic drugs/small molecules - mechanism: expands polar head spacing

Question 44

Given examples of drugs delivered via membrane-modulated transdermal delivery

Answer 44

Scopolamine (Transderm-Scop) Nitroglycerin (Transderm-Nitro)

Question 45

Given examples of drugs delivered via matrix dispersion transdermal delivery

Answer 45

Nitroglycerin (Deponit)

Question 46

Given examples of drugs delivered via adhesive dispersion transdermal delivery

Answer 46

Nitroglycerin (Nitrodur)

Question 47

List examples of drugs that are commonly delivered transdermally

Answer 47

- nicotine - clonidine - nitroglycerin - estradiol - scopolamine - fentanyl

Question 48

Describe transdermal nitroglycerin (t1/2, indication)

Answer 48

half-life: 3 mins (short half-life) indication: prevention of angina pectoris (chest pain) due to coronary disease; not for immediate relief of acute attacks

Question 49

Describe transdermal rivastigmine (indication, solubility)

Answer 49

indicated for memory problems (dementia) associated with Alzheimer’s disease or Parkinson’s disease solubility: sparingly soluble in water very soluble in ethanol, acetonitrile, n-octagon, ethyl acetate

Question 50

Describe transdermal contraceptive (dosage, system type)

Answer 50

150 mcg/day norelgestromin and 35 mcg/day ethinyl estradiol matrix-type transdermal system: backing layer - structural support middle layer - adhesive, matrix & drug 3rd layer - protective layer (removed)

Question 51

List factors affecting drug permeability through skin

Answer 51

- hydration - solubility of drug in stratum corneum - excipients (solvents, surfactants) - pH (drug ionization state)

Question 52

Explain how hydration affects drug permeability through the skin

Answer 52

- the more hydrated, the greater the drug permeability (and the more the swollen the drug) - water associated with polar head groups of lipid bilayer loosens the lipid packing and make the bilayer more fluid

Question 53

What is the human growth hormone (hGH)

Answer 53

a PROTEIN **does not easily cross the skin barrier**

Question 54

List the methods of penetration enhancement

Answer 54

- iontophoresis - electroporation - ultrasound - prodrugs - (chemical) penetration enhancers

Question 55

Describe iontophoresis

Answer 55

uses low voltage electrical current to drive charged drugs through the skin

Question 56

Describe electroporation

Answer 56

uses high voltage (short) to create transient pores in the skin **early stage, but very good**

Question 57

Describe ultrasound

Answer 57

uses low frequency ultrasonic energy to disrupt the stratum corneum

Question 58

Describe prodrugs

Answer 58

make the skin lipophilic (make more hydrophobic)

Question 59

Give examples of (chemical) penetration enhancers

Answer 59

alcohol, dimethyl sulfoxide (DSMO), surfactants, acetone, ethyl acetate

Question 60

List potential mistakes that can be made in the preparation stage of using transdermal patches

Answer 60

- removal of the patch from the packaging - removal of the protective foil - alternation of the patch

Question 61

List potential mistakes that can be made in the removal stage of using transdermal patches

Answer 61

correct frequencies for application: - daily (e.g. nicotine, rivastigmine) - bid (e.g. diclofenac) - twice weekly - weekly (e.g. buprenorphine, clonidine, estradiol) - q72h (e.g fentanyl)

Question 62

List potential mistakes that can be made in the application stage of using transdermal patches

Answer 62

- recommended that the patch goes in an area of skin with no hair and to rotate sites - the correct common application site

Question 63

List potential mistakes that can be made in the monitoring stage of using transdermal patches

Answer 63

influence of heat patch displacement