Modern production of Pharmaceuticals

Dr.Norbert Pollinger
This presentation handled three case studies for a real time problems faced by Glatt
customers and was solved by Glatt services :
Rule no 1 the simpler, the more efficient and the less work to do.
1st case study was about:
A lab scale batch of solubility of API HCl at 25 C
Tablets with HS Granules followed by pilot scale with pre-milled API including the following
process:
1. Premilling of API
2. High shear granulation.
3. Drying
4. Tabletting
So
The pre-milled 1st API has good quality.
While the air jet milled 2nd API had a Compactability and Hardness.
When we analyzed the process we found that:
1. The crystallinity and the array diffraction were the same.
2. Upon SEM pictures we found that the powder generated from the air jetted mill was finer.
3. Particle size distribution showed no big difference .
How to solve problem:Design space for process
They used interrelationship diagraph and determined that the quantity of water was the key
factor for the finer powder.
Modified quantity of water, modify the ration of solute to water we found that the less the
water the harder the tablet.
From the process analytical technology the continuous monitoring of the Torque
measurements.
2nd Case study was about:
A coated tablet taste masked granules where its process took about 7 hours in preparation:
1. Milling
2. FBD bottom spray
3. Discharge
4. Sieve (Calibrate)
5. FBD Coating bottom spray
6. Sieve (Calibrate)
However using the Eyecon Technology involving determining particle size distribution allowing
us the continous verification of the particle size currently in the fluid bed Dryer the new
process took about 30 minutes:
1. Milling of API
2. FBD coating bottom spray
3rd Case study was about:
How to increase bulk density of granules.
Tangential spray produces about 30% denser granules than top spray
Moisture content in the powder affects the bulk density of the powder and hence Glatt
provided an online moisture measurement instrument.

Aspects on compression of bilayer tablets:

Eng. Andreas Bornhovd
Challenges during compression of the bilayer tablets:
1. Keep horizontal bisection line at acceptable height.
2. Precise dosing
3. Delamination of layers
4. Losses of Yields
5. Cross contamination with the other powder.
Hardware requirements:
Special equipped machine
Each layer has its own filling station Fill-omatic Tabletting speed is limited
Lower dose size (volume) should be on the upper limit with ration about 70/30
The maximum weight of the 2nd layer is based on the maxiumum penetration depth of
the upper punches in the die i.e. The dose height of the 1 st layer.
Penetration depth of 1st layer determines the fill depth of the 2nd layer.
If 1st bilayer is compressed too hard, there will be no adhesion between the 1 st layer and the
2nd layer.
0.2 0.8 kN is the perfect range for compression of the 1 st layer to allow aeration with
maximum adhesion between layers.
Note that the upper punch never decrease after the compression of the 1 st layer.
Maximum volume of 2nd layer is 8 mm
Volume of the 2nd layer depends on the depth of the 1st layer.
Ideal pre-compression limit of the 2nd layer is 0.5 3.0 kN
Basic dynamic operation sequence
Pneumatic ejector, pneumatic adjustment of lower main compression roll
The most common problems
1- Centrifugal forces bevealed bisector
Precompression force too low
Decrease cylindrical height of the compression side 1
Decrease machine speed
If capping occurs its recommended to compress tablets in the upper part of the die