Author/Authors :
Mahjoubi، Najmeh نويسنده Department of Drug and Food Control, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. , , FAZELI، MOHAMMAD REZA نويسنده , , Dinarvand، Rassoul نويسنده , , KHOSHAYAND، Mohammad Reza نويسنده , , fazeli Shooroki، Ahmad ali نويسنده Educational Planning, Khorasgan Branch, Islamic Azad University, Khorasgan, Iran , , Taghavian، Mohammad نويسنده Department of Drug and Food Control, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. , , Rastegar، Hossein نويسنده ,
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.
