Transdermal Drug Delivery Systems (TDDS)

Question 1

What is TDDS

Answer 1

Facilitate the passage of drugs through the skin into the general circulation for systemic effects
Skin is not the target.
Drug should pass to the blood without buildup in the dermal layer

Question 2

Advantages of TDDS

Answer 2

• Variation associated with oral therapy are avoided - GI variations -> better absorption control
• By-passes the first-pass metabolism
• Continuity/ability to terminate medication
• Multiday therapy with single application
• Avoids risk and inconvenience of parental therapy
• Extends activity of drugs with short half lives
• May provide an alternative when oral route is unsuitable (unconscious, uncooperative, cannot swallow food)
• Better patient compliance

Question 3

Disadvantages of TDDS

Answer 3

• Only potent drugs are suitable due to skin impermeability
• Lipophilic (moderately) uncharged drugs with low MW only
• Some patients develop contact dermatitis
• Components, formulation and drug must be non-irritating and non-sensitizing to the skin

Question 4

Pathways of Transdermal permeation

Answer 4

• Small polar particles - intercellular
• Small non-polar particles - intracellular
• Large polar compounds - sweat pores, hair shaft

Question 5

Factors that determine the rate of drug passage through skin

Answer 5

1. Drug factors
   - Hydrophilic or lipophilic (penetrate better) but too lipophilic may cause API not to cross
   - pKa - ionization decreases penetration, neutral best
   - MW 100-800 permeate skin, ideal MW is 400
   - Particle Size - smaller -> penetrate faster
2. Delivery system
   - drug concentration/solubility - increase -> better penetration
   - vehicle viscosity - decreases diffusion coefficient
   - vehicle composition - non-aqueous solvents increase penetration
   - penetration enhancers - disrupt skin surface -> faster penetration
   - area of absorption - increase -> increase absorption
3. Physiological conditions in skin
   - bonding: accumulation decreases initial drug transport
   - sebum: pH, amount and composition alters passage
   - Hydration, skin age, location and condition: occlusive dressings increase hydration -> increase penetration rate
   - thickness: thin skin -> increase penetration rate
   - Injury: open cuts and grazes -> increase penetration rate

Question 6

What are the percutaneous absorption enhancers

Answer 6

• Chemical - increase skin permeability by reversibly damaging/altering the physicochemical nature of the stratum corneum -> decrease diffusional resistance -> increase hydration, change the structure of lipids and lipoproteins
  e.g. acetone, DMSO, DMF, EtOH, Oleic acid
• Physical
  1. Iontophoresis - delivery of ionic drugs into the body using electric current. The driving electrode carriers the same charge as that of the drug and repels the ions, sending them and the drug through; flow of current through the skin decrease its resistance -> increases permeability; electroosmosis, in which solvent flowing through the pores dissolves particles and helps to carry them through the skin.
  e.g. delivery of liocane, amino acids, insulin
  2. Sonophoresis - ultrasonic sound waves increase skin permeability -> increase drug delivery to skin ; sound waves -> cavitation - formation/collapse of gas bubbles, heating - increase pressure and decrease electrical resistance
  => cavitation and heat -> enlargement of intercellular spaces; increased flow of lipids within the membrane
  e.g. salicyclic acid, lidocane, hydrocortisone

Question 7

Types of transdermal system

Answer 7

1. Monolithic systems
   - Active agent is homogeneously dispersed throughout a rate-controlling polymer matrix ( -can be semisolid, liq or gel) and the rate of drug release is controlled by diffusion through the polymer matrix -> rate decreases with time, drug needs time to pass through the matrix
   e. g. nitroglycerine releasing transdermal for angina
2. Reservoir system
   - Drug is enclosed in a reservoir, in liquid/gel form, where the rate of drug release is controlled by its permeation through a membrane; rate remains constant with time if reservoir is maintained at level, no lag time
   e. g. pilocarpine-releasing ocular insert for 4-day continuous for glaucoma treatment, scopalamine-releasing transdermal for motion sickness, nitroglycerine releasing transdermal for angina