Formulation of Advanced or Complex Medicines 12 SODF Flashcards
Where is the liquid distributed in a wet granule?
Dry mix
- no water
Pendular
- bridges between particles
Funicular
- gaps filled in between bridges
Capillary
- all gaps filled in between bridges
- critical point
Kneaded capillary
- particles pushed together and liquid squeezed out
What holds the granule together?
Individual particles accumulate into balls during granulation process
Liquid bridges
- temporary structures
- removed in drying step
Solid bridges
- hardening of binders
- e.g. polyvinylpyrrolidone (PVP)
- crystallisation of dissolved substances
- e.g. lactose
- partial melting
- low melting point materials
- energy of the system is enough to melt some systems
How can wet solids be dried?
Moisture content of wet solids
- kg of water per kg of moisture-free solid
Total moisture content
- not all water can be removed easily
- hemihydrate drug salts need very harsh conditions to remove water which would damage product
- bound vs unbound water
- not all water is bound water
- gelatine capsules are 4% water
Equilibrium moisture content (EMC)
- moisture content of a solid under steady-state ambient conditions
- depends upon temperature, humidity, nature of solid
- water would move back into product after you have removed it
What machinery is used for granulation?
Wet granulation involves the addition of a granulating solution to the powders that will form the granule
- a mix of active and excipients
Two of the common pieces of equipment used are
- high speed mixers/granulators
- fluidised-bed granulators
What are the stages in high speed mixers/granulators?
Powders are added to the high speed mixer/granulator and mixed whilst dry
Granulating solution is then added and further mixing performed until granules are formed
Granules are removed via the discharge port through a wire mesh to exclude oversized granules
The wet granules are then dried
- may be heated
What are the advantages of convective drying on a fluidised bed?
Efficient heat and mass transfer
Drying from all surfaces
Bed temperature can be controlled
Avoids risk of soluble material migration
- caused by solvent evaporation
What is the disadvantage of convective drying on a fluidised bed?
Fines collected in bag filters
- care needed to avoid segregation and loss
What is spray drying of particles?
Droplet -> evaporation from surface -> solute concentration at surface -> hollow sphere -> dry sphere with blow hole
What is dry granulation?
Primary particles formed into granules without the use of liquids by the use of compaction
- used for labile actives that are sensitive to liquids and heat
What are the two steps to dry granulation?
First mix powders
- second compact on heavy-duty machines to form large tablets (slugs) or use roller compactors to form sheets of material
Mill materials to obtain required particle size
What are the advantages of dry granulation?
Use with water and heat sensitive actives
Simple two-step process
Requires less labour and equipment
What are the disadvantages of dry granulation?
Requires actives with compaction properties
- only used for high dose actives
Requires additional excipients for slugging process
- extra lubricant required due to double compression
What is a tablet?
Solid preparation each containing a single dose of one or more active substances, usually made by compacting uniform volumes of particles
How are tablets taken?
Most intended for oral administration
- swallowed whole or after being chewed
- dissolved or dispersed in water before being taken
- retained in mouth where active substance is released
What are the different types of tablets?
Standard
- designed to break up in the stomach and release the active
Chewable
Buccal/sub lingual
Orally- disintegrating
Effervescent
Modified release
Delayed release
