Formulation of Advanced or Complex Medicines 20

Question 1

How does disintegration work?

Answer 1

First stage in releasing the active ingredient from a solid oral dosage form

Types of disintegration
- tablets
- dissolution or rupture of coating, break-up of core into primary granules
- capsules
- rupture of shell, release of contents
- soft gelatine - dispersion of liquids
- hard gelatine - dispersion of dry solid formulations, liquids or semi solid materials

Question 2

How is disintegration measured?

Answer 2

Oscillating tube with wire mesh base
- nominal aperture 2.00 mm
- initial limit is all parts of dosage form must have gone through mesh by specified time

Question 3

What are the problems with disintegration testing?

Answer 3

Imprecise end point
Parts of capsule shell adhere to mesh blocking openings

Question 4

Why is disintegration testing limited?

Answer 4

No IV/IV correlation
- in vitro/in vivo
Good disintegration does not assure product works
- primary particles can remain unchanged
Conversely, if it does not disintegrate there is a problem

Question 5

How are enteric coated products tested for disintegration?

Answer 5

Standard disintegration apparatus
- operate for 2 hours in 0.1M HCl
- not water!

Tablets should show no signs of cracks in coating
Capsule shells should show no signs of rupture or disintegration

Change medium to a phosphate buffer at pH 6.8 for one hour
- same as small intestine

All dosage forms should have disintegrated

Question 6

What solid oral dosage forms can be placed into a rotating basket for dissolution testing?

Answer 6

Solid forms
Floaters
Beads
Modified release
Suppositories

Question 7

What solid oral dosage forms can be placed into a paddle basket for dissolution testing?

Answer 7

Solid forms
Modified release
Transdermal patches

Question 8

How can floating capsules be tested for dissolution?

Answer 8

Place them in an inert wire helix

Question 9

What is validation?

Answer 9

Action of proving, in accordance with the principles of Good Manufacturing Practice (GMP) that any procedure, process, equipment, material, activity or system actually leads to the expected results

Question 10

What is qualification?

Answer 10

Act of providing that any equipment works correctly and actually leads to the expected results
The word ‘validation’ is sometimes widened to incorporate the concept of qualification