Adv Pharm Bull. 2015;5(4):497-505.
doi: 10.15171/apb.2015.068
PMID: 26819922
PMCID: PMC4729353
Scopus id: 84949655262
  Abstract View: 447
  PDF Download: 245

Original Research

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

Najmeh Mahjoubi 1, Mohammad Reza Fazeli 1 * , Rassoul Dinarvand 2, Mohammad Reza Khoshayand 1, Ahmad Fazeli 3 * , Mohammad Taghavian 1, Hossein Rastegar 4

1 Department of Drug and Food Control, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
2 Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
3 Research and Development Department, Zistdaru Danesh Company. Tehran, Iran.
4 Food and Drug Research Center, Food and Drug Organization, MOH&ME, Tehran, Iran.

Abstract

Purpose: Aggregation suppressing additives have been used to stabilize proteins duringmanufacturing and storage. Interferonβ-1b is prone to aggregation because of being nonglycosylated.Aggregation behavior of albumin-free formulations of recombinant IFNβ-1bwas 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 affectingaggregation in solutions. Box-Behnken technique was used to optimize the bestconcentration of additives and protein.Results: Quadratic model was the best fitted model for particle size, OD350 andOD280/OD260. The optimal conditions of 0.2% n-Dodecyl-β-D-maltoside, 70 mMarginine, 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, arginineand trehalose would demonstrate a significant stabilizing and anti-aggregating effect on theliquid formulation of interferonβ-1b. It can not only reduce the manufacturing costs but willalso ease patient compliance.
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