Granules and Granulation Flashcards
Powders
Usually a mixture of fine powders, including active ingredient, colours, flavours and sweetening agents
Granules
- Comprise powder particles that have been aggregated to from large particles sufficiently robust to withstand handling
Examples of pharmacutical powder
- Amoxicillin
- Ciplofloxin
- Laxative sachets
Pharmaceutical granules
- Colchicine to treat gout
- Cholecalciferol (Vit D3) for osteoporosis
- Pyronaridine as antimalarial
Granulation
- Dry primary powders are processed to adhere to larger multi particulate entities
Small granules
- 0.2 to 0.4 mm
- Usually used as intermediates to be
mixed with other excipients prior to
tablet compaction or capsule filling
Large granules
- Often dosage forms in their own right
- 1 to 4 mm
Reasons for granulation of powders
- Loosely packed
- Poor flowability
- Not uniform
- Dusty
Reasons for granulation of granules
- Denser
- Good flowability
- Uniform
- Reduce dust
Reasons for granulation
- Prevention of the segregation of constituents of a powder mix
- Improve flow of properties in powder mix
- Improve compaction of powders and uniformity of mix
- decrease toxic dust
- Decrease caking and increase bulk density less storage space
Prevention of segregation after sieving powder
- Small dense particles
to the bottom and large less dense particles to the top
Prevention of segregation after sieving of granules
Granules prevent
segregation of the
constituents of a
powder mix
Sifting segregation
- Up and down motion to segregate into a container
Trajectory segregation
- Side to side motion in a screw conveyor
Fluidisation segregation
- Up and down motion seperating course particles and fluidised fine layers
Angle of repose segregation
- Stone pile where granules fall to either side
Flowability angle of repose
- Angle of repose
- 25-35 degrees good to excellent
- 36-45 degrees fair to passable
- 45-65 degrees poor to very poor
- > 66 degrees very very poor
Tapped density (Df)
Weight of sample/volume of powder after tapping until fully settled
Bulk density (Do)
Weight of sample/Volume of powder when poured into cylinder
Carr’s index
- Df - Do / Df x 100
- Measures strength and stability
- <10 excellent flow property
- > 38 very very poor
Hausner ratio
- Do/Df
- Measure of interparticulate friction
- 1.00-1.11is excellent flow property
- > 1.60 very very poor
Wet granulation step 1
- Blend powder solid drug with excipients
Wet granulation step 2
- Binder (solvent water and ethanol)
- Adhesion and cohesion forces formed due to liquid bridges formed
- Formation of blackberry structure from vander waals and electrostatic forces mechanicaly interlocking
Sugars and natural binder examples
- Sucrose
- Liquid glucose
- Starch paste
- Cellulose
- Alginic acid
- Gelatin
Synthetic/semi-synthetic polymers
- Methyl cellulose
- Ethyl cellulose
- Hydroxypropyl methylcellulose
- Hydroxypropyl cellulose
- Polyvinal alcohol
Wet granulation step 3
- The moist mass is pressed through a sieve to size granules
- Mass too moist string forms
- If mass too dry the granules will fall appart
- Screw feed extruder - axial and radial
- Gravity feed extruder - Cylinder/Gear
Wet granulation step 4
- Primary granules held together by solid bridges hardening binding agent
- Bridges of crystalised drug or excipient from patiral melting/recrystalisation
Wet granulation step 5
- Dried granules are passed through sieve shaker
Limitations of wet granulation: Cost
- Granulation is an expensive process because of labour, time, equipment, energy and space requirements
Limitations of wet granulation: stability and loss of material
- Moisture-sensitive or thermolabile
drugs, as well as those exhibiting polymorphisms - Loosing materials during stages of process
Limitations of wet granulation: Multiple processing step
- Complexity and make validation and
control difficult
-
High-shear granulation equipment
- Shear and compaction force exerted by the impeller causes Mixing, densification and agglomeration achieved through
Equipment for fluid-bed granulation
- Spraying a binder solution onto a fluidized powder bed
Extrusion-spheronization
- Extrudate strands feed rolls cause breakdown into cylinderical pellets
Spray-drying granulation
- Use liquid feed into atomiser add drying gas into drying chamber
- Dry particles collected
Dry granulation Step 1
- Add dry powder which contains drug and excipients
Dry granulation step 2
- Compression of dry powder using roller compaction
- Powder mix is squeezed between two rollers forming flakes
Dry granulation step 3
- Slugging to prepare large tablets that are 25mm in diameter and 10-15mm thick
- The slug tablets from compression machine is placed on the oscillatting granulator (milling machine)
Dry granulation step 4
- Granules are passed through sieve shaker to form sized granules
Limitations of dry granulation
- High force/pressure involved in compaction
- More likely to generate dust and cause environmental contamination
