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Scale-up methodology
Feed atomization
produces small
droplets
with the target
size distribution
Dry product
collection
Thermodynamics
• to calculate of RS_out, T_dew, dgas
hot drying gas
• detect abnormal conditions of operation
Feed • a tool for development & scale-up
Gas
Tank
Recycling
wet gas Unit
Drying chamber
Cyclone Atomization
• a tool for scale-up
• to achieve target particle size distribution
hot drying gas
Gas
Recycling
Unit
Drying Kinetics
wet gas
Drying chamber
Cyclone
Product
• to control particle morphology
(very fine particles) • to optimize powder performance
• identify pitfalls
Product
(very fine particles)
4 | João Vicente | April 2014 | Confidential Hovione © 2014
Thermodynamics
• Thermal conditions in a spray dryer are determined through heat and mass
balance so that Qin Qfeed Qloss Qout
Qin FdryingTin Cp
i
g
i
g
i
+10%
160
T_in (predicted)
-10%
120
• Fast drying promotes the production of spherical particles; Slow drying results in the
production of shriveled particles; Solids concentration impacts shell flexibility
• Drying time depends on relative saturation and droplet size
• Bulk density is typically dependent on RS_out
Scale-up methodology
Feed properties
• Feed chemical and physical stability
• Solvent system, concentration, viscosity, etc...
Product attributes
• Stickness, tendency to agglomerate
• Residual solvents
• Chemical/physical stability, hygroscopicity, etc…
Process:
• Edge of failure
• Reprocessability Where everything starts!
• Process yield
• Ability to post-dry the SD powders
13 | João Vicente | April 2014 | Confidential Hovione © 2014
Setting a stable lab scale process
Solution stability - Temperature
m (cP)
T_feed
(ºC)
C_feed (%)
Set a process stable at lab conditions (assure good atomization and select
adequate T_in, T_out)
Select C_feed to maximize throughput but avoid very viscous solutions and keep
some distance from saturation.
Once the process seems stable, run it with extended processing time; check
the yield and the occurence of bearding problems
Use a close-loop system to get representative values for the residual solvents;
evaluate the feasibility of the solvent/post-drying step
Scale-up methodology
• The relation of Tg with RS_out enables the anticipation of the impact of the spray
drying operating conditions on the SDD amorphous stability
100
95 140
Droplet Size (mm)
80
100
75
70
80
65
60 60
55
50 40
30 40 50 60 70 80 90 100
Pressure (bar)
• Atomization issues
• Yield/agglomeration/stickness
• Bearding
• Chemical stability / degradation
• Solvent condensation
João Vicente
Drug Product Development
+351 21 982 9502
jvicente@hovione.com
www.hovione.com