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Surface characterisation of freeze-dried protein/carbohydrate mixtures

Millqvist-Fureby, Anna LU ; Malmsten, Martin LU and Bergenståhl, Björn LU orcid (1999) In International Journal of Pharmaceutics 191(2). p.103-114
Abstract

In the present investigation freeze-drying of proteins (BSA or trypsin) together with various carbohydrates, i.e. lactose, sucrose, mannitol, α-cyclodextrin and dextrin, has been studied with particular emphasis on the surface composition of the freeze-dried powders. The proteins were found to be over-represented on the powder surface as compared to the bulk concentration of protein. The mechanism behind the surface accumulation is believed to be that proteins adsorb preferentially over carbohydrates to the ice/liquid interface in the frozen sample. The degree of surface accumulation depended on the carbohydrate used, and was increased in annealed samples compared to reference samples. The activity of trypsin was fairly well preserved... (More)

In the present investigation freeze-drying of proteins (BSA or trypsin) together with various carbohydrates, i.e. lactose, sucrose, mannitol, α-cyclodextrin and dextrin, has been studied with particular emphasis on the surface composition of the freeze-dried powders. The proteins were found to be over-represented on the powder surface as compared to the bulk concentration of protein. The mechanism behind the surface accumulation is believed to be that proteins adsorb preferentially over carbohydrates to the ice/liquid interface in the frozen sample. The degree of surface accumulation depended on the carbohydrate used, and was increased in annealed samples compared to reference samples. The activity of trypsin was fairly well preserved (58-90%) in the freeze-dried powders, but depended on the carbohydrate excipient, whilst the surface composition had little effect on the activity. The activity preservation was improved when the protein concentration was raised from 1 to 10% in the solids. The surface composition of powders containing mixtures of mannitol and dextrin as excipients depended on the ratio between the two carbohydrates, with the lowest surface coverage of protein obtained in 50/50 mixtures. Copyright (C) 1999 Elsevier Science B.V.

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Please use this url to cite or link to this publication:
author
; and
publishing date
type
Contribution to journal
publication status
published
keywords
BSA, ESCA, Freeze-drying, Surface analysis, Trypsin
in
International Journal of Pharmaceutics
volume
191
issue
2
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:0032744304
  • pmid:10564837
ISSN
0378-5173
DOI
10.1016/S0378-5173(99)00285-9
language
English
LU publication?
no
id
9207b163-00d9-40be-9ed6-001e7a0c4f79
date added to LUP
2025-04-14 17:32:07
date last changed
2025-04-23 11:24:09
@article{9207b163-00d9-40be-9ed6-001e7a0c4f79,
  abstract     = {{<p>In the present investigation freeze-drying of proteins (BSA or trypsin) together with various carbohydrates, i.e. lactose, sucrose, mannitol, α-cyclodextrin and dextrin, has been studied with particular emphasis on the surface composition of the freeze-dried powders. The proteins were found to be over-represented on the powder surface as compared to the bulk concentration of protein. The mechanism behind the surface accumulation is believed to be that proteins adsorb preferentially over carbohydrates to the ice/liquid interface in the frozen sample. The degree of surface accumulation depended on the carbohydrate used, and was increased in annealed samples compared to reference samples. The activity of trypsin was fairly well preserved (58-90%) in the freeze-dried powders, but depended on the carbohydrate excipient, whilst the surface composition had little effect on the activity. The activity preservation was improved when the protein concentration was raised from 1 to 10% in the solids. The surface composition of powders containing mixtures of mannitol and dextrin as excipients depended on the ratio between the two carbohydrates, with the lowest surface coverage of protein obtained in 50/50 mixtures. Copyright (C) 1999 Elsevier Science B.V.</p>}},
  author       = {{Millqvist-Fureby, Anna and Malmsten, Martin and Bergenståhl, Björn}},
  issn         = {{0378-5173}},
  keywords     = {{BSA; ESCA; Freeze-drying; Surface analysis; Trypsin}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{2}},
  pages        = {{103--114}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Pharmaceutics}},
  title        = {{Surface characterisation of freeze-dried protein/carbohydrate mixtures}},
  url          = {{http://dx.doi.org/10.1016/S0378-5173(99)00285-9}},
  doi          = {{10.1016/S0378-5173(99)00285-9}},
  volume       = {{191}},
  year         = {{1999}},
}