Formulation of Advanced or Complex Medicines 13 Flashcards
What are the stages of compression?
Rearrangement
Plastic deformation
- visco-elastic flow
Brittle fracture
What are the advantages of using hoppers for filling tablets?
First in, first out of powder
No demixing at exit
Requires a constant rate flow
- related to angle of wall and friction
Mass flow hoppers require more head space in building
Funnel flow can lead to segregation of powders by particle size and/or flow properties
What is the advantage of using a paddle feeder?
1,000,000 tablets per hour
High speed machines require faster delivery of granules to dies
Granule flow assisted by rotating paddles that fluidise the granules, reducing attraction between particles
Dies are slightly overfilled then the excess removed to increase consistency of powder dosing
What are the advantages of direct compression?
No heat or moisture
- better product stability
Fewer unit operations
- less handling and segregation
Disintegrates into primary active particles
Less dependent on operator’ skills
What are the disadvantages of direct compression?
Compaction properties of active critical
Excipient properties more critical
- may be pre-granulated and therefore more expensive
No hydrophilisation of surfaces
Small particle size affects flow
- reduced
Difficulty with content uniformity
Potential for post-blending segregation
Sensitivity to over lubrication
- magnesium stearate
May require adaptation to feeding system on tableting machine
How many tablets can be made in a rotary tablet press?
20,000 per hour
- limited by powder flow
What are the advantages of tabletting using dry granulation?
Granulation with no heat or solvents
Increases bulk density
Improves flow
Limits segregation
What are the disadvantages of tabletting using dry granulation?
Loss of compactability
Need high lubricant level
- magnesium stearate
- very hydrophobic
- doesn’t wet well
- might change dissolution
No hydrophilisation of surfaces
Significant recycling of materials
- won’t hold together nicely
What are the advantages of tabletting using wet granulation?
Improves flow properties
Limits segregation tendency
Improves compactibility
Makes surfaces more hydrophilic
Permits addition of a liquid phase
Improves uniformity of bulk density
Facilitates control of particle size
Reduces amount of fine dust
What are the disadvantages of tabletting using wet granulation?
Exposure of active to heat and solvents
Non-uniform distribution of ingredients
Additional excipients required
- binders
- solvents
Many unit operations involved
What final step might tablets need before they are packaged and used?
Tablet coating
Why do some tablets need to be coated?
Protect active pharmaceutical ingredient (API) from light and moisture
Mask flavour of bitter API
- sugar coated ibuprofen
Mask colour variation in raw materials
Improve patient compliance
- good appearance
Aid product identification
- can print on coating
Aid high-speed packaging
- most robust
Coatings can add functional characteristics
- gradual release
- modified release
What properties of the core of the tablet are needed?
Robust enough to survive extra handling involved in coating process
Strong cores made, especially for film coating, using excipients producing tough compact
- microcrystalline cellulose adds plastic component to formulation
What types coating are used on tablets?
Film coating
- most used
Sugar coating
- traditional method
- widely used in confectionary industry
e.g. smarties
Press coating
- minor method
- increasing interest as used to manufacture complex release forms
- uses a special tableting machine to make a tablet, transfer to another die containing coating granules
- more applied to cover tablet and whole lot compressed
What is a film coating on a tablet?
Application of a thin polymer film to tablet surface
- film must be strong enough to withstand mechanical handling
Film coating solution consists of
- film forming polymer
- plasticiser
- colourants
- solvents
- will evaporate
