Arginine as a protein stabilizer and destabilizer in liquid formulations

Publication date: 20 November 2016 Source:International Journal of Pharmaceutics, Volume 513, Issues 1–2 Author(s): Nam Ah Kim, Sharvron Hada, Ritu Thapa, Seong Hoon Jeong Even though arginine monohydrochloride (ArgHCl) is a useful additive for protein stabilization, its mechanism is not yet fully elucidated. Moreover, there is a concern that ArgHCl may be a protein denaturant since it decreases transition melting temperature (Tm ) of certain proteins. It contains a guanidinium group, a critical structure for denaturating activity of guanidine hydrochloride (GndHCl). Effects of ArgHCl, GndHCl, and creatinine on a model protein, etanercept, were examined by biophysical analyses including DLS, DSC, FT-IR, microviscometer, and SEC. Accelerated storage stability of the protein was examined in the absence and presence of H2O2 at different incubation temperatures with pH monitoring. ArgHCl reduced protein aggregation and retained monomer, but increased fragmentation at high temperature. Tm 1 and Tm 2 of the protein increased with ArgHCl, but slight decrease (>1°C) in Tm 3 was observed. GndHCl and creatinine decreased all three Tm s. In the presence of heat and H2O2, the effect of ArgHCl was significantly decreased compared to GndHCl and creatinine. In addition, it accelerated the loss of monomer and increased fragmentation with decreasing pH. ArgHCl differed from GndHCl in the mode of physical interaction with the protein, due to its unique balance of three steric f...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research