Topical Drug Delivery

What is the stratum corneum?

outermost layer of the skin

What are the parts of the stratum corneum?

-hydrophilic corneocyte

-lipid matrix

What does a topical drug have to pass through to reach the dermis?

-stratum corneum

-hydrophilic corneocyte

-lipid matrix

What are the advantages of topical formulations?

-high drug concentration at application site

-no first pass effect

-low risk of systemic side effects

-non-invasive

-easy to use

-self-administration

-many OTCs

What are the disadvantages of topical formulations?

-poor patient adherence

-limited contact time

-ointments and creams messy

-small amount absorbed systemically

-formulations can cause skin irritation

-sensitization

-specialized packaging system

What are the layers of the skin?

-epidermis

-dermis

-subcutaneous layer

What is apart of the dermis?

-connective tissue

-blood vessels

-nerves

-hair follicles

What are the skin appendages?

-nails

-sweat glands

-sebaceous glands

-hair follicles and hair

What is the surface area of the stratum corneum?

high surface area

What is the surface area of the sweat-pore?

low surface area

What is the surface area of the hair follicle?

low surface area

Where does topical drug absorption occur?

through stratum corneum, not skin appendages

What are bricks in the stratum corneum?

corneocytes in stratum corneum tightly packed, flattened, dead cells with no nucleus

What is the stratum corneum packed with?

fibrous keratin for hardness and strength

What is the function of corneodesmosomes?

hold corneocytes together

What is the mortar of the stratum corneum?

intercellular lipids

What is desquamation?

process by with "brick wall" is maintained at a constant thickness

How long does the turnover of the epidermis take?

21-28 days

What model represents drug absorption across the stratum corneum?

Fick's First Law

What is Fick's First Law?

dM/dt = (DxKxdelta C)/ h

dM/dt - amount/time

D - diffusion coefficient of drug

K - partition coefficient of drug between skin and formulation

delta C - drug concentration gradient

h - thickness of stratum corneum

A - area of skin contact

What are properties of drugs that absorb across the SC by the intercellular route?

-small molecular weight

-moderate lipophilicity

-unionized form

-adequate potency

What is the action of water with the SC?

penetration enhancer

What physiological factors impact topical drug absorption?

-anatomical site

-skin hydration

-pH

-Temperature

-Desquamation

-Burns

-Eczema

How does anatomical site impact topical drug absorption?

eyelids or face are thinner and have faster absorption than palms and soles

How does skin hydration impact topical drug absorption?

-hydrated SC permeable

-sebum acts as a barrier against water loss

-occlusive ointments enhance hydration and absorption

How does pH impact topical drug absorption?

-affects drug ionization

-unionized drug absorbs faster than ionized

How does temperature impact topical drug absorption?

higher temp can increase skin blood flow and drug absorption

How does desquamation impact topical drug absorption?

shedding of stratum corneum can remove drug from skin

How do burns impact topical drug absorption?

loss of SC barrier and increased drug absorption

How does Eczema impact topical drug absorption?

inflamed, damaged skin has reduced barrier function

What is the skin like in neonates(first 4 weeks of life)?

thinner than adult skin

What is the skin like in pre-term infants(28-34 weeks)?

-born before full skin maturation

-potential for drug absorption and systemic toxicity

What are neonates and pre-term infants susceptible to?

infection

What is the goal of local drug delivery?

deliver drugs to the skin to achieve local action while minimizing systemic exposure

What is drug therapy used for with the stratum corneum?

-dry skin

-barrier repair

-moisturizer

What is drug therapy used for with the epidermis?

-bacterial infection

-fungal infection

-acne vulgaris

What is drug therapy used for with the dermis?

-inflammation

-eczema

-psoriasis

What are characteristics of hydrocarbon bases?

-will not absorb water

-emollient

-occlusive

-greasy

-inexpensive, non-reactive, nonirritating

-insoluble in water

-not water-washable

-anhydrous

What are examples of hydrocarbon bases?

-white petrolatum

-white ointment

-vegetable shortening

-vaseline

What are the characteristics of anhydrous bases?

-can absorb water

-emollient

-occlusive

-greasy

-may be sensitizing or sticky(wool)

-may have compatability problems(soap)

-insoluble in water

-not water-washable

-anhydrous

What are examples of anhydrous bases?

-lanolin

-aquaphor

-aquabase

-polysorb

-hydrophilic petrolatum

What are the characteristics of water-removable bases?

-can absorb water

-less emollient

-non-occlusive

-non-greasy

-may have compatability problems

-may dry out

-insoluble in water

-water-washable

-contains water

What are examples of water-removable bases?

-vanishing cream

-dermabase

-velvachol

-unibase

-hydrophilic ointment

What is the use of water-removable bases?

moist, weeping lesions, oozing wounds

What is the appropriate handling of topical formulations?

-wash hands/wear gloves

-clean application area

-apply prescribed amount

What is proper storage of topical formulations?

-avoid heat, light, moisture

-store according to product labeling

-may require refrigeration

-keep containers tightly closed

What is safety with topical formulations?

-keep out of reach of children and pets

-do not apply heat over treated area

-avoid plastic wrap and tight bandages