Tablets and tableting
Tablets: formulation and compaction
Tablets are the most used form of administration in pharmacy (+70% of all drugs used)
- Easy and comfortable use for the patient
- High dosing precision
Large scale industrial production
- Constant and reproducible quality
- A lot of experience in the industry
- Stable, because it is dry
- Reduced transport costs
High-quality production of tablets: no corners/sharp edges, so the round or oblong are
preferred.
How are tablets produced?
Tablets are a compaction of powder blends made by wet granulation, dry granulation and
direct compaction after blending of powers.
Wet granulation
1. Weighing
2. Blending of powders in a mixer homogenous mixture
3. addition of binder fluids (containing binder)
- Binder: polymers that transfers into a sticky mass in presence of water and
provide binding.
4. Granulation (agglomeration) (mixer, fluid bed)
5. Drying the liquid out in an oven or fluid bed)
6. screening (0.5-1.5 mm)(D(50) 70-200 micrometer)
7. blending with glidants and lubricants
- Glidants: promote granule flow and tableting power mixture more
uniform filling of the template, and thus a higher uniformity of mass. (talc,
silicium dioxide)
- Lubricants: minimizes friction between particles and between particles/tablet and
template during tableting. Non-binding or non-smearing materials that prevent sticking
to the punches and dies. Often lipophilic and with poor binding and dissolution
properties.
Magnesium stearate (Optimal lubrication but very bad for binding and dissolution) /
Sodium stearylfumaraat (PRUV) / Glyceryl behenate (Compritol) / Glyceryl
monostearate (Myvaplex) / Hydrogenated castor oil (ricinusoil) / Stearic acid /
Polyethyleenglycol 6000 (PEG 6000, hydrophilic !)
8. Compaction of tablets
- Improve flowability of the powder mass.
- Prevent segregation and improve content uniformity
- Usually contain a diluent, a binder, a disintegrating agent, a glidant, and a lubricant.
, Agglomeration (Desired size: growth and wear and break in equilibrium)
1. Nucleation: two or more primary particles are bound together by a little droplet of
liquid.
2. The formed nuclei grow by
- Layering: new primary particles added to the formed nuclei.
- Coalescence: the joining or merging of elements to form one mass or whole
3. Wear and break: primary particles or agglomerates are removed from the larger granule.
Fluid bed granulation
The primary particles are present in a huge cone through which air is blown. Particles
start moving through the air. Liquid is sprayed on the particles. Because of the
continuous movement, the granules are being formed. There is little shear excerted
upon this granule: particles are in fluidised state. Once droplet has hit the particles,
the water starts to evaporate. A lot of primary nuclei are being formed an there is
little wear and break. Porous agglomerates/granule material. Less dense granule
material.
High shear mixer
Propellers and impellers are present in the high shear mixer in a bowl, in which the
powder mix and droplet of liquid is added. These two moves rapidly (200
rotations/minute). Continuously compacting powder causes a dense granule material.
High risk of adding too much liquid. Dynamic equilibrium between growth and wear.
Dry granulation
1. Weighing
2. Blending of powders homogenous mixture
3. Compaction (roll compactor)
4. Crushing of compacts
5. Blending with glidants and lubricants
6. Compaction of tablets
- Difficult to control the forces exerted on the powder mixture by the roll compactor.
(too high no tablet formed)
- Many dust
- Particles bind together via interparticle forces (vd Waals forces)
Direct compression
1. Weighing the materials
2. Blending
- Blend the drug and excipients.
- Blend lubricants and glidants.
3. Compaction of tablets
Tablets: formulation and compaction
Tablets are the most used form of administration in pharmacy (+70% of all drugs used)
- Easy and comfortable use for the patient
- High dosing precision
Large scale industrial production
- Constant and reproducible quality
- A lot of experience in the industry
- Stable, because it is dry
- Reduced transport costs
High-quality production of tablets: no corners/sharp edges, so the round or oblong are
preferred.
How are tablets produced?
Tablets are a compaction of powder blends made by wet granulation, dry granulation and
direct compaction after blending of powers.
Wet granulation
1. Weighing
2. Blending of powders in a mixer homogenous mixture
3. addition of binder fluids (containing binder)
- Binder: polymers that transfers into a sticky mass in presence of water and
provide binding.
4. Granulation (agglomeration) (mixer, fluid bed)
5. Drying the liquid out in an oven or fluid bed)
6. screening (0.5-1.5 mm)(D(50) 70-200 micrometer)
7. blending with glidants and lubricants
- Glidants: promote granule flow and tableting power mixture more
uniform filling of the template, and thus a higher uniformity of mass. (talc,
silicium dioxide)
- Lubricants: minimizes friction between particles and between particles/tablet and
template during tableting. Non-binding or non-smearing materials that prevent sticking
to the punches and dies. Often lipophilic and with poor binding and dissolution
properties.
Magnesium stearate (Optimal lubrication but very bad for binding and dissolution) /
Sodium stearylfumaraat (PRUV) / Glyceryl behenate (Compritol) / Glyceryl
monostearate (Myvaplex) / Hydrogenated castor oil (ricinusoil) / Stearic acid /
Polyethyleenglycol 6000 (PEG 6000, hydrophilic !)
8. Compaction of tablets
- Improve flowability of the powder mass.
- Prevent segregation and improve content uniformity
- Usually contain a diluent, a binder, a disintegrating agent, a glidant, and a lubricant.
, Agglomeration (Desired size: growth and wear and break in equilibrium)
1. Nucleation: two or more primary particles are bound together by a little droplet of
liquid.
2. The formed nuclei grow by
- Layering: new primary particles added to the formed nuclei.
- Coalescence: the joining or merging of elements to form one mass or whole
3. Wear and break: primary particles or agglomerates are removed from the larger granule.
Fluid bed granulation
The primary particles are present in a huge cone through which air is blown. Particles
start moving through the air. Liquid is sprayed on the particles. Because of the
continuous movement, the granules are being formed. There is little shear excerted
upon this granule: particles are in fluidised state. Once droplet has hit the particles,
the water starts to evaporate. A lot of primary nuclei are being formed an there is
little wear and break. Porous agglomerates/granule material. Less dense granule
material.
High shear mixer
Propellers and impellers are present in the high shear mixer in a bowl, in which the
powder mix and droplet of liquid is added. These two moves rapidly (200
rotations/minute). Continuously compacting powder causes a dense granule material.
High risk of adding too much liquid. Dynamic equilibrium between growth and wear.
Dry granulation
1. Weighing
2. Blending of powders homogenous mixture
3. Compaction (roll compactor)
4. Crushing of compacts
5. Blending with glidants and lubricants
6. Compaction of tablets
- Difficult to control the forces exerted on the powder mixture by the roll compactor.
(too high no tablet formed)
- Many dust
- Particles bind together via interparticle forces (vd Waals forces)
Direct compression
1. Weighing the materials
2. Blending
- Blend the drug and excipients.
- Blend lubricants and glidants.
3. Compaction of tablets
