Formation of insoluble particulates in a spray-dried F(ab')(2) fragment.

Abstract:

:An F(ab')2 fragment of an IgG has been spray-dried on a bench-top machine to examine the presence of insoluble particulates in the redissolved powder product. Preliminary experiments showed that treatment of the F(ab')2 in aqueous solution in a water bath at 65°C for 1 h produced fragmentation and also insoluble particulates, but no alteration in soluble aggregates. On spray drying, there was, however, no fragmentation but rather formation of soluble aggregates and insoluble particulates. There is therefore a strong difference between isothermal heat-induced damage in solution and during spray drying. The insoluble particulates were detected using a particle counter as a number distribution that was converted to a weight distribution. Addition of trehalose to the liquid feed strongly reduced the formation of the insoluble particulates, indicating that these are insoluble aggregates of the protein and not particulate contamination from the spray dryer. Trehalose (100 mM) was required to suppress formation of the insoluble aggregates, whereas 10 mM was sufficient to prevent formation of soluble aggregates. The particle counter and also isoelectric focusing gave consistent detection of the insoluble particles, whereas photon correlation spectroscopy gave inconsistent results. Spray-drying of small volumes of liquid feed on the bench-top scale can be performed without introducing nonproteinaceous insoluble particulates.

journal_name

J Pharm Sci

authors

Lassner P,Adler M,Lee G

doi

10.1002/jps.23891

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

1021-31

issue

4

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)30637-7

journal_volume

103

pub_type

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