Info

Fig. 30.4. Scaling up and screening intensity.

Screening Intensity Number of Experiments

Single Parameter Set for (Pilot) Production

Fig. 30.4. Scaling up and screening intensity.

ferent modes (batch or continuously); typically, it is run in a miniplant and a pilot unit.

These two goals - optimization and scaling up - are largely independent of one another (Fig. 30.4)!

For example, even thousands of experiments carried out on a milligram scale cannot replace a pilot run. For an efficient process development, the "hits" from primary screening have to be followed up in another screen under more defined conditions and on a larger scale (''secondary screen''). Since a larger number of hits is expected from the primary screening, the secondary screening also needs a reasonable degree of parallelization (typically 1:5 to 1:100). The same holds for the tertiary screen.

Therefore, the typical picture of a pyramid results (Fig. 30.5), with decreasing numbers of reactions in consecutive screens. At the top, one optimal set of parameters is created and verified in a single representative and fully scalable reactor (parallelization 1).

For high efficiency in process development, the existing screens have to be combined and experiments have to be performed at the smallest relevant scale. It is crucial to check the results from earlier screens in the more precise later screens as soon as possible and to set up mass and mole balances to detect artifacts stemming from lack of scalability, errors in analysis, or a lack of reproducibility.

Accuracy/Scale

Typical Parallel Reactions Throughput

Accuracy/Scale

48-96

4-16

8-48

Fig. 30.5. Different phases in process development.

48-96

4-16

8-48

Workstations with dispenser, racks, analysis automation

Multiple reaction blocks (5-100 ml) with low to medium automation degree

Multiple 50-100 ml reactor stations, independent temperature control and dosage opportunities automation and online analysis

Single 1 L reactors with full dosage

Fig. 30.5. Different phases in process development.

Was this article helpful?

0 0

Post a comment