Keele Granulation

Front 1

What is trajectory segregation?

Back 1

Where larger particles travel greater horizontal distances than smaller particles

Front 2

What is Elutriation Segregation?

Back 2

Where very small particles sediment on top of the larger particles

Front 3

What is Percolation Segregation?

Back 3

Where smaller particles drop to the bottom of the powder bed (as in hopper where movement of particles can take place)

Front 4

What are the nine reasons for granulation?

Back 4

-Improves powder flow

-Provides a uniform mix of powders

-Increases density of powder mix

-Reduces risks of dust generation

-Reduces risk of caking of hygroscopic powders

-Dosage form

-Intermediate for tabletting/capsulation

-Helps compaction of powder mix

-Aid wetting of particles

Front 5

What happens during wet granulation?

Back 5

-Powders mixed

-Liquids added in granulation process

-Aggregation of primary powder particles to form granules

-Wet mass forced through sieve, producing wet granules

-Drying

-Milling

-Screening

Front 6

What two type of liquids are used during wet granulation?

Back 6

-Granulating fluid

-Binder

Front 7

What are the features of granulating fluid, and which solvents are used?

Back 7

-Solvents: water, ethanol, isopropanol

-Compatible

-Non-toxic

-Removable by drying

Front 8

What does the binder do?

Back 8

Helps particles adhere together after drying

Front 9

Particle-Particle Interaction during Wet Granulation

Back 9

Front 10

What is the pendular state?

Back 10

-Low liquid levels, discrete liquid bridges at points of contact between particles

-Assumption that there is a uniform distribution of liquid throughout powder bed

Front 11

What is the Funicular state?

Back 11

–Further liquid content, pendular bonds coalesce and liquid bridges form between non-touching points–Dependant on degree of liquid (or voidage) saturation, usually 25-80%

Front 12

What is the Capillary state?

Back 12

-Liquid saturation > 80%

-Granule becomes paste-like and unsuitable for wet sieving-Tensile strength of granule increases x3between pendular and capillary state

Front 13

What is the Droplet state?

Back 13

-Further increase in liquid converts capillary state into droplet state (undesirable)-Particle completely enclosed in water droplet and mass takes on slurry like properties

Front 14

How many stages of bridge formation are there?

Back 14

Four

Front 15

How does adhesion take place during dry granulation?

Back 15

Due to pressure

Front 16

How does adhesion take place during wet granulation?

Back 16

Particles adhere due to liquid

Front 17

What are the three phases of agglomeration?

Back 17

-Nucleation

-Transition

-Ball Growth

Front 18

What happens during Nucleation?

Back 18

– Particle-particle contact and formation of liquid bridges– Further agitation densifies pendular state which acts as a nuclei for further granule growth

Front 19

What happens during Transition?

Back 19

-Nuclei can grow by single particles being added via pendular bridges or two or more nuclei can combine– Wide size distribution exhibited

Front 20

What happens during Ball Growth?

Back 20

– Further granule growth produces large, spherical granules with size increasing over time.– Agitation stopped (would promote further coalescence making over-massed particles)

Front 21

How are solid bridges formed?

Back 21

-Partial melting

-Hardening binders

-Crystallisation of dissolved materials

Front 22

What happens during Partial Melting?

Back 22

–Pressures used in dry granulation may cause melting of low melting point materials

–Crystallisation of the materials helps bond the particles together when the pressure is relieved

Front 23

What are Hardening Binders?

Back 23

-Binders used in granulating fluid harden or crystallise on drying–Synthetic polymers and pre-gelatinised starch

Front 24

What happens when dissolved materials are crystallised?

Back 24

–Some of the powders in the mix may besoluble and dissolved in the granulating liquid–Crystallisation of the dissolved substancesmay happen when the granules are dried eg. Lactose–Slower drying times result in larger crystals

Front 25

What are the advantages of wet granulation?

Back 25

–Reduced segregation of formulation components during storage/processing–Useful for formulation of tablets with low active ingredient concentrations–Uses conventional excipients–Can be post-processed (tablet coating)

Front 26

What are the disadvantages of wet granulation?

Back 26

-Several processing steps needed-Solvents used in process lead to concerns i.e. stability of drugs, toxicology of formulation

Front 27

What are the features of Dry Granulation?

Back 27

-No liquids

-Suitable when product is moisture and heat sensitive and can't be compressed after wet granulation

-Aggregation of primary powder particles to form granules under high pressure

Front 28

How are compacts broken up into granules during dry granulation?

Back 28

A mill/slugging is used

Front 29

What is Slugging?

Back 29

A process used to compress dry powders into a large oversized tablet (slug) using a large heavy press.

Front 30

What happens during Slugging?

Back 30

-Dry powders compressed into tablet around 25mm in diameter, and 10-15mm thick.

-Large heavy duty press is used

-Binder used to improve bonding strength during compaction

-Disintegrant used as excipient

-Lubricant added to prevent compacts sticking to the punches and die

Front 31

What happens during roller compaction?

Back 31

– Dry powder mix squeezed between two rollers to form compressed sheet– Brittle sheet immediatley broken into flakes or milled into correct size– Flakes turned into granules– Can be compacted with binder to improve bonding strength– Roller compaction required less lubricant than for slugging

Front 32

What are the different types of excipients used in granulation?

Back 32

-Diluents

-Disintegrants

-Binders

-Lubricants

-Glidants

Front 33

What are the advantages of dry granulation?

Back 33

-Both roller compaction and slugging require conventional excipients–Methods not commonly associated with degradation/alteration of drug molecules during processing-No heat or solvents required

Front 34

What are the disadvantages of dry granulation?

Back 34

–Roller compaction requires specialist equipment–Segregation of components may occur post processing–May be issues regarding powder flow–Final tablets usually softer than with wet granulation

Front 35

What are the different types of wet granulators?

Back 35

-Low shear mixers

-High-speed granulators

-Fluidised-bed granulators

Front 36

What is Spheronisation?

Back 36

-A form of granulation

-Makes uniform sized spherical pellets

-Used when spheres required dosage form

-Useful for M/R and C/R forms

-More labour intensive

-Wet massing important to produce good quality spheres

Front 37

Transition from rod-shaped to spherical particles

Back 37