Powders for Pharmaceutical Use (2/3) Flashcards
What can be the consequence of a bad powder flow be?
Tablets of different weight and dose
Can introduce air into mix causing cappy/lamination of tablets
Define: Capping
When the cap of a tablet breaks off
Define: Lamination
The break up of the tablet into a number of layers, usually occurs in the middle of the tablet
Define: Adhesion
Attraction which occurs between 2 unlike surfaces (e.g. API particle/hopper wall)
Define: Cohesion
Attraction which occurs between 2 like particles (e.g. API/API particles)
Smaller particles are more cohesive
Which forces tend to be involved in adhesion and cohesion?
Van der Waals forces
Electrostatic forces
How does particle shape have an influence on flow?
Spheres have minimal inter-particle contacts compared with flakes
How does particle density have an effect on flow?
More dense particles tend to be less cohesive (flow by gravity instead)
What are the 2 types of flow when a powder leaves a hopper?
Mass flow
Funnel flow
Define: Mass flow
Free flowing
First particle in is first particle out
Whole powder be moves down
PICTURE
Define: Funnel flow
Cohesion or hopper angle means particles at walls stick - causes “rat-holes” in powder bed
Causes erratic flow = poor filling
PICTURE
Define: Segregation
Process whereby, during handling, the different particle sizes in a powder separate
List 4 ways that powder flow can be improved
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
Define: Plastic materials
Deform by changing shape, ductile
Bonds develop with time
Define: Elastic materials
Recover shape elastically after compression removed
If bonding is weak tablet will break by capping or lamination
Define: Brittle materials
Fragment on compression
Exposes new surfaces, can lead to high friability
What is the process if an API is brittle?
May fragment on compression and so may not bind
Can add “plastic” excipient - will deform on compaction and bind fractured particles
What is the process if an API is elastic?
May deform in die and spring back - may not bind
Can add brittle excipient e.g. lactose
Why is it important to measure sticking?
If the powder is sticky it will adhere to punch and die
This can lead to variable tablet weights
Define: Organoleptic properties
Aspects of food or medicines as experienced by the senses
How can the taste of a medicine be improved?
Use water soluble derivatives
Add flavours
Sucrose widely used, sorbitol for diabetic preparations
List 3 therapeutic considerations when designing an oral dosage form
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
List 3 things that are investigated during formulation development
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
What is defined during process development?
Manufacturing steps
Equipment
Personnel needed to manufacture on a large scale
List 3 things that should be considered in dosage form design
Need to consider:
Chemistry/mechanical properties of API (and excipients)
Biopharmaceutics
Therapeutics and patient use
