Particle Size Distribution Comparison
Spray Drying
|
Case Study #1
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Case Study #2
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Case Study #3
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Case Study #4
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| Buchi-290 | 12.6 µm | 5.0 µm | 5.9 µm | 8.11 µm |
| CritiTech SD30 (cGMP Phase I & II) |
9.6 µm | 3.9 µm | 5.0 µm | 6.87 µm (Methanol) 6.89 µm (Water) |
- Distribution spread is calculated by subtracting the Dv10 from the Dv90.
- In every case, the CritiTech SD30 produced similar particles to the Buchi-290 but with a narrower distribution.
Production Rate Increase
Compound A |
Solvent |
Feed Concentration |
Feed Rate |
Production Rate Increase |
| Buchi B-290 | Dichloromethane | 2 % | 5 ml/min |
9.5x |
| CritiTech SD30 | 47.5 ml/min |
Kollidon® VA64 |
Solvent |
Feed Concentration |
Feed Rate |
Production Rate Increase |
| Buchi B-290 | Methanol | 10 % | 8.2 ml/min |
5.5x |
| CritiTech SD30 | 45 ml/min |
Dexolve™– 7 |
Solvent |
Feed Concentration |
Feed Rate |
Production Rate Increase |
| Buchi B-290 | Methanol | 2.7 % | 14 ml/min |
3.2x |
| CritiTech SD30 | 45 ml/min |
Kollidon® 17 PF |
Solvent |
Feed Concentration |
Feed Rate |
Production Rate Increase |
| Buchi B-290 | Acetone | 4 % | 16 ml/min |
1.9x |
| CritiTech SD30 | 30 ml/min |
Notes
1.Production runs were designed to reproduce material not to maximize the production rate.
2.Another product has been processed with the SD30 in dichloromethane at a feed rate of 135 ml/min or 10.8 kg/hr.
Spray Drying Scale-Up Case Study #1 – Compound A
- Customer’s target product profile was D50 <10 μm and as close to 5 μm as possible.
- Feasibility testing conducted using the Buchi B-290.
- Scale-up testing and manufacturing conducted on the CritiTech SD30.
- D50 of 4.49 to 12.2 μm were produced.
Compound A – SD30 Scale-up runs
| Dv10 | 3.32 | 5.15 | 0.759 | 0.848 | 0.821 | 0.645 |
| Dv50 | 8.61 | 12.2 | 4.99 | 4.94 | 5.05 | 4.49 |
| Dv90 | 23.5 | 24.4 | 36 | 11.1 | 12.3 | 10.2 |
The larger capacity SD30 (cGMP Manufacturing Unit) produced spray-dried material consistent with the material produced on the Buchi B-290, at a production rate of 9.5x.
Buchi B-290(POC Unit) |
CritiTech SD30(cGMP Phase I & II Unit) |
|
| D10 (µm) | 4.20 | 0.65 |
| D50 (µm) | 9.30 | 4.49 |
| D90 (µm) | 16.80 | 10.20 |
XRPD
Comparison of Buchi-290 and CritiTech SD30
Production Yield Comparison
Spray Drying Equipment |
Number of Runs |
Average Yield |
| Buchi-290 | 11 | 73% |
| CritiTech SD30 | 12 | 70% |
70% production yield on the SD30 was observed for “Compound A.” Yield would likely have been higher if a larger mean particle size was requested by the customer. Nevertheless, the SD30’s yield was very similar to yields observed on the Buchi-290, but with smaller and more narrow particle size distribution.
As with any spray drying equipment, the production yield can vary substantially depending on the target product profile and processing parameters.
Spray Drying Case Study #2 – Kollidon® 17 PF
Kollidon® 17 PF
PVP-based solubilizer for parenteral and oral formulations1
Hydrophilic crystallization inhibitor
1. “Kollidon 17 PF.” Excipients for Drug Formulation, BASF, pharmaceutical.basf.com/en/Drug-Formulation/Kollidon-17-PF.html.
Buchi B-290 (POC Unit) |
CritiTech SD30 (cGMP Phase I & II Unit) |
|
| D10 (µm) | 0.779 | 0.777 |
| D50 (µm) | 2.53 | 2.17 |
| D90 (µm) | 5.73 | 4.65 |
Spray Drying Case Study #3 – Kollidon® VA 64
Kollidon® VA 64
PVP-based excipient used in granulation as a dry binder and as a film-forming agent in tablet coatings and topical sprays
Buchi B-290 (POC Unit) |
CritiTech SD30 (cGMP Phase I & II Unit) |
|
| D10 (µm) | 0.342 | 0.426 |
| D50 (µm) | 2.94 | 2.13 |
| D90 (µm) | 6.20 | 5.46 |
Spray Drying Case Study #4 – Dexolve™
Dexolve-7TM
Sulfobutyl Ether β-Cyclodextrin Sodium (SBECD) excipient for enhanced bioavailability and improved pharmaceutical formulations.
Buchi B-290
|
CritiTech SD30
|
CritiTech SD30
|
|
| D10 (µm) | 1.43 | 1.77 | 1.21 |
| D50 (µm) | 4.57 | 4.28 | 3.49 |
| D90 (µm) | 9.54 | 8.64 | 8.10 |
System |
Solvent |
Concentration |
Feed Rate |
Production Rate |
Rate Increase |
| Buchi B-290 | Methanol | 2.7 % | 14 ml/min | 0.378 g/min | NA |
| CritiTech SD30 | Methanol | 2.7 % | 45 ml/min | 1.215 g/min |
3.2x |
| CritiTech SD30 | Water | 15.32 % | 31.5 ml/min | 4.826 g/min |
12.8x |
The DexolveTM particle size distribution produced on the Buchi B-290 was was reproduced using the SD30 at a 3.2x production rate increase with the methanol system and 12.8x increase in the water system. Higher production rate increases is expected with further process optimization.