Solid Oral Dosage Forms - Granules Flashcards
What is Granulation?
Process in which primary powder particles are made to adhere to form larger, multiparticle entities called granules
Classification of granules
- Bulk granules: solve the variation in particle size in bulk powders e.g. methylcellulose granules - used as laxative
- Divided granules: Granulated products sufficient for 1 dose e.g. effervescent granules
- Powdered oral antibiotic syrups: for patients who have difficulty taking capsules and tablets
- Powders for injections: unstable powders in solution; not to be taken orally
Reasons for granulating
- Prevent demixing of the constituents of the powder mix: smaller particles at the bottom, larger particles above; control PSD -> uniform acceptable formulation
- Improve flow properties of the mix: particles with small size, irregular shape/surface are cohesive and retard flow; advantage in making tablets/filling capsules for feeding of high-speed equipment
- Less surface area per unit weight than powders: more stable, less likely to cake in the container than powders
- Improve compaction characteristics of the mix
- Reduction of toxic hazards associated with handling of toxic powder materials
- Less hygroscopic compared to powders -> less cake formation and adherence
- Occupy less volume -> more convenient for storage
- To capture and fuse small quantities of active material
- Prevent powder segregation
Methods for granulation
- Wet
- Dry - Slugging, Roller compaction
What is wet granulation?
Massing of a mix of dry primary powder particles using a granulating fluid (contain volatile and non-toxic solvent and a binder/adhesive)
Advantages of wet granulation
- Improve content uniformity for low dose drugs
- Improve drug dissolution by enhancing wettability through hydrophilization
Disadvantages of wet granulation
- Costly
- Process complexity
- Possible affect on drug substance (if drug is affected by the solvent)
How are granules tested?
- Loss on drying - water content
- Bulk density
- PSD
- Angle of repose, flow gradient
Parameters affecting granulation processes
- Particle size, density and shape
- Moisture sorption, particle wetting
- Impellor torque, compaction rate, velocity of roller - mixing device characteristics
- Binder solution composition, viscosity, droplet size, binder-solid interactions
Dry granulation by:
- Slugging: mix with dry binders then compress into large crude tablets using heavy duty “slugging press” and then mill the slugs to form granules
- Roller compaction: powder blend forced between rollers to form a cake -> cake milled to form granules
Explain particle-bonding mechanism
Bonding mechanism include:
- Adhesion + cohesion force in the immobile liquid films between individual primary powder particles - thin immobile liquid films in a powder effectively decrease the interparticulate distance and increase the contact area between particles
- Interfacial forces in mobile liquid films within granules: pendular state, follicular state, capillary state
- Formation of solid bridges after solvent evaporation: partial melting, hardening binder, crystallization of dissolved substances
- Attractive forces between solid particles - weak electrostatic and vdw forces
- Mechanical interlocking
Mechanism of granule formation
- Nucleation: Particle-particle contact -> adhesion due to liquid bridges -> more particles join -> pendular state -> more agitation -> capillary state -> nuclei for further growth
- Transition: Nuclei grow by addition of single particles to the nuclei/combination of 2 or more nuclei (size suitable for tablets, capsules)
- Ball growth: more agitation -> large spherical granules -> more agitation -> granuule coalescence to produce unusable/overmassed systems
Examples of wet granulators
- Shear granulators
- High speed mixers/granulators
- Fluidized bed
- Spray Drying
- Extrusion
Explain how does shear granulator works
Powder is mixed and fed to a bowl of mixer and granulating liquid is added. Moist mass is then transferred to oscillating granulator and is forced through a sieve screen to form discrete granules. The granules are dried in an oven/fluidized-bed and then blended with lubricant before tabletting
Explain how high speed mixers works
Unmixed powder is placed in a bowl and mixed by rotating impeller then granulating liquid is added with continuous mixing and chopping. Granular product is discharged passing it through a wire mesh to break large aggregates. Granules are then dried in a fluidized-bed, compressed into tablets.
