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Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on stability (I): stability of a monoclonal antibody.

Abstract：

:The present study was conducted to investigate the impact of drying method and formulation on the storage stability of IgG1. Formulations of IgG1 with varying levels of sucrose with and without surfactant were dried by different methods, namely freeze drying, spray drying, and foam drying. Dried powders were characterized by thermal analysis, scanning electron microscopy, specific surface area (SSA) analysis, electron spectroscopy for chemical analysis (ESCA), solid state FTIR, and molecular mobility measurements by both isothermal calorimetry and incoherent elastic neutron scattering. Dried formulations were subjected to storage stability studies at 40 degrees C and 50 degrees C (aggregate levels were measured by size exclusion chromatography initially and at different time points). Both drying method and formulation had a significant impact on the properties of IgG1 powders, including storage stability. Among the drying methods, SSA was highest and perturbations in secondary structure were lowest with the spray-dried preparations. Sucrose-rich foams had the lowest SSA and the lowest protein surface accumulation. Also, sucrose-rich foams had the lowest molecular mobility (both fast dynamics and global motions). Stability studies showed a log-linear dependence of physical stability on composition. Preparations manufactured by "Foam Drying" were the most stable, regardless of the stabilizer level. In protein-rich formulations, freeze-dried powders showed the poorest storage stability and the stability differences were correlated to differences in secondary structure. In stabilizer-rich formulations, stability differences were best correlated to differences in molecular mobility (fast dynamics) and total protein surface accumulation.

journal_name

J Pharm Sci

journal_title

Journal of pharmaceutical sciences

authors

Abdul-Fattah AM,Truong-Le V,Yee L,Nguyen L,Kalonia DS,Cicerone MT,Pikal MJ

doi

10.1002/jps.20859

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

1983-2008

issue

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)36301-8

journal_volume

pub_type

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Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on stability (I): stability of a monoclonal antibody.