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Application Notes
A new means to optimizing the drying step
and eliminating failed batches
as presented by Kevin Girard
Bristol-Myers Squibb Company
at Lasentec® Users’ Forum 2002 - Charleston
Pharmaceutical product quality can be greatly affected by attrition in the
filter-cake step following crystallization. Dryer performance is normally
evaluated with dissolution testing of the final product, which can
sometimes take weeks. Because a Lasentec® D600L (FBRM® technology)
had been used to monitor the prior crystallization step, chemists decided to
use FBRM® to examine the effect of drying as well.
The dried product was immersed in a solvent so that FBRM® could monitor
it as a slurry. Careful attention was paid to sample size, type of solvent,
and equilibrium time in order to minimize discrepancy between FBRM®
characterization of these samples and characterization of the original wet
filter cake.
The FBRM® square-weighted median statistic was used to track the
population and dimension of coarse crystals in the system (Figure 1).
FBRM® successfully correlated dryer performance to drug performance.
Low shear was found to cause less attrition than high shear, and filter
drying resulted in less attrition than tumble drying.
Percent particles sized X (-0.5 to 3.5)
Application Notes
Original wet cake SQM = 76.42
Low shear filter dried SQM = 76.34
Low shear tumble dried SQM = 75.33
Conical dried SQM = 59.71
High shear filter dried SQM = 34.48
High shear tumble dried SQM = 40.54
Pin milled SQM = 25.48
Size, microns (1 to 1000)
Figure 1: FBRM® data indicates that low-shear filter drying causes the least attrition
FBRM® successfully quantified the effect of dryer type and shear on
product quality, and these results were used to develop a new dryer
protocol that minimized the amount of crystal breakage. No failed batches
occurred after the new low-shear dryer protocol was implemented.
Mettler-Toledo
Mettler-Toledo Xxxxx
AutoChem, Inc.
Address
7075 Samuel Morse Drive
Address
Columbia, MD 21046 USA
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Tel: +1 410 910 8500
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Fax: +1 410 910 8600
Email: [email protected]
M-2-144 Rev E (03/2006) Printed in USA
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