Protein powders for encapsulation: a comparison of spray-freeze drying and spray drying of darbepoetin alfa.
OBJECTIVE
To evaluate spray-freeze drying and spray drying processes for fabricating micron-sized particles of darbepoetin alfa (NESP, Aranesp) with uniform size distribution and retention of protein integrity, requirements for encapsulation.


METHODS
Darbepoetin alfa was spray-freeze dried using ultrasonic atomization at 120 kHz and 25 kHz and spray dried at bench-top and pilot scales. Reconstituted powders were evaluated by size exclusion chromatography and UV/VIS spectroscopy. Powder physical properties were also characterized.


RESULTS
Spray-freeze drying resulted in aggregation of darbepoetin alfa. Aggregates (primarily insoluble) formed on drying and/or reconstitution. Particle size distributions were broad (span > or = 3.6) at both nozzle frequencies. Annealing before drying reduced aggregate levels slightly but increased particle size over 5-fold. Spray drying at inlet temperatures up to 135 degrees C (and outlet temperatures up to 95 degrees C) showed little impact on integrity. Integrity at bench-top and pilot scales was identical, with 0.2% dimer and no high molecular weight or insoluble aggregates detected. Particle size was small (< or = 2.3 microm) with uniform distribution (span < or = 1.4) at both process scales.


CONCLUSIONS
Under the conditions tested spray drying, conducted at bench-top and pilot scales with commercially available equipment, was superior to spray-freeze drying for the fabrication of darbepoetin alfa particles for encapsulation.
Nguyen
Xichdao C
XC
Pharmaceutics and Drug Delivery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA.
Herberger
John D
JD
Burke
Paul A
PA
D002626:Chemistry, Pharmaceutical; D000068256:Darbepoetin alfa; D003890:Desiccation; D005612:Freeze Drying; D010316:Particle Size; D011208:Powders / Q000737:chemistry
D011208:Powders; D000068256:Darbepoetin alfa