Formulation of Advanced or Complex Medicines 28

Question 1

How do ion exchange tablets work?

Answer 1

Basic ionic exchange resin and acidic drug

Stomach
- resin salt + HCl = resin chloride and acidic drug
Intestine
- resin salt + NaCl = resin chloride + sodium salt of drug

Acidic ionic exchange resin and basic drug

Stomach
- drug resinate + HCl = acidic resin + basic drug
Intestine
- drug resinate + NaCl = sodium resinate + basic drug

Question 2

What is drug release stimulated by in an ion exchange system?

Answer 2

Charged ions in the GI tract
- relies on ions
- not pH or enzymes

Question 3

What affects the ionic environment of the stomach or intestine?

Answer 3

What affects the ionic environment of the stomach or intestine?

Question 4

What is the function of the skin?

Answer 4

Skin protects us, warns us, maintains us and defines us

Question 5

Why is the skin a good drug delivery target?

Answer 5

Skin is plentiful, readily accessible and can be monitored easily

Question 6

What are the advantages of transdermal drug delivery?

Answer 6

Reduced dosage frequency
Improved patient acceptance, convenience and compliance
- no needles
- self administration
Sustained therapeutic action
Reduced first-pass effect and GI incompatibility
Diminished side effects
- opioids via patch have fewer side effects than oral
More consistent delivery of drug
- constant drug levels
Retrievable dosage form that facilitates terminates of dosing

Question 7

What are the limitations of transdermal drug delivery?

Answer 7

Only suitable for certain molecules
- potent
- permeable
Skin irritation
Lag time
Cost

Question 8

How does direct transcellular path through stratum corneum work?

Answer 8

Solutes permeate directly across the stratum corneum, repeatedly partitioning between the lipophilic intercellular space and the hydrophilic corneocyte, passing across the cornified cell envelope

Question 9

How does tortuous intercellular path through stratum corneum work?

Answer 9

Drug stays in lipid domains

Question 10

How do the corneocytes change as you move through the skin?

Answer 10

Corneocytes flattened and dehydrated towards outer surface

Question 11

What are the two most important determinants of rate and extent of permeation across skin?

Answer 11

Skin/vehicle partitioning
Diffusivity through the stratum corneum

Question 12

What are the most important attributes of a skin-permeable molecule?

Answer 12

Daily dose
- <10 - 20 mg/day
Half life
- 10 hours or less
Molecular weight
- < 500 Da
Melting point
- < 200C
- more soluble
Partition co-efficient (LogP)
- 1 - 4
Non-irritating
Non-sensitizing

Question 13

Which competing processes can significantly modify the degree to which material within the stratum corneum is ultimately absorbed?

Answer 13

Penetration vs metabolism
Penetration vs
- exudation
- abrasion
- desorption
- desquamation
- washing

Question 14

How can penetration of drug across the stratum corneum be improved?

Answer 14

Modify drug
- improve properties
Modify formulation
- increase driving force
Alter partition
Aid diffusion
Change properties
- metabolise prodrug

Question 15

Why is hair follicle permeation useful?

Answer 15

Surface area of follicle wall much greater than area of follicle orifice, increasing area available for permeation into epidermis and dermis

Dense capillary networks around base of both hair follicles and sweat ducts provide good systemic access for most molecules that can permeate to those regions

Question 16

How do penetration enhancers work?

Answer 16

Cause reversible damage to stratum corneum
- disrupt highly ordered packing of lipids
Interacting with intercellular proteins
Optimising thermodynamic activity of drug in vehicle and/or skin
- altering affinity for the base or drug concentration
Increasing drug diffusivity in the stratum corneum
Establishing a drug reservoir in the stratum corneum
Increasing solubility of the active