title: Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Drug and Food Control, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Mahjoubi
authors.affiliation: Department of Drug and Food Control, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Fazeli
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
authors.affiliation: Department of Drug and Food Control, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khoshayand
authors.affiliation: Research and Development Department, Zistdaru Danesh Company. Tehran, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Fazeli
authors.affiliation: Department of Drug and Food Control, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taghavian
authors.affiliation: Food and Drug Research Center, Food and Drug Organization, MOH&ME, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Rastegar
keywords: Aggregation; Box-Behnken experimental design; HSA-free formulation; Optimization; n-Dodecyl-β-D-maltoside
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