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Spray Drying of ProteinsGeoffrey Lee

• Spray drying (SD) of protein-containing systems
  is not new !
• Applications of SD of proteins - inhaleable
  powders - injectable powders - stable,
  flowable storage-form for bulk protein.
• Other considerations apply compared with freeze
  drying (FD) of proteins - effects of
  atomization of liquid feed - effects of thermal
  stress - question of dry powder yield.

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Feasibility of spray drying a protein

• Product quality (peptide/protein) investigated
  by - activity loss (enzymes) - change in
  aggregation status (HPLC, SEC) - alteration in
  FT-IR amide bands
• Formulation measures - disaccharides to improve
  process and/or storage stability (sorbitol
  versus trehalose) - residual moisture Tg
  measurements
• Example I model protein trypsinogen (Tzannis
  Prestrelski, 1999) - ca 15 activity loss on SD
  at Tin/Tout 110oC/70oC - ca 20 loss of
  monomer (SEC)
• Example II IgG (AMG162) (Maury et al, 2004) -
  ca 15 increase in total aggregates on SD at
  130oC/90oC - reduced to 1 increase with
  IgG/sorbitol (6633)
• Example III peptide 1.7 kDa - monomer 98.54 ?
  98.51 on SD at 130oC/95oC

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Potential sources of protein damage
Drying air
2. Shearing forces
Nozzle
Atomizing air
1. Adsorption
Liquid feed
3. Liquid/air interface expansion
4. Thermal stress
Drying tower
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The 2 periods of droplet drying
Various morpholgies
Critical point
Constant-rate phaseT approx. Twetbulb
Falling-rate phase T ? Toutlet
Residence time 1s 25s
eg, Tinlet/Toutlet 130oC/90oC
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Dynamic adsorption kinetics of trypsinogen at
air/water-interface
After 1s ? 14 19 mg/m2
Assumption Gibbs adsorption isotherm holds !
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Surface composition of spray dried trehalose/BSA
(955)
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Effects of polysorbyte 80 on surface composition
of spray dried trehalose/BSA (955)
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Single droplet drying levitator
Acknowledgement Niro Copenhagen !
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Single droplet drying levitator
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Single droplet drying levitator

• Variable drying air temperature humidity
• 2. Droplet size can be varied in ultrasonic
  field largest levitatable D 2/3 ? optimal D
  ?/3 58 kHz levitator (?amb 5.9 mm) 2500 15
  µm
• 3. Relative velocity conditions
  (droplet/drying air) ? during SD, ?rel is low
  for most of residence time Red (droplet/air) ?
  1000
• ? much higher in droplet deceleration
  phase Red in levitator chamber adjustable via
  ?
• D mm Red (max) Uair (max)
• 0.895 849 682
• 0.985 912 666
• 1.060 960 651
• (Source Yarin A, et al., Phys. Fluids, 9,
  3300-3314 (1997)) ? at very low ?rel, boundary
  layer theory applicable Nu Sh 2
  questionable because of acoustic steaming !

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Single-droplet drying kinetics of trehalose (10)
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Single-droplet drying kinetics of trehalose (10)
I
II
III
IV
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Single-droplet drying kinetics of trehalose (10)
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Single-droplet drying kinetics of BSA (10)
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Single-droplet drying kinetics of treh/BSA (91)
(10)
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Constant-rate drying period d2 law
sphere T constant no convectionsaturtated pv
at surface stready state vapor diffusion
1.0
r(t)2/r02
-?v ?m2/s
0
t/r02 s/?m2
?v Evaporation coefficient µm2/s
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Constant-rate drying period evaporation
coefficients the problem of droplet surface
temperature
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Constant-rate drying period evaporation coefficie
nts Sherwood number
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SPRAY DRYING OF PROTEINS

• Damage to proteins can occur in both phasesof
  droplet drying - constant rate phase large ?
  in ms frame - falling-rate phase thermal
  effects.
• Single-droplet drying levitator can be used
  toexamine particle formation in real time -
  shows build-up of particle morphology - gives
  continual measure of momentary drying rate
  before after critical point.

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