Pharmaceutical Technology - May 2018

Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing

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22 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m surements, which resulted in a large confidence interval that enveloped all other impeller test cases. Both up-pumping A340 configurations provided more consistent blend time performance than the down-pumping configurations. When the agitator was removed, leaving the bubble column to gener- ate f luid motion, blend time increased by no less than 50% and was statistically significant. The mass transfer test results were compiled and are shown in Figure 3. The dual down-pumping A320s established a base case mean k L a 20 of 9–10 inverse hours. Halv- ing the power input of the dual A320 impeller configuration reduced the mean k L a 20 to between eight and nine inverse hours. When the power input was maintained but the gas f low rate was halved, the mean k L a 20 fell to a range of 4–6 in- verse hours, which was approximately half of the base case mean k L a 20 . The results aligned with theoretical expectations based on Equation 2 and Bioreactor Design Table II: Impeller configurations and operating conditions for experimental cases. P/V is agitator power input per unit volume. ACFH is actual cubic feet per hour (the air flow rate seen by the impeller closest to the sparge). VVM is vessel volume per minute. Test case 1 2 3 4 5 6 7 Description Dual down Half power Half gas Gas only Single down Dual up Triple up Impeller type A320 A320 A320 N/A A320 A340 A340 Impeller quantity 2 2 2 0 1 2 3 Impeller diameter (D) [in] 7 7 7 N/A 7 7 7 D/Tank diameter (T) 0.40 0.40 0.40 N/A 0.40 0.40 0.40 Impeller off-bottom (C) [in] 5 5 5 N/A 5 5 5 C/D 0.71 0.71 0.71 N/A 0.71 0.71 0.71 Impeller spacing (S) [in] 10 10 10 N/A N/A 14 7.4 S/D 1.43 1.43 1.43 N/A N/A 2.00 1.06 Speed (N) [rpm] 174 139 174 0 215 174 155 P/V [HP/kgal] 0.4 0.2 0.4 0 0.4 0.4 0.4 Gas flow rate (Q) [ACFH] 16.6 16.6 8.3 16.6 16.6 16.6 16.6 f [ft/min] 0.17 0.17 0.09 0.17 0.17 0.17 0.17 VVM [1/min] 0.10 0.10 0.05 0.10 0.10 0.10 0.10 Figure 2: Mean blend time with 95% confidence intervals. Figure 3: Mean k L a 20 with 95% confidence intervals. Dual Down Half Power Half Gas Gas Only Single Down Dual Up Triple Up Blend Time (s) 0 5 10 15 20 25 Dual Down Half Power Half Gas Gas Only Single Down Dual Up Triple Up k L a 20 (1/hr) 0 5 10 15

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