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Spray Drying of Proteins Geoffrey Lee

Spray Drying of Proteins Geoffrey 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.

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Spray Drying of Proteins Geoffrey Lee

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  1. 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.

  2. 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 (66:33) • Example III: peptide 1.7 kDa - monomer: 98.54  98.51 on SD at 130oC/95oC

  3. 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

  4. 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

  5. Dynamic adsorption kinetics of trypsinogen at air/water-interface After 1s  = 14 – 19 mg/m2 Assumption: Gibbs adsorption isotherm holds !

  6. Surface composition of spray dried trehalose/BSA (95:5)

  7. Effects of polysorbyte 80 on surface composition of spray dried trehalose/BSA (95:5)

  8. Single droplet drying levitator Acknowledgement: Niro Copenhagen !

  9. Single droplet drying levitator

  10. 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 = /358 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 !

  11. Single-droplet drying kinetics of trehalose (10%)

  12. Single-droplet drying kinetics of trehalose (10%) I II III IV

  13. Single-droplet drying kinetics of trehalose (10%)

  14. Single-droplet drying kinetics of BSA (10%)

  15. Single-droplet drying kinetics of treh/BSA (9:1) (10%)

  16. Constant-rate drying period: d2 law sphere; T constant; no convection;saturtated 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]

  17. Constant-rate drying period: evaporation coefficients & the problem of droplet surface temperature

  18. Constant-rate drying period: evaporation coefficients & Sherwood number

  19. 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. www.pharmtech.uni-erlangen.de

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