powders 6 Flashcards
what is granulation
The process in which a mixture of primary powder particles form larger, homogeneous multi-particle entities called granules
why granulate?
-improve powder flow
to prevent segregation
to improve compaction
what is wet granulation
The API and excipients are mixed
Wetting agent (granulating fluid) is introduced and a wet mass is formed
The wet mass is reduced in size (to form granules) by either chopping it with a blade of forcing it through a sieve
The granules are dried
The lubricant is added
Tablets are compressed
what is dry granulation?
The API and excipients are mixed;
The mixture is compressed between rollers to produce a sheet or flakes of material
The dry sheets/ flakes are reduced in size by milling
The granules are sieved to separate the required fraction;
The lubricant is added;
Tablets are compressed
what is melt granulation
Granulation process which uses a thermosetting material (hot-melt binder) to bind the powder particles into granules
Water/liquid –free alternative to wet granulation
The melt-binder can be introduced as dry excipient and mixed while heated or can be melted and sprayed on to the powder in the mixer/granulator
The mechanism of granule formation is similar to the wet granulation
Most commonly used melt-binders:
hydrophilic – PEGs (PEG 2000, PEG 3000 and PEG 6000)
hydrophobic – carnauba wax, hydrogenated caster oil and stearic acid
advantage and disadvantage of wet granulation
Wet granulation
Advantages:
relatively lower cost compared to dry granulation
combined purpose machines available (fluid-bed granulator)
Disadvantages:
multiple machines used (mixer, granulator, dryer)
effects of drying times and temperature on drug stability
water/solvent hydrolysis/stability of the drug
advantage and disadvantage of dry
Dry granulation Advantages can be used for materials sensitive to wetting no drying (heat sensitive materials) only one equipment
Disadvantages:
can reduce the compaction properties of the granules
primary powder flowability problems can be observed
segregation of the mixture can occur.
advantage and disadvantage of melt granulation
Advantages:
- no water or organic solvents are used
Disadvantages
thermal degradation
not many alternatives to PEGs
why is drying important
Drying is the process by which liquid is removed from a wet solid
During drying:
1) heat is transferred to the wet material
2) the solvent is transformed into gas and leaves the material
Drying of powders and granulates:
- increases the stability
- improves flowability
wet granulation - shear granulator
- mixing of API and excipients
- formation of damp mass
- granulation - oscillating granulaotor
- drying
Disadvantages: long duration; different equipment used for each step (material loss);
wet granulation - high speed mixture
Available in wide rage of sizes
Mixing, wetting and granulating is performed in one step (matter of minutes).
As such are used extensively in industry
Disadvantage – endpoint monitoring system required – care must be taken not to form larger granules than needed.
Drying of the granules is performed separately
wet granulation - Fluidized-bed granulators
Fluidization used for mixing and drying - very efficient
Wetting liquid introduced through nozzle(s) – droplet and powders collide and granules are formed
Exhaust filter prevent the loss of material
Advantages: - “all-in-one” equipment - reduced labour cost - automation is possible Disadvantages - initial cost - large number of (apparatus, process and product) parameters which affect the granules - optimisation and automation can be a lengthy process
Dry granulation - roller compaction
The powder is compressed between two rollers
Adjustable roller speed – variable compression time
Oscillating granulator often used to break the sheet/ flakes to granules
Advantages:
- ecological and cost effective (no wetting and drying)
- relatively low investment cost
- easy to scale up
Disadvantages
- not all materials respond well to roller compaction, and may lose they in poor re-compaction properties
Extrusion / spheronisation
Steps: Mixing of API and excipients Wet massing Extrusion Spheronisation Screening
Pellets are suitable for some applications, particularly controlled drug release products ( e.g. capsule filled with coated and uncoated pellets)
Main advantage – incorporate high-level of API in a relatively small particulates
(i.e. doesn’t require a lot of excipients)
Driers:
Conductive drying: vacuum oven
Not very common
Primarily used with heat and oxygen sensitive materials
