540 Exam 3 - Topical/transdermal I

Front 1

Characteristics of oral delivery

Back 1

Blood interface: indirect
Delivery Issues: 1st pass metab
Convenience: High
Onset of action: Slow
Micromolecular delivery: no
Bioavailability: low to high
Dose control: Moderate
vs. pulmonary delivery: Slower onset,

Front 2

Characteristics of IV delivery

Back 2

Blood interface: direct
Delivery Issues: supervised administration
Convenience: low
Onset of action: rapid
Micromolecular delivery: yes
Bioavailability: ref. standard
Dose control: good
vs. pulmonary delivery: costly, inconvenient

Front 3

Characteristics of IM/SC delivery

Back 3

Blood interface: indirect
Delivery Issues: painful injection
Convenience: low
Onset of action: moderate
Micromolecular delivery: yes
Bioavailability: moderate to high
Dose control: moderate
vs. pulmonary delivery: painful, inconvenient

Front 4

Characteristics of transdermal delivery

Back 4

Blood interface: indirect
Delivery Issues: More variable, lowered delivery
Convenience: Moderate
Onset of action: slow
Micromolecular delivery: no
Bioavailability: low
Dose control: poor
vs. pulmonary delivery: slow onset, variable uptake

Front 5

Characteristics of pulmonary delivery

Back 5

Blood interface: indirect
Delivery Issues: deep/slow inhalation
Convenience: moderate to high
Onset of action: moderate to rapid
Micromolecular delivery: yes
Bioavailability: moderate to high
Dose control: moderate to good
vs. pulmonary delivery: rapid onset

Front 6

2 types of dermal drug delivery

Back 6

topical (ointments, creams)
systemic (dermal patches)

Front 7

Problems with surface epithelium and appendages

Back 7

Dry skin and surface infections

Front 8

Problems with lower epidermis, dermis

Back 8

Infections and inflammation

Front 9

Functions of the skin

Back 9

Thermoregulation
Barrier to pathogens and foreign chemicals
Protection against water loss, physical abrasion, and UV radiation.

Front 10

Five layers of epidermis

Back 10

(CLGSB)
Stratum corneum
Stratum lucidum
Stratum granulosum
Stratum spinosum
Stratum germinativum/basale

Front 11

Makeup of stratum corneum

Back 11

-Most important barrier water and other molecules.
-Made up of keratin layer, glycine and alanine, disulfide bonds.
-10 um thick
-Blocks of keratin embedded in extracellular lipids
-Flattened, dead cells (no nucleus)
-Extracellular lipids arranged into bilayers that form sheets.

Front 12

Characteristics of epidermis

Back 12

-Avascular
-Turnover is approximately 21-28 days (highest on scalp, low on toes)
-Average thickness: 100 um
-Needs at least 10% moisture to be soft and supple.

Front 13

Characteristics of dermis

Back 13

-Rich blood supply, lymph vessels, and nerve endings, sweat glands, and origin of hair follicles
-Quick diffusion of drugs
-Collagen makes up 70%
-Elastin is loosely arranged and gives elasticity

Front 14

Cells types in the dermis

Back 14

(MFLS)
-Mast cells
-Fibroblasts (synthesis of collagen and elastin)
-Langerhans cells (allergic responses)
-Schwann cells

Front 15

Skin appendages

Back 15

-Occupy 0.1% of total skin surface
(AHSSN)
-arector pili muscle
-hair follicles
-sebaceous glands
-sweat glands
-nail plates

Front 16

Sebaceous glands

Back 16

-Associated with hair follicles
-Hormonal dependent gland (testosterone) so increase in activity at puberty
-Discharge sebum

Front 17

Functions of sebum (essentially an oil)

Back 17

-Protect against penetration of foreign chemicals
-Antibact and fungicidal; fatty acid esters (pH = 5)
-Prevent water loss
-Lubricant, providing slip

Front 18

Role of commercial dry skin products

Back 18

Mimic sebum and help make a barrier against water loss

Front 19

Eccrine glands (sweat glands)

Back 19

-Respond to both thermal and CNS stimulation
-All over body
-Sweat contains lactic acid

Front 20

Apocrine glands (hormone glands)

Back 20

-Do not appear until puberty
-Milky, fatty secretion
-Development of body odor (bacterial decomposition of sweat- acid and cell debris)
-Highest numbers in armpits (axillae)
-Relatively small numbers in underarm, abdomen, gentio-anal area

Front 21

Melanocytes

Back 21

Synthesize and distribute melanin which absorbs UV light and protects skin. Located in basale layer (epidermis-dermis interface) and make up every 4th cell.

Front 22

Langerhan cells

Back 22

Responsible for uptake and processing of antigenic material

Front 23

Pathways of drug permeation through skin

Back 23

-Transcellular (across cell membrane)
-Paracellular (between cells/intercellular junctions)
-Transappendageal (hair follicles and glands)

Front 24

Diffusivities of water through stratum corneum

Back 24

(cm) = 4 x 10^-3
Dm (cm2/sec) = 4.2 x 10^-10

Front 25

Diffusivities of water through dermis

Back 25

(cm) = 2 x 10^-2
Dm (cm2/sec) = 2 x 10^-6

Front 26

Diffusivities of water through erythrocyte membrane

Back 26

(cm) = 5 x 10^-7
Dm (cm2/sec) = 6.5 x 10^-9

Front 27

Diffusivities of water through leucocyte membrane

Back 27

(cm) = 1 x 10^-6
Dm (cm2/sec) = 2.8 x 10^-9

Front 28

Fick's first last of diffusion for drug transport across stratum corneum

Back 28

dM/dt = (D K A DeltaC) / h

dM/dt = steady state flux across stratum corneum
D = diffusion coefficient or diffusivity of drug molecules
deltaC = drug conc gradient across stratum corneum
h = thickness of stratum corneum

Front 29

Simple diffusion: flux

Back 29

Js = (Dm*Km*deltaC)/h

Js = flux
Dm = diffusion coefficient of drug in skin
delta C = conc dfference inside and outside skin
h = membrane thickness

Front 30

Simple diffusion: Pm (permeability coefficeint)

Back 30

Pm = (Dm*Km)/h

Pm = permeability coefficient
Dm= diffusion coefficient of drug in skin
h = membrane thickness

Front 31

Absorption of drug is affected by (five things)

Back 31

1. Cs, conc of drug in vehicle
2. h, thickness of barrier (skin)
3. D, mobility of drug molecule in barrier
4. K, relative solubility of drug
5. A, contact surface area of vehicle

Front 32

Rules for diffusion through the skin for hydrophobic vs. hydrophilic molecules

Back 32

1. Small hydrophilic, polar molecules are rate controlled by the stratum corneum.
2. Small hydrophobic molecules are controlled by partitioning from stratum corneum into lower epidermal layers.

Front 33

Rules for diffusion through skin: molecular size

Back 33

Diffusion decreases with increasing molecular size.

Front 34

Rules for diffusion through skin: occlusion of skin and damage of stratum corneum

Back 34

1. Occluding the skin increases hydration of stratum corneum and increases permeability.
2. Damage destroys barrier properties of stratum corneum.

Front 35

Physiological factors affecting transdermal bioavailability

Back 35

-stratum corneum
-anatomic site
-skin metabolism (CYP 450)
-skin hydration
-age: premature neonates
-desquamation or shedding

Front 36

Formulation factors affecting bioavailability

Back 36

-O/W partition coefficient of drug
-size and charge of drug
-contact time
-drug conc
-active surface area of transdermal system
-penetration enhances (surfactants)

Front 37

Relative amount drug permeated on sites (mg/cm2)

Back 37

Highest to lowest:
-post auricular
-back
-chest
-stomach
-forearm
-thigh

Front 38

Effects of hydration (water) on diffusion

Back 38

Fully hydrated skin has more loosely "packed" hydrocarbons so it is more fluid and permeable. This facilitates the diffusion of drug molecules.

Front 39

Maximizing Transdermal Drug Delivery: Passive, diffusion methods to modify SC

Back 39

hydration, chemical enhancers, thermal passive

Front 40

Maximizing Transdermal Drug Delivery: SC poration methods: mechanical

Back 40

microstructure array, SC removal, high velocity particles, liquids

Front 41

Maximizing Transdermal Drug Delivery: SC poration methods: elctronically driven

Back 41

sonophoresis, ionophoresis, electroporation, thermal poration, radio frequency poration