title: Protein spray freeze drying. 2. Effect of formulation variables on particle size and stability.
abstract: Spray freeze drying produces protein particles suitable for microencapsulation into polymeric microspheres intended for sustained release. Accessibility of encapsulated protein particles to the microsphere surface increases as the protein particle size is increased. Thus, it is desirable that the encapsulated protein particle size be minimized to limit initial release. We have investigated the effect of formulation on spray freeze-dried bovine serum albumin (BSA) as a model protein. Atomization conditions were fixed such that in the absence of excipient, the particle size of the sonicated powder was submicron, and there was substantial protein degradation (loss of monomer). Addition of low concentrations of surfactants (up to the CMC) or mannitol (up to the point where it tended to crystallize upon dehydration) resulted in partial stabilization without impacting particle size. Trehalose was successful in stabilizing the protein; however, there was a marked increase in particle size at the highest levels tested. Ammonium sulfate provided partial stabilization, but also tended to form crystals and increase particle size. FTIR measurements showed a loss of native secondary structure upon spray freeze drying that was ameliorated by addition of trehalose. Other excipients did not prevent structural perturbations. In general, stabilization of spray freeze-dried BSA was related to lowering of the specific surface area in the powder. A balance must be achieved when spray freeze drying proteins intended for encapsulation in sustained-release systems.
authors.affiliation: Alkermes, Inc., 64 Sidney Street, Cambridge, Massachusetts 02139, USA. rick.constantino@alkermes.com
authors.forename: Henry R
authors.initials: HR
authors.lastname: Costantino
authors.forename: Laleh
authors.initials: L
authors.lastname: Firouzabadian
authors.forename: Chichih
authors.initials: C
authors.lastname: Wu
authors.forename: Karen G
authors.initials: KG
authors.lastname: Carrasquillo
authors.forename: Kai
authors.initials: K
authors.lastname: Griebenow
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Zale
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tracy
mesh_terms: D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins