TABLE IX
Comparison of the Mixer Models in SvP Formation in mAb A Formulation
| Mixing/Measuring System | Rotating Cylinder | Stationary Cylinder | Gap (mm) | Rotational Speed (rpm) | Tip Speed (m/s) | Sample Volume (L) | Shear (S−1) | Surface-Area-to-Volume Ratio (m2/L) | Particle Count (1/mL) by Coulter Counter (1.18–30 μm) | Change in SvP Relative to t = 0a | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Before Rotation | After 1 h Rotation | ||||||||||
Impeller/Drive Unit Coupling (Mavag Mavadrive™ Mixer) | Impeller | Drive Unit (Radius: 8 mm) | 0.035-0.040 | 200 | 0.84 | 2.5000 | 4798 | 0.001b | 1.45 × 104 ± 4.08 × 103 | 5.03 × 105 ± 2.77 × 104 | 35 |
Double-Gap Rheometer | R2 = 12.329 mm R3 = 13.329 mm | R1 = 11.910 mm R4 = 13.798 mm | G1 = 0.419 G4 = 0.469 | 660 | 0.92 | 0.0038 | 2000 | 3.632c | 3.09 × 103 ± 2.86 × 102 | 5.19 × 103 ± 4.38 × 103 | 2 |
Cone-Plate Rheometer | Cone diamter = 60 | Bottom plate | 0.018 (tip of the cone) | 436 | 1.37 | 0.0300 | 2612 | 0.094 | 2.03 × 104 ± 1.02 × 104 | 1.43 × 105 ± 2.13 × 104 | 7 |
Plate-Plate Rheometer | Top plate diamter = 40 | Bottom plate | 0.100 | 654 | 1.37 | 0.0300 | 13700 | 0.042 | 2.03 × 104 ± 1.02 × 104 | 1.10 × 105 ± 5.95 × 104 | 5 |
↵a Change in SvP relative to t = 0: average particle count after mixing for 1 h rotation ÷ average particle count in mAb A at t = 0 (before rotation).
↵b Surface area of the ceramic bearing of the drive unit (1 cm radius and 2 cm length) × 2 surfaces/sample volume (2.5 L).
↵c Combined surface area of rotational cylinder (cup) and stationary cylinder (inner surface area of the outer stationary cylinder + outer surface area of the cup + outer surface area of the inner stationary cylinder + inner surface area of the inner stationary cylinder) × length of the cup (4.2 cm)/sample volume (3.8 mL).