Tablet Manufacture and Testing (M2.B) Flashcards
Mark Lecture 2.A of 4
What are the 3 methods of Tablet manufacture, using granulation?
- Wet Granulation
- Dry Granulation or granulation by preliminary compression
- Direct Compression
What are a few advantages of using granules for compression over powders?
- Granules have better flow and discharge from hoppers
- Granules pack down easily to form strong tablets
- granules do not clog equipment
- Granules of uniform size reduces the risk of particle segregation
What are a few disadvantages of using powders to compress into tablets over granules?
- Poor discharge from hoppers (rat-holing and bridging)
- Segregation caused by machine vibration and varying particle size
- Low packing density so weaker tablets are formed
- Fine powders clog up machinery and stick to die/punch
What are the simple steps involved in compaction of granules to form a tablet
1) The die is filled with granules
2) The top punch repacks (removes air) the powder with an initial compaction
3) The top punch applies a maximal compaction force
4) the top punch and die decompact to release the tablet
What are some potential problems that may arise during compaction? (3)
1) Picking the tablets are left with a pitted appearance
2) The powder sticks to the punch or the die
3) Powder is blown out from the die
Explain the process of Wet Granulation
Explain the Process of Dry Granulation
Why might we chose to use dry granulation over wet granulation?
Some particles do not mix well with water or heat so dry granulation would be the preferred method
In dry granulation what happens after the primary ingredients (API, diluent, lubricant and 0.5 disintegrant) are added to a mixer?
1) The powder is heavily compressed into slugs (large rough tablet) or roller compacted into a ribbon
2) The slugs/ribbon are then reduced into granules and sieved to collect uniform sized granules
3) The uniform granules are then compressed again into the final tablets
Name is an advantage and disadvantage of dry Granulation
+ This method uses no heat or moisture, so preferred when dealing with an API that is sensitive to heat or water
- More lubricant is needed, which may have adverse effects such as weaker tablets or dissolution
Explain the process of Direct compression
What is a direct compression base?
What is the advantage and disadvantage of using one?
A special formulation that provides all the powder properties required for direct compression, such as desirable fluidity, compression and no segregation.
+ It reduces all the steps of processing into simply mixing and compression and can cut costs of manufacture
- An effective direct compression base can cost as much as the drug to formulate
What properties must an effective direct compression base have? (3)
- Have good flow properties
- Have a high bulk density
- Even particle size to reduce segregation
- Have a good compression profile as this means stronger tablets
- Be inert
- Be cheap
What are the advantages of employing direct compression over dry and wet granulation
+ Simpler process (less steps and ingredients)
+ Greater reproducibility (less steps means less opportunity for inconsistencies in results)
+ No liquid or heat involved (caters for heat and moisture sensitive APIs)
What are the disadvantages of employing direct compression over wet and dry granulation?
- More expensive (due to direct compression base development)
- Extensive process validation is required in the mixing phase
- Time spent developing the direct compression base, which may not be effective to another API
- This process is limited to potent drugs
Describe the test for friability
- Take a tablet remove the loose dust and weigh it
- Place tablet in a rotating drum for 100 revolutions at 25 rpm
- Remove loose dust and reweigh
- Mass lost should be less than 1% to pass
Describe the disintegration test for tablets
- tablets are put into a chamber of the disintegration instrument
- Each chamber has a mesh bottom to allow water to move in and out
- The chambers are raised and lowered at a set frequency into 37 degree water
- this essentially mimics dunking
- The tablets break up and leave through the mesh
Pass if, standard tablets are fully dissolved within 15 minutes, coated tablets 60 mins and soluble tablets 3 mins at 15 degrees water
Describe the dissolution test for tablets
- A chamber containing a specified solution kept at 37 degrees and a rotating paddle or rotating basket designed to aggravate the solution
- The tablet is added to the solution which is stirred
- At set intervals samples are removed from the solution, with equal volumes of solution put back in
- The API conc is calculated from each sample producing a curve showing API content release of % dissolution
What does this diagram tell us?
- The greater the level of breakdown of a tablet, the higher the effective surface area and greater level of drug dissolution and absorption
- Tablet rate of dissolution is slow, granules is moderate while fully deaggregated particles are rapid
What is capping?
The splitting of the top or bottom from the tablet
What is lamination?
The splitting of a tablet into 2 or more layer (tends to be horizontal)
