Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation
Purpose: Aggregation suppressing additives have been used to stabilize proteins during manufacturing and storage. Interferonβ-1b is prone to aggregation because of being non-glycosylated. Aggregation behavior of albumin-free formulations of recombinant IFNβ-1b was explored using additives such as n-...
Main Authors: | , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Tabriz University of Medical Sciences
2015-11-01
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Series: | Advanced Pharmaceutical Bulletin |
Subjects: | |
Online Access: | http://journals.tbzmed.ac.ir/APB/Manuscript/APB-5-497.pdf |
Summary: | Purpose: Aggregation
suppressing additives have been used to stabilize proteins during manufacturing
and storage. Interferonβ-1b is prone to aggregation because of being
non-glycosylated. Aggregation behavior of albumin-free formulations of
recombinant IFNβ-1b was explored using
additives such as n-dodecyl-β-D-maltoside, Tween 20, arginine, glycine,
trehalose and sucrose at different pH.
Methods: Fractional factorial design was applied to
select major factors affecting aggregation in solutions. Box-Behnken technique
was used to optimize the best concentration of additives and protein.
Results: Quadratic model was the best fitted model for
particle size, OD350 and OD280/OD260. The optimal conditions of 0.2%
n-Dodecyl-β-D-maltoside, 70 mM arginine, 189 mM trehalose and protein
concentration of 0.50 mg/ml at pH 4 were achieved. A potency value of 91% ± 5% was obtained for the optimized formulation.
Conclusion: This study shows that the combination of
n-Dodecyl-β-D-maltoside, arginine and trehalose would demonstrate a significant
stabilizing and anti-aggregating effect on the liquid formulation of
interferonβ-1b. It can not only reduce the manufacturing costs but will also
ease patient compliance. |
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ISSN: | 2228-5881 2251-7308 |