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Protein spray-freeze drying. Effect of atomization conditions on particle size and stability.

Abstract：

PURPOSE:To investigate the effect of atomization conditions on particle size and stability of spray-freeze dried protein. METHODS:Atomization variables were explored for excipient-free (no zinc added) and zinc-complexed bovine serum albumin (BSA). Particle size was measured by laser diffraction light scattering following sonication in organic solvent containing poly(lactide-co-glycolide) (PLG). Powder surface area was determined from the N2 vapor sorption isotherm. Size-exclusion chromatography (SEC) was used to assess decrease in percent protein monomer. Fourier-transform infrared (FTIR) spectroscopy was employed to estimate protein secondary structure. PLG microspheres were made using a non-aqueous, cryogenic process and release of spray-freeze dried BSA was assessed in vitro. RESULTS:The most significant atomization parameter affecting particle size was the mass flow ratio (mass of atomization N2 relative to that for liquid feed). Particle size was inversely related to specific surface area and the amount of protein aggregates formed. Zinc-complexation reduced the specific surface area and stabilized the protein against aggregation. FTIR data indicated perturbations in secondary structure upon spray-freeze drying for both excipient-free and zinc-complexed protein. CONCLUSIONS:Upon sonication, spray-freeze dried protein powders exhibited friability, or susceptibility towards disintegration. For excipient-free protein, conditions where the mass flow ratio was > -0.3 yielded sub-micron powders with relatively large specific surface areas. Reduced particle size was also linked to a decrease in the percentage of protein monomer upon drying. This effect was ameliorated by zinc-complexation, via a mechanism involving reduction in specific surface area of the powder rather than stabilization of secondary structure. Reduction of protein particle size was beneficial in reducing the initial release (burst) of the protein encapsulated in PLG microspheres.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Costantino HR,Firouzabadian L,Hogeland K,Wu C,Beganski C,Carrasquillo KG,Córdova M,Griebenow K,Zale SE,Tracy MA

doi

10.1023/a:1007570030368

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

1374-83

issue

eissn

0724-8741

issn

1573-904X

journal_volume

pub_type

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Protein spray-freeze drying. Effect of atomization conditions on particle size and stability.