formulation science

Question 1

how is paracetamol metabolised

Answer 1

Paracetamol is metabolised by 2E1 to NAPQI

At low dose, NAPQI is conjugated with GSH and excreted in urine

At high doses, there is not enough GSH, so NAPQI will react with nucleophilic macromolecules and cause toxicity

Question 2

Why are prodrugs designed?

Answer 2

To overcome solubility, permeability of drug

eg. prodrugs must dissolve in GI fluids before absorption

Question 3

When are prodrugs converted?

Answer 3

Prodrugs dissolve in gastric fluid.

Since prodrugs are more hydrophilic than the active drug, they can permeate less through the intestine. Hence they need to be converted by the enzymes in the brush border of the intestine, becoming the more lipophilic active drug -> pass through the intestine wall

Question 4

What is occlusive effect?

Answer 4

The ability for a preparation (eg. cream) to keep water within the skin as it blocks evaporation, leading to swelling

This helps to improve permeability of drugs as the spaces between the cells in the stratum corneum increases

Question 5

What are water emulsifying ointments for

Answer 5

Take up water, good for cuts with exudates

Question 6

How do surfactants help ointment or creams?

Answer 6

Lower surface tension, help to incorporate more oil component, better stability of the oil in water (or vice versa)

Question 7

What is the hydrophilic gel called? Advantage?

Lipophilic gel? Advantage?

Answer 7

Hydrogel
- easier to spread, more moisture content, cooling effect

Oleogel
- occlusive effect can increase permeability
- longer contact time

Question 8

Ideal physical chemical properties for oral mucosa delivery

Answer 8

LogP 1-3, higher means more lipophilic

MW < 500 Da

Soluble (> 1mg/mL)

Uncharged

Question 9

What are gastro-retention formulations for

Answer 9

Drugs with narrow absorption windows

Locally active in stomach

Unstable in colon

Low solubility at high pH in the colon (hence want to be retained in the stomach longer)

Question 10

What are some strategies for gastro-retention

Answer 10

Floating
Sinking
Mucoadhesion
Size expansion (swelling)

Question 11

Pros and cons of Capsules vs tablets

Answer 11

Capsules
- less irritating to GI tract
- Faster onset than tablets as tablets are absorbed slower
- More even disintegration
- Lesser unpleasant taste

Tablets
- more durable, longer shelf life
- can be split into 2
- More suitable for vegetarians and muslims (gelatin capsule)
- Can contain higher doses of active ingredient