1. An efficient replacement of three pieces of
equipment with a single one. A case study in
a pharmaceutical factory
G. Mari

2. Case Study: process change in
the final steps of an API
extraction
• Description of the previous process
• Evaluation of alternatives for improvement
• Description of the new process
• Comparison and advantages description

3. Process steps
• Crystallization
– Difficult (“gummy” phase)
– Several “washings” with alcoholic solution
• Filtration
– Massive solvent removal
• Drying
– Long and “delicate”
– Under vacuum

4. M
N2 ANALYZER O2
Product aqueous solution
loading (~200 lt)
Nitrogen purging is
started

5. M
N2 ANALYZER O2
Continuous
Nitrogen
purging
Alcoholic solution addition
Agitation starts
“Gummy” phase formation
Safetyinterlock

6. M
N2 ANALYZER O2
“Gummy phase settling

7. M
N2
L.A.F.
Supernatant
removal

8. 3 – 4 following “washing” steps
M
N
2
M
N
2
M
N
2

9. M
L.A.F.
Buchner Filter
(static)
Solvent removal

10. L.A.F.
VACUUM
Product manual
loading
and drying

11. Centrifuge
dryer

12. Filter Dryer
Solid product
dicharge valve

13. Filter dryers

14. “GUMMY” PHASE
FILTER
MSOLVENT PRODUCT
Impossibile to
use filter dryer
DISASTER

15. SOLUTION

17. M
FILTER
Product loading
Alcoholic solution loading
Agitation start
“Gummy” phase formation
Modified agitator
Additional
side nozzle

18. M
FILTER
“Gummy” phase
settling

19. M
EXHAUST SOLVENT
Supernatant massive
removal
Continuous
nitrogen purging
The pieces of
equipment is kept
closed

20. M
EXHAUST SOLVENT
Supernatant removal
optimization

21. M M
M
M M
M
M M
M

22. M
EXHAUST SOLVENT
Continuous
nitrogen purging
The pieces of
equipment is kept
closed
Final solvent filtration
The agitator helps the
solvent removal

23. M
VACUUM
Drying

24. M
Product
(powder)
discharge

25. Quality advantages
• No transfer in 3 different pieces of
equipment (GMP rules)
• More consistent supernatant removal (no
longer depending on operator ability)
• “Washing” steps are more predictable
(time, supernatant quantity)
• product minimum loss during supernatant
removal (yield)
• Less solvent in the final product
• No delumping phase (better PSD)

26. Safety advantages
• Supernatant (flammable) manual removal
is avoided
• 2 wet product manual transfers are
avoided
• Nitrogen purging is never interrupted
• Nitrogen saving
• oxygen analyzer is no longer required
• 2 L.A.F. are avoided
• Lay out benefits