Topical Preparations for Percutaneous Applications

What is the topmost layer of the epidermis and the main barrier to drug permeation through the skin?

Stratum corneum

What is the "brick" part of the "brick and mortar" model of the stratum corneum?

Keratinocytes

What is the "mortar" part of the "brick and mortar" model of the stratum corneum?

Intercellular lipids

Tight junctions

Mediate cell-to-cell adhesion between the epithelium and endothelium

What are the major transmembrane proteins of tight junctions?

- Occludin

- Claudins

Zonula occludens

Form cytosolic scaffolds that regulate assembly of tight junctions

Which type of melanin produces brown/black colors?

Eumelanin

Which type of melanin produces yellow/red colors?

Phaeomelanin

What is the water content of the skin?

10-25%

What is the pH range of the skin?

4.2-5.6

What impact does a damaged stratum corneum (damaged skin) have on drug absorption?

increases drug absorption

What are the immune cells present in the dermis?

- Macrophages

- Lymphocytes

- Mast cells

What are the 3 mechanisms of skin permeation?

- Transcellular

- Paracellular

- Transappendageal

Transcellular

Across the cells

Paracellular

Between the cells

Transappendageal

Via hair follicles or sebum glands

What are the systemic advantages of semisolid topical preparations?

- Avoid GI variability

- Drug input can be terminated quickly

- Drug levels can be maintained within therapeutic window

What are the local advantages of semisolid topical preparations?

- Forms an occlusive layer

- Emollient action

- High solid content acts as sunblock and absorbs moisture

What is the formulation-related advantage of semisolid topical preparations?

Low water content of ointments enhances drug stability

What are the disadvantages of semisolid topical preparations?

- Systemic administration is limited to only potent drugs

- Stratum corneum severely restricts drug permeation

- Ointments are greasy and cosmetically unacceptable

Protective

Shields exposed skin surface and other membranes from harmful stimuli

What is an example of a protective topical product?

Calamine lotion

Absorbents

Takes in moisture from skin and maintains dry conditions, preventing bacterial growth

What is an example of an absorbent topical product?

Zinc oxide paste

Demulcents

Alleviates irritation from mucus membrane or bruises

What is an example of a demulcent topical product?

Vaseline

Emollients

Oily substances that keep the skin soft and shiny

What is an example of an emollient topical product?

Mineral oil

Astringents

Help coagulate blood, thus assisting in healing wounds and cuts

What are the 2 examples of astringent topical products?

- Alum

- Oatmeal

Counterirritants

Reduce inflammation by producing secondary irritation

What are the 2 examples of counterirritant topical products?

- Menthol

- Camphor

Caustics

Destroy the skin at the applied site

What are the 2 examples of caustic topical products

- Silver nitrate

- Formaldehyde

Keratolytics

Cause peeling of the skin

What are the 5 examples of keratolytic topical products?

- Salicylic acid

- Benzoic acid

- Benzoyl peroxide

- Coal tar

- Sulfur

What topical preparations use radiation barriers?

Sunscreens

What topical preparations use microbial barriers?

Topical anti-infectives

What topical preparations moisturize the stratum corneum?

Emollients

What topical preparations negate antigens and augment chemical barriers?

Poison ivy products

What topical preparations build up moisture and act as a chemical barrier?

Diaper rash products

Ointment

A suspension or emulsion semisolid dosage form that contains < 20% water and volatiles and > 50% of hydrocarbons, waxes, or polyethylene glycols as the vehicle for external application to the skin.

Cream

An emulsion semisolid dosage form that contains > 20% water and volatiles and/or < 50% of hydrocarbons, waxes, or polyethylene glycols as the vehicle for external application to the skin.

Gel

A semisolid dosage form that contains a gelling agent to provide stiffness to a solution or colloidal dispersion for external application to the skin. May contain suspended particles.

Lotion

An emulsion liquid dosage form for external application to the skin.

Paste

A semisolid dosage form that contains a large proportion (20-50%) of solids finely dispersed in a fatty vehicle for external application to the skin.

What CYP enzyme is skin-specific?

CYP2B12

What racial variations affect percutaneous drug permeation?

- Ceramide content

- Stratum corneum structure

- Filaggrin

What physicochemical approaches can be taken to enhance skin permeation?

- Log P

- Molecular weight

What formulation approaches can be taken to enhance skin permeation?

- Drug concentration

- Surface area

- Spreading/wetting

- Multiple dosing

What stratum corneum modulation approaches can be taken to enhance skin permeation?

- Hydration

- Occlusion

- Temperature

- Chemical enhancer

What active/feedback devices can be used to enhance skin permeation?

- Iontophoresis

- Phonophoresis

- Ultrasonic

- Microneedles

Iontophoresis

Using electric current to drive drug ions through the skin

Phonophoresis

Using ultrasonic waves to enhance drug permeation

How does hydration increase drug permeability?

Stratum corneum swelling

What is the optimal log P range for drugs for skin permeation?

1-5

What is the ideal molecular weight for drugs for skin permeation?

Less than 500 daltons

What kind of drugs does the stratum corneum require for good drug permeation?

Balanced HLB drugs

How does temperature increase percutaneous absorption?

Increases diffusion and blood flow

Which law defines passive drug diffusion through the skin?

Fick's law

How does occlusion increase percutaneous absorption?

Prevents water evaporation, increasing hydration

kp

Permeability coefficient

The speed of transport across the skin in cm/h

What are the 3 chemical enhancers used to increase skin permeation?

- DMSO

- Ethanol

- Tween

What should an ideal semisolid base do?

- Not produce irritation or sensitization

- Not slow wound healing

- Be smooth and odorless

- Be physically and chemically stable

- Be compatible with other dermatological medications

What is the composition of oleaginous ointment bases?

Oleaginous compounds

What is the composition of absorption ointment bases?

- Oleaginous base

- W/O surfactant

What is the composition of W/O emulsion ointment bases?

- Oleaginous base

- Water (< 45% w/w)

- W/O surfactant (HLB ≤ 9)

What is the composition of O/W emulsion ointment bases?

- Oleaginous base

- Water (> 45% w/w)

- O/W surfactant (HLB ≥ 11)

What is the composition of water-miscible ointment bases?

Polyethylene glycols

What is the water solubility of oleaginous ointment bases?

Insoluble

What is the water solubility of absorption ointment bases?

Insoluble

What is the water solubility of W/O emulsion ointment bases?

Insoluble but contain water

What is the water solubility of O/W emulsion ointment bases?

Insoluble but contain water

What is the water solubility of water-miscible ointment bases?

Soluble

What is the spreadability of oleaginous ointment bases?

Difficult

What is the spreadability of absorption ointment bases?

Difficult

What is the spreadability of W/O emulsion ointment bases?

Moderate to easy

What is the spreadability of O/W emulsion ointment bases?

Easy

What is the spreadability of water-miscible ointment bases?

Moderate to easy (depending on concentration)

What is the washability of oleaginous ointment bases?

Nonwashable

What is the washability of absorption ointment bases?

Nonwashable

What is the washability of W/O emulsion ointment bases?

Non- or poorly washable

What is the washability of O/W emulsion ointment bases?

Washable

What is the washability of water-miscible ointment bases?

Washable

What is the stability of oleaginous ointment bases?

Hydrocarbons better

What is the stability of absorption ointment bases?

Hydrocarbons better

What is the stability of W/O emulsion ointment bases?

Unstable, especially alkali soaps and natural colloids; nonionics better

What is the stability of O/W emulsion ointment bases?

Unstable, especially alkali soaps and natural colloids; nonionics better

What is the stability of water-miscible ointment bases?

Stable

Will oleaginous ointment bases absorb an aqueous solution of a drug?

No

Will absorption ointment bases absorb an aqueous solution of a drug?

To some extent

Will W/O emulsion ointment bases absorb an aqueous solution of a drug?

Not a significant amount

Will O/W emulsion ointment bases absorb an aqueous solution of a drug?

Not a significant amount

Will water-miscible ointment bases absorb an aqueous solution of a drug?

Will absorb water to some extent

Are oleaginous ointment bases occlusive?

Yes

Are absorption ointment bases occlusive?

Yes

Are W/O emulsion ointment bases occlusive?

Sometimes

Are O/W emulsion ointment bases occlusive?

No

Are water-miscible ointment bases occlusive?

No

What is the effect of oleaginous ointment bases on skin permeation?

Fair