Powders for Pharmaceutical Use (2/3)

Question 1

What can be the consequence of a bad powder flow be?

Answer 1

Tablets of different weight and dose

Can introduce air into mix causing cappy/lamination of tablets

Question 2

Define: Capping

Answer 2

When the cap of a tablet breaks off

Question 3

Define: Lamination

Answer 3

The break up of the tablet into a number of layers, usually occurs in the middle of the tablet

Question 4

Define: Adhesion

Answer 4

Attraction which occurs between 2 unlike surfaces (e.g. API particle/hopper wall)

Question 5

Define: Cohesion

Answer 5

Attraction which occurs between 2 like particles (e.g. API/API particles)
Smaller particles are more cohesive

Question 6

Which forces tend to be involved in adhesion and cohesion?

Answer 6

Van der Waals forces

Electrostatic forces

Question 7

How does particle shape have an influence on flow?

Answer 7

Spheres have minimal inter-particle contacts compared with flakes

Question 8

How does particle density have an effect on flow?

Answer 8

More dense particles tend to be less cohesive (flow by gravity instead)

Question 9

What are the 2 types of flow when a powder leaves a hopper?

Answer 9

Mass flow

Funnel flow

Question 10

Define: Mass flow

Answer 10

Free flowing
First particle in is first particle out
Whole powder be moves down
PICTURE

Question 11

Define: Funnel flow

Answer 11

Cohesion or hopper angle means particles at walls stick - causes “rat-holes” in powder bed
Causes erratic flow = poor filling
PICTURE

Question 12

Define: Segregation

Answer 12

Process whereby, during handling, the different particle sizes in a powder separate

Question 13

List 4 ways that powder flow can be improved

Answer 13

Change particle size - use sieves to select a particle size distribution
Reduce inter-particle forces - pour slowly, avoid moisture (causes cohesion)
Add excipients - glidants may help
Change manufacturing equipment - e.g. use a vibrating hopper

Question 14

Define: Plastic materials

Answer 14

Deform by changing shape, ductile

Bonds develop with time

Question 15

Define: Elastic materials

Answer 15

Recover shape elastically after compression removed

If bonding is weak tablet will break by capping or lamination

Question 16

Define: Brittle materials

Answer 16

Fragment on compression

Exposes new surfaces, can lead to high friability

Question 17

What is the process if an API is brittle?

Answer 17

May fragment on compression and so may not bind

Can add “plastic” excipient - will deform on compaction and bind fractured particles

Question 18

What is the process if an API is elastic?

Answer 18

May deform in die and spring back - may not bind

Can add brittle excipient e.g. lactose

Question 19

Why is it important to measure sticking?

Answer 19

If the powder is sticky it will adhere to punch and die

This can lead to variable tablet weights

Question 20

Define: Organoleptic properties

Answer 20

Aspects of food or medicines as experienced by the senses

Question 21

How can the taste of a medicine be improved?

Answer 21

Use water soluble derivatives
Add flavours
Sucrose widely used, sorbitol for diabetic preparations

Question 22

List 3 therapeutic considerations when designing an oral dosage form

Answer 22

Length of therapy - consider reducing frequency if chronic
Speed of onset - quick dissolution or sustained released
Age of patient - children prefer solutions, elderly prefer tablets

Question 23

List 3 things that are investigated during formulation development

Answer 23

Are the properties/formulae suitable for manufacture
Can the properties be changed to suit a manufacturing method? - e.g. granulate to improve flow
Can the dosage form be developed and scaled up

Question 24

What is defined during process development?

Answer 24

Manufacturing steps
Equipment
Personnel needed to manufacture on a large scale

Question 25

List 3 things that should be considered in dosage form design

Answer 25

Need to consider:
Chemistry/mechanical properties of API (and excipients)
Biopharmaceutics
Therapeutics and patient use