title: The use of amino acids to prepare physically and conformationally stable spray-dried IgG with enhanced aerosol performance.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Homa
authors.initials: H
authors.lastname: Faghihi
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: vatanara@tums.ac.ir.
authors.forename: Alireza
authors.initials: A
authors.lastname: Vatanara
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abdolhosein Rouholamini
authors.initials: AR
authors.lastname: Najafabadi
authors.affiliation: Faculty of Pharmacy, Shahid Sadoqi University of Medical Science, Yazd, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Ramezani
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Gilani
mesh_terms: D000336:Aerosols; D000596:Amino Acids / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D007074:Immunoglobulin G / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D033362:Powder Diffraction; D011487:Protein Conformation; D014961:X-Ray Diffraction
chemical_list: D000336:Aerosols; D000596:Amino Acids; D007074:Immunoglobulin G
keywords: Aerosol performance; Amino acid; IgG; Spray drying; Stability