Granulation Flashcards
Define ‘Trajectory segregation’
Larger particles travel greater horizontal distances than smaller particles
Define ‘Elutriation segregation’
Very small particles sediment on top of larger particles
Define ‘Percolation segregation’
Smaller particles drop to the bottom of the powder bed (e,g; in a hopper where movement of particles occur)
State 3 types of segregation due to particle size
1) Trajectory segregation
2) Elutriation segregation
3) Percoltion segregation
Particle density can influence segregation. TRUE or FALSE, How ?
TRUE. Dense particles tend to move to the bottom
Dense particles have greater mass than less dense particles. TRUE or FALSE
TRUE
Advantages of granulation
- Help improve powder flow (increase in powder flow)
- Help provide uniform mix of powders
- Increase density of powder mix
- Reduce risk of dust generation
- Reduces risk of caking of HYGROSCOPIC powders (tend to absorb moisture from air)
- Can be used as dosage form
- An intermediate for tabletting/capsulation
- Helps compaction of powder mix
- Aids wetting of particles
What is the purpose of Granulating fluid ?
- Used in wet granulation process
- Helps aggregate primary powder (wet massing) particles to form granules
What is the purpose of a ‘Binder’ in wet granulation ?
Helps particles adhere together after drying
State 3 properties of granulating fluid
- Non-toxic
- Compatible
- Removable after drying
Name 3 solvents that can be used as a granulating fluid
- Water, Ethanol, Isopropanol
Aggregation of powder particles is also known as ?
Wet massing
Wet massing is controlled by ?
1) Altering fluid volume added
2) Intensity and duration of mixing
Describe the process of wet granulation
1) MIXING of powders
2) WET MASSING
3) GRANULATION - Wet mass is forced through a sieve producing wet granules
4) DRYING
5) SCREENING
State 4 types of particle-particle interaction during wet granulation
1) Pendular
2) Funicular
3) Capillary
4) Droplet
Describe the formation of liquid bridges between particles in the PENDULAR STATE
- Low liquid levels; discrete liquid bridges at points of contact between particles
- Uniform distribution of liquid throughout powder bed
Describe the formation of liquid bridges between particles in the FUNICULAR STATE
- Higher liquid content, PENDULAR bonds COALESCE (come together to form one mass) and liquid bridges form b/wn non-touching points
- Dependant on degree of liquid (or voidage) saturation, usually 25-80%
Describe the formation of liquid bridges between particles in the CAPILLARY STATE
- Liquid saturation >80%
- Granule becomes paste-like and unsuitable for wet sieving
- Tensile strength of granule increases x3 b/wn pendular and capillary state
Describe the formation of liquid bridges between particles in the DROPLET STATE
- Increased liquid converts capillary state into droplet state (undesirable)
- Particle completely enclosed in water droplet and mass takes on slurry like properties
Liquid bridges form between particles of powder. TRUE or FALSE
TRUE
Nature and extent of liquid bridges is dependant on ?
- Amount of liquid added and method of wet massing
How many stages of liquid bridge forming are there ?
4 stages
Agglomerates are constantly formed and destroyed during liquid bridge formation. TRUE or FALSE
TRUE
Name the 2 types of granulation
1) Wet granulation
2) Dry granulation
In wet granulation, particles adhere because of pressure. TRUE or FALSE
FALSE. Particles adhere due because of liquid
In dry granulation, particles adhere because of pressure. TRUE or FALSE
TRUE
State the 3 phases of agglomeration
1) Nucleation
2) Transition
3) Ball growth
Describe Nucleation
- Particle-particle contact and formation of liquid bridges
- Further agitation makes pendular state dense; Pendular state acts as a nuclei for further granule growth
Describe Transition
- Nuclei grows by addition of single particles via pendular bridges OR Two or more nuclei combine
- Wide size distribution is exhibited
Describe Ball Growth
- Granule continues to grow and produces large, spherical granules
- Agitation is stopped (
Define Coalescence
Process where two or more droplets, bubbles or particles merge during contact to form a single daughter droplet, bubble or particle
Describe Partial melting (for formation of solid bridges)
- Pressures used in dry granulation may cause low melting point materials to melt
- Crystallisation of these material helps bond particles when the pressure is relieved
Describe ‘Hardening binders’ and give 2 examples
Hardening binders are binders used in granulating fluid which harden or crystalline upon drying
e. g:
- Synthetic polymers
- Pre-gelatinised starch
Describe the process of crystallisation of dissolved materials
- Soluble powders will dissolve in granulating liquid
- Crystallisation of dissolved substances may occur when granules are dried (e,g: Lactose)
- Slower drying results in larger crystals
State 4 advantages of Wet granulation
1) Reduced segregation of formulations during processing/storage
2) Useful for formulation of tablets with low active ingredient cocentrations
3) Uses conventional excipients
4) Can be post-processed
State 2 disadvantages of Wet granulation
1) Several processing steps needed
2) Concerns over solvents used in process (e.g: Stability of drug, Toxicology of formulation)
Dry granulation is suitable for formulations where ?
- Product is moisture sensitive
- Drug is heat sensitive
- Poor compression is exhibited after wet granulation
Describe ‘Slugging’ in dry graulation
Process used to compress dry powders into oversized tablet (slug)
State the diameter and thickness of a large oversized tablet (slug)
Diameter 25mm
Thickness 10-15mm
A large heavy duty, tablet press is used for the slugging process. TRUE or FALSE
TRUE
What is used in slugging to improve bonding strength in compaction?
Binders
During slugging, Disintegrants can be used as excipients. TRUE or FALSE
TRUE
What are disintegrants ? give an example
‘Something that swells when it hits water and causes breakdown of tablet’ e.g; Starch
What is the role of a Lubricant ?
Added to slugging process to prevent compacts sticking to the punches and dying. (Stops adherence to other surfaces)
What is Roller compaction
A dry granulation process used to make coarse granules prior to final compression
Describe the process of Roller compaction
- Dry powder mix is squeezed b/wn 2 rollers and form a compressed sheet
- Brittle sheet is immediately broken into flakes OR milled into the correct size
Roller compaction process requires LESS lubricant than slugging process. TRUE or FALSE
TRUE
Binders can be added to roller compaction to improve bonding strength. TRUE or FALSE
TRUE
State and describe 5 types of excipients. Give examples where appropriate
- Diluent (filler) e.g. lactose, starch
– Bulks up powder mix - Disintegrant e.g. starch, sodium starch glycolate
– Breaks up granule / tablet in solution - Lubricant e.g. stearates, PEG, SDS
- Binders (bind constituents together)
- Glidant e.g. talc, colloidal silicone dioxide
– Anti-adherent properties
State 3 advantages of DRY granulation
1) Roller compaction and slugging require conventional excipients
2) Methods not commonly associated with degradation/alteration of
drug molecules during processing
3) No heat or solvents required
State 4 disadvantages of DRY granulation
1) Roller compaction requires specialist equipment
2) Segregation of components may occur post processing
3) Issues regarding powder flow may occur
4) Final tablet is usually softer than that produced by wet granulation
State 3 types of Wet granulators
1) Low shear mixers
2) High-speed granulators
3) Fluidised-bed granulators
Name 6 types of granulating agents
1) Hydroxylpropyl methylcellulose (HPMC) 2-8%
– Various MW and viscosities available
– Soluble in water and ethanol
2) Methylcellulose (MC) 1-5%
– Low viscosity grades commonly used
3) Starch 5-25%
– Requires preparation as a paste
4) Pre-gelatinised starch 5-10%
- Easier to prepare than starch
5) Acacia 1-5%
Requires preparation as a paste
– Can result in prolonged disintegration times at
high concentrations
6) Polyvinylpyreolidone (PVP) 2-8%
– Various MW and viscosities available
– Dry or in solution
– Soluble in water and ethanol
What is Granulation ?
The process of collecting particles together by creating bonds between them. Bonds are formed by compression or by using a binding agent
State 7 desirable properties of a granulating fluid
- Non-toxic
- Compatible
- Removable after drying
(on lecture slides)
(according to Clare)
- Cost effective
- Already approved
- Evaporates quickly at lowest temp possible
- Crystalline and able to form more permanent structure
How does the volume of granulating fluid
affect formation of granules ?
‘Too much granulating fluid a slurry tablet as droplet stage is reached and granulation won’t occur. Brittle shape is formed not granules’.
Name an alternative form of granulation asides wet or dry
Spheronisation
Spheronisation produces spherical, uniform sized pellets (therefore is used when spheres are required as dosage form). TRUE or FALSE
TRUE
Spheronisation is used for which drug formulations
- M/R or C/R formulations
State one disadvantage of Spheronisation
This process is more ‘labour intensive’ than other forms of granulation (therefore is only used when other forms are inappropriate)
In Spheronisation, Wet massing is important to produce good quality spheres. TRUE or FALSE
TRUE (Usually higher fluid volumes are required compared to wet granulation)
State the main processes of Spheronisation
1) Mixing
2) Wet massing
3) EXTRUSION
4) SPHERONISATION
5) Drying
6) Screening
What does the Extrusion and Spheronisation process ensure and is equipment required for these processes ?
- Ensures that the particles are uniform and Yes, requires equipment
Water level is critical for optimising the spheronisation process. TRUE or FALSE
TRUE
State (and draw) the shapes from transition of rod-shaped (cylinder) to spherical
particles
Cylinder > Cylinder with rounded ends > Dumbbell > Ellipsoid > Sphere
