Granulation 1 Flashcards
What is granulation?
process by which dry primary powder particles are processed to adhere and form larger particles
Why is granulation important?
improves flow properties of the mixture
prevents segregation of the mixture
- differently sized particles cause segregation which affects dose and weight uniformity
improves compaction characteristics of the mixture
- via the use of granulation fluids
reduce the hazard of cake formation for hygroscopic materials
increases bulk density
What are hygroscopic materials?
materials which absorb moisture from their surroundings
What is the difference between wet and dry granulation?
wet
- uses granulation fluid to facilitate agglomeration by formation of wet mass by adhesion
= granulation fluid can be used alone or with a binder
dry
- uses mechanical compression or compaction to facilitate the agglomeration of dry powder particles
What are the properties of a good granulation fluid? What are examples?
must be volatile
- must be able to be evaporated at specific temperatures
= allows removal from the final product
must be non-toxic
- must be safe to use
water - most commonly used
ethanol
isopropanol
What are the advantages and disadvantages of water as a granulation fluid?
advantages
- cheap
- environmentally friendly
disadvantages - has a higher boiling point resulting in longer drying time = affects chemical stability of the drug - can start hydrolysis = affects stability of the drug
What are the different bonding mechanisms of granulation?
adhesion and cohesion forces
interfacial forces
solid bridges
attractive forces
How do adhesion and cohesion forces work?
adhesion and cohesion forces are found in immobile film
- takes place by a sufficient amount of liquid
= moisture content on the drug substance can form immobile films
- immobile film decreases interparticulate distance and increases contact area
= Van der Waals forces increase as it is inversely proportional to the square distance of separation
How do interfacial forces work?
interfacial forces are found in mobile liquid films
- when the added liquid exceeds the amount required to form an immobile layer then the excess forms a mobile layer
dry state
pendular
funicular
capillary suspension
How do solid bridges work?
can occur in three ways
partial melting
- binder with low melting point is used
= pressure causes melting, upon relieving the pressure the binder will crystallise starting the formation of solid bridges
hardening binders
- adhesive binder/polymer (polyvinylpyrolidine/PVP) is used
= binder will form liquid bridges which will harden over time as they are dried/heated
crystallisation of dissolved materials
- binder (lactose) will solubilise/dissolve some of the materials
= solubilised/dissolved material will adhere as the bidder hardens upon drying
How do attractive forces work?
electrostatic forces
- help with powder cohesion during mixing
Van der Waals
- strength increases as particle size decreases
= are stronger than electrostatic forces
What is the mechanisms of granule formation?
nucleation
- formation of a small nuclei as particles come in contact with each other
= adhesion/liquid bridges, pendular state then capillary state which acts as a nuclei
transition
- nuclei grows larger as single particles are added to the nuclei by pendular bridges
= a limited amount of nuclei are bound
ball growth
- further nuclei growth by different mechanisms
= coalescence, breakage, abrasion transfer, layering
What are the different mechanisms of ball growth?
coalescence
- granules join to form a larger granule
breakage
- granules (1) break into other fragments that adhere to other granules (2)
abrasion transfer
- attrition (reduction) of materials from granules during agitation and adhere to other granules
layering
- addition of a second batch of the powder mix that form a layer around the granule
