The use of amino acids to prepare physically and conformationally stable spray-dried IgG with enhanced aerosol performance.

This study investigated the effect of various amino acids on the molecular and thermodynamic stability of IgG (immune globulin G) as well as its aerosol performance. The antibody was spray-dried in the presence of different amino acids (leucine, phenylalanine, cysteine, glycine, lysine and arginine) using 20% and 50% (w/w) amino acid. SEC-HPLC, SDS-PAGE and IR-spectroscopy were performed to evaluate the stability of spray-dried IgG. The in-vitro aerosol performance of the well-stabilized formulations was subsequently assessed. IgG containing phenylalanine at 20 and 50% w/w produced the lowest content of aggregated antibody (1.35 ± 0.24%) and (1.12 ± 0.15%). The application of phenylalanine and cysteine at 50% (w/w) demonstrated the best storage stability (2 month at 45°C) with a rate constant of 0.006/month and enhanced fine particle fractions of 62.43 ± 0.34% and 70.51 ± 0.23%, respectively. Samples containing 50% arginine exhibited significantly perturbed conformation and, consequently, the highest aggregation rate constant of 0.019/month following storage. These results indicate that phenylalanine and cysteine serve as efficacious amino acids for the preparation of IgG dry powder with regard to stability and aerodynamic properties.