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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 Address Tel: +1 410 910 8500 Address Fax: +1 410 910 8600 Email: [email protected] M-2-144 Rev E (03/2006) Printed in USA www.mt.com/lasentec www.mt.com Visit for more information