Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation

Advanced Pharmaceutical Bulletin
Najmeh MahjoubiHossein Rastegar

Abstract

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. 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. 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. 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.

References

Aug 26, 1999·International Journal of Pharmaceutics·W Wang
Mar 15, 2000·Protein Science : a Publication of the Protein Society·D SamuelC Yu
May 8, 2001·Annual Review of Biophysics and Biomolecular Structure·P R Davis-SearlesG J Pielak
Oct 2, 2004·Biotechnology Progress·Kouhei TsumotoTsutomu Arakawa
Jan 18, 2005·International Journal of Pharmaceutics·Wei Wang
Apr 2, 2005·Nature Reviews. Drug Discovery·Sven Frokjaer, Daniel E Otzen
May 17, 2005·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Stéphanie PassotMichèle Marin
Jan 30, 2007·Biophysical Chemistry·Tsutomu ArakawaSerge N Timasheff
Jun 19, 2007·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Andrea Hawe, Wolfgang Friess
Sep 25, 2007·The Journal of Physical Chemistry. B·Milton T Sonoda, Munir S Skaf
Jun 13, 2009·Current Pharmaceutical Biotechnology·Christian Lange, Rainer Rudolph
Jun 13, 2009·Current Pharmaceutical Biotechnology·Makoto NakakidoKouhei Tsumoto
Jun 10, 2010·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Robert A RifkinMichael Levy
Oct 12, 2010·The Journal of Physical Chemistry. B·Diwakar Shukla, Bernhardt L Trout
Nov 5, 2010·Life Sciences·Laishram R SinghFaizan Ahmad
Dec 29, 2010·The Journal of Physical Chemistry. B·Liel Sapir, Daniel Harries
May 17, 2011·The Journal of Physical Chemistry. B·Curtiss P SchneiderBernhardt L Trout
Jul 19, 2011·Advanced Drug Delivery Reviews·Diwakar ShuklaBernhardt L Trout
Nov 28, 2012·Journal of Biotechnology·Ahmad FazeliAli Akbar Moosavi-Movahedi
Jun 24, 2014·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Mohadeseh Haji AbdolvahabHuub Schellekens
Aug 22, 2014·AAPS PharmSciTech·Ahmad FazeliMohammad Reza Fazeli
Dec 11, 2014·Journal of Pharmaceutical Sciences·Tiina LipiäinenAnne Juppo

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.