Granulation Flashcards
Process in which primary powder particles are made to adhere to form larger, multiparticle entities called granules
Granulation
larger, multiparticle entities formed in granulation
granules
general size range of granules
between 0.2 and 4.0 mm
typical size range of granules for capsule and tablet
between 0.2 and 0.5 mm
Reasons for Granulation:
To prevent ________ of the constituents of the powder mix
segregation
[true/false]
granulation is done to improve the flow properties and compaction characteristics of the mix.
true
________ will often result in a wide weight variation within the final product owing to variable fill of the tablet dies
Poor flow
Poor flow will often result in a wide _______ variation within the final product owing to variable fill of the tablet dies
weight
This is associated with the distribution of the adhesive within the granule and is a function of the method employed to produce the granule
compaction characteristics of the mix
compaction characteristics of the mix is associated with the distribution of the ________ within the granule and is a function of the method employed to produce the granule
adhesive
compaction characteristics of the mix is a function of the ______ employed to produce the granule
method
[true/false]
toxic materials are better handled as powders than granules
false
Granulation of the toxic materials will reduce the hazard associated with the generation of ________ that may arise when handling powders
toxic dust
Materials which are slightly _______ may adhere and form a cake if stored as a powder
hygroscopic
Granules being denser than the parent powder mix, occupy [more/less] volume per unit weight
less
Reasons for Granulation
- prevent segregation of the constituents
- improve the flow properties
- improve the compaction characteristics of the mix
Other reasons:
1. reduce the hazard associated with the generation of toxic dust from handling powders;
2. slightly hygroscopic materials may adhere and form a cake if stored as a powder;
3. being denser than the parent powder mix, occupy less volume per unit weight
Methods of Granulation
- Wet granulation
- Dry granulation
granulation method that involves wet massing
Wet granulation
Involves the massing of a mix of dry primary powder particles using a granulating fluid
Wet Granulation
in wet granulation, fluid contains a solvent which must be _____ so that it can be removed by drying and be ________
volatile; non-toxic
[true/false]
granulating liquid may be used either alone or not
true
in wet granulation, granulating liquid may be used alone or, more usually, as a solvent containing a dissolved ______ which is used to ensure particle adhesion once the granule is dry
adhesive
Wet mass is forced through a _______ to produce granules which are then dried
sieve
in dry granulation, Primary powder particles are aggregated under [high/low] pressure.
high
dry granulation process where a large tablet is produced in a heavy duty tabletting press
slugging
large tablet is also known as ______
slug
[true/false]
roller milling is when powder is squeezed between two rollers to produce a sheet material
false
roller compaction
instrument used dry granulation where powder is squeezed between two rollers to produce a sheet material
roller compaction
after aggregation in dry granulation, intermediate products are broken using a suitable _______ technique to produce granular material
milling
after milling in dru granulation, granular material is usually _______ to separate the desired size fraction
sieved
[true/false]
unused fine material from dry granulation may be reworked to avoid waste
true
May be used for drugs that do not compress well after wet granulation, or those which are sensitive to moisture
Dry Granulation
(3) Wet granulators
- Shear granulators
- High speed mixer/granulators
- Fluidized bed granulators
(2) Dry granulator
- Sluggers
- Roller compactors
Shear Granulators include (3)
planetary mixer, granulator (oscillating granulator), drying oven
3 major disadvantages of shear granulators are due to ______
tray drying
3 major disadvantages of shear granulators (due to tray drying)
(a) drying time is long;
(b) dissolved material can migrate to the upper surface of the bed of granules, as the solvent is only removed from the upper surface of the bed on the tray; and
(c) granules may aggregate owing to bridge formation at the points of contact of the granules
in shear granulators tray drying:
drying time is (long/short)
long
in shear granulators tray drying:
dissolved material can migrate to the (upper/lower) surface of the bed of granules, as the ________ is only removed from the upper surface of the bed on the tray
upper; solvent
in shear granulators tray drying:
granules may aggregate owing to _______ at the points of contact of the granules
bridge formation
shear granulators:
To deaggregate the granules and remix them, a ________ is necessary after drying
sieving
Alternative method is to dry the granules in shear granulators is to use a _______
fluidized bed drier
wet granulator Used extensively in pharmaceutics
High Speed Mixer/Granulators
mixing, massing and granulation are all performed within a few minutes in the same piece of equipment.
advantage of High Speed Mixer/Granulators
The process needs to be controlled with care as the granulation progresses so rapidly that a usable granule can be transformed very quickly into an unusable, overmassed system
High Speed Mixer/Granulators
High Speed Mixer/Granulator is also sensitive to variations in raw materials, but this may be minimized by using a ________
suitable endpoint monitor
Diosna/Fielder and Collette-Gral Mixer
High Speed Mixer/Granulators
Machine that have a stainless steel mixing bowl containing a 3-bladed main impeller, which revolves in the horizontal plane, and a 3-bladed auxiliary chopper (beaker blade) which revolves either in the vertical or the horizontal plane
Diosna/Fielder
Diosna/Fielder Machine has a stainless steel mixing bowl containing a 3-bladed ______, which revolves in the horizontal plane, and a _______ auxiliary chopper (beaker blade) which revolves either in the vertical or the horizontal plane
main impeller; 3-bladed
Variation of the Diosna/Fielder type of design
Collette-Gral Mixer
Based on the bowl and overhead drive of the planetary mixer, but the single paddle is replaced by two mixing shafts
Collette-Gral Mixer
in Collette-Gral Mixer, one shaft carries ____ blades, which rotate in the horizontal plane at the (top/base) of the bowl, and the second carries (bigger/smaller) blades which act as the chopper and rotate in the horizontal plane in the (upper/lower) regions of the granulating mass
three; top; smaller; upper
operation principle is similar to Diosna/Fielder
Collette-Gral Mixer
Similar design and operation to fluidized bed driers
Fluidized Bed Granulators
powder particles are fluidized in a stream of air, but in addition granulation fluid is sprayed from a nozzle on to the bed powders
Fluidized Bed Granulators
Fluidized bed granulation has (many/few) advantages over conventional wet massing
many
in Fluidized Bed Granulators, All the granulation processed, which require separate equipment in the conventional method, are performed in how many unit/s?
one
why can Fluidized Bed Granulators save labor costs, transfer losses and time
All the granulation processes performed in one unit
process can be automated once the conditions affecting the granulation have been optimized
adavantage of Fluidized Bed Granulators
expensive, and optmization of process (and product) parameters affecting granulation needs extensive development work
disadvantage of Fluidized Bed Granulators
needs extensive development work, not only during initial formulation work but also during scale up from development to production
Fluidized Bed Granulators
Spray driers, spheronizers/pettetizers
Fluidized Bed Granulators
Granules made from a solution or suspension of drug alone, a single excipient or a complete formulation
Spray Driers
only used when other methods are not applicable
Spray Driers
Can convert elastic materials into more ductile ones
Spray Driers
Spray dried lactose
Spray Driers
short drying time and minimal exposure of the product to heat owing to the short residence time in drying chamber
advantages of Spray Driers
(considerable/little) deterioration of heat sensitive materials takes place in spray driers
little
Produce pellets that are used for controlled drug release products following coating with a suitable polymer coat and filling into hard gelatin capsules
Spheronizers/pelletizers
Spheronizers/pelletizers Produce pellets that are used for ________ products following coating with a suitable _____ and filling into hard gelatin capsules
controlled drug release; polymer coat
Multistep process used to make uniformly sized spherical particles
Extrusion/Spheronization
Used primarily to produce MULTIPARTICULATES for controlled drug release applications
Extrusion/Spheronization
among methods of producing drug loaded spheres or pellets, only this process has the ability to incorporate high levels of active ingredients without producing excessively large particles
Extrusion/Spheronization
Main Steps of the Extrusion or Spheronization
1. Drying mixing of ingredients to achieve a ________ dispersion
homogenous powder
Main Steps of the Extrusion or Spheronization
2. ________ to produce a sufficiently plastic wet mass
Wet massing
Main Steps of the Extrusion or Spheronization
3. Extrusion to form _____-shaped particles of uniform_______; the extrudate must have enough _________ to deform, but not so much that the extruded particles adhere to other particles when collected or rolled in the spheronizer.
rod; diameter; plasticity
Three classes of extruder based on their feed mechanism
- screw feed extruder (axial or end plate, dome and radial);
- gravity feed extruder (cylinder roll, gear roll, radial) and
- piston feed extruders
extruder may be axial or end plate, dome and radial
screw feed extruder
extruder may be cylinder roll, gear roll, radial
gravity feed extruder
Main Steps of the Extrusion or Spheronization
4. Spheronization to round off these rods into _______ particles
spherical
in spheronization, arrange the transition chronologically:
- dumbbells
- cylindrical particles with rounded edges
- spheres
- cylindrical particles
- ellipsoids
- cylindrical particles
- cylindrical particles with rounded edges
- dumbbells
- ellipsoids
- spheres
Main Steps of the Extrusion or Spheronization
5. Drying to achieve the desired final __________
moisture content
Main Steps of the Extrusion or Spheronization
6. Screening is a/an (required/optional) done to achieve the desired narrow size distribution
optional
Desirable Properties of Pellets (uncoated pellets)
- Uniform _______ shape
- ______ size
- ______ flow properties
- Reproducible packing (into _____ gelatin capsules)
- ______ strength
- ______ friability
- ______ dust
- _______ surface
- ______ of coating
- Uniform spherical shape
- Uniform size
- Good flow properties
- Reproducible packing (into hard gelatin capsules)
- High strength
- Low friability
- Low dust
- Smooth surface n Ease of coating
Desirable Properties of Pellets (Once Coated)
- Maintain all of the previously mentioned properties
- Have desired ______ characteristics
drug release
Process allows the direct manufacture of spheres from dry powder
Rotor Granulation
Freund granulator
Rotor Granulation
Converts primary powder particles into granules using the application of pressure without the intermediate use of a liquid
Dry Granulator
avoids heat temperature combinations that might cause degradation of the product
Dry Granulator
How many piece/s of equipment is/are necessary for dry granulation
two
pieces of equipment are necessary for dry granulation:
- first a machine for ________ into compacts or flakes
- secondly a ______ for breaking up these intermediate products into granules
compressing the dry powders; mill
Dry powders can be compressed using a conventional tablet machine, or more usually, a large heavy duty rotary press
process is known as slugging
compact made in the process of slugging is termed as
slug
compact made in the process is typically _____ diameter by about ______ thick
25mm; 10-15mm
is suitable for breaking the compacts from slugging
Hammer mill
flakes from roller compactors need gentler treatment to break them into granules, and this can usually be achieved by __________
screening alone
Alternative gentler method, the powder mix being squeezed between two rollers to form a compressed sheet
Roller Compactors
_________ form sheets that are normally is weak and brittle and breaks immediately into flakes
roller compactors
