Routes of Administration: Topical Preparations

Question 1

Describe topical drug delivery.

Answer 1

• Administered on tissue surface.
• Treatment of a local condition.
• Site of administration is site of therapeutic action.
• Minimise systemic absorption to minimise side effects.
• Commonly skin (cutaneous/transcutaneous), but could refer to other tissue.

Question 2

What is an ointment?

Answer 2

Drug dissolved or dispersed in a greasy base

Question 3

Describe the features of ointments.

Answer 3

• Occlusive: promotes skin hydration by minimising trans epidermal water loss
• Can be difficult to spread
• patient acceptability could be low

Question 4

What is a cream?

Answer 4

• Semi-solid emulsion
• Multiphase dispersion of oil in water or water in oil

Question 5

What are the advantages of creams?

Answer 5

• Longer residence time than lotion
• Mixable with skin secretions , easily washable
• Excellent patient acceptability

Question 6

What is a gel?

Answer 6

• Semi-solid or viscous liquid, often clear or transparent
• Polymer network interpenetrated by a liquid
• Mostly aqueous: hydrogels or hydro-alcoholic gels
• Drug dissolved or dispersed in liquid component
• May form occlusive film on skin when dried

Question 7

What is a lotion?

Answer 7

• Typically water-based, thus non-occlusive:
• Solution, suspension or emulsion.
• Primarily used for cleansing or disinfection.
• High spreadability: ideal for covering large area thinly.
• Suitable for administration on hairy skin.
• Short residence time: increasing viscosity prolongs
  residence time.

Question 8

What is a foam?

Answer 8

• Dispersion of gas within a liquid.
• Drug dissolved or dispersed in liquid phase.
• Available as pressurised cans.
• Foam generated during use and stable only momentarily.

Question 9

Describe a spray.

Answer 9

• Aerosol: Dispersion of liquid droplets in gas.
• Fine mist generated using propellant in pressurised can.
• Administration without direct skin contact.
• Rapid and even coverage of large surface area.

Question 10

Describe a patch.

Answer 10

• Similar to transdermal patch but for topical delivery.
• Solid dosage form containing drug on an adhesive film.
• Discrete dosage unit enables accurate dosing.
• Provides occlusion, dose retention, and protection of formulation from environmental
  contamination during use.

Question 11

What are the advantages of topical preparations?

Answer 11

• Avoid gastrointestinal drug degradation and hepatic first-pass metabolism.
• Non-invasive, thus well accepted by patients.
• Better drug targeting, thus minimal systemic side effects.
• Easy dose withdrawal in case of adverse reactions.
• Convenient: portable and self-administrable.

Question 12

What are the disadvantages of topical preparations?

Answer 12

• Low skin permeability: only a small selection of drugs deliverable, and even then
  their uptake is slow.
• Skin irritation.
• Difficult to determine dose accurately (e.g., creams, gels, ointments).

Question 13

Name the cellular layers of the human skin.

Answer 13

• Epidermis
• Dermis
• Hypodermis

Question 14

Describe the stratum conreum of the epidermis.

Answer 14

• Dead cells with a hard protein envelope: the cells contain keratin and are surrounded by lipids
• It is the permeability barrier

Question 15

Describe dermal drug transport mechanisms.

Answer 15

• Partitioning: from one medium to another, solubility-driven
• Diffusion: within the same medium down conc. gradient

Question 16

What is skin permeability?

Answer 16

A function of the partitioning coefficient and the diffusion coefficient.

Kp = KD/h
Kp = permeability co efficient
K = partition coefficient
D = Diffusion coefficient
h = Diffusion path length

Question 17

Why are transcellular and paracellular pathways important?

Answer 17

• For traditional dosage forms
• Transcellular route (hydrophilic drugs)
• Paracellular route (lipophilic drugs)

Question 18

What is the shunt pathway?

Answer 18

• Through hair follicles and sebaceous glands

Question 19

State the factors affecting dermal drug transport.

Answer 19

• Drug properties: lipophilicity, molecular weight
• Anatomical site: barrier thickness, hair follicle density
• Age: thickness, hydration, lipid content and microvascular clearance decline with age, corneocytes enlarge with age
• Disease: broken skin = higher permeability, scaly skin = impaired permeability barrier and dehydrated = reduced permeability
• Thickened skin = reduced permeability due to increased diffusional path length

Question 20

What is tape stripping?

Answer 20

• Stratum corneum progressively removed by adhesive tape.
• Drug assayed relative to protein content of the strip.
• Assumes each tape removes materials from single cellular layer.
• Tape constituents may contaminate sample.

Question 21

Descibe human skin for in vitro skin models.

Answer 21

• Closest to in vivo human skin.
• From cadavers or post-operative sources.
• Requires informed consent and ethical approval.

Question 22

Describe animal skin for in vitro skin models.

Answer 22

• Pig skin closest to human skin anatomically and kinetically.
• Murine skin cheap and easy to source.
• Hairless skin models minimise drug transport through follicular pathway.
• Ethical and legal considerations

Question 23

Descibe artificial membranes for in vitro membranes.

Answer 23

• Alternatives to native biological tissue.
• Bio-engineered skin equivalents with cellular components, e.g. Episkin™
• Non-biological polymeric membranes, e.g. Strat-M®
• Validated through correlation studies using a variety of drugs spanning a range
  of structure, therapeutic classes and physicochemical properties.
• Cheap, safe, ethical and highly reproducible.