Application of Disaccharides Alone and in Combination, for the Improvement of Stability and Particle Properties of Spray-Freeze Dried Igg Publisher Pubmed



Daneshmand B¹ ; Faghihi H¹ ; Amini Pouya M¹ ; Aghababaie S¹ ; Darabi M¹ ; Vatanara A¹ Show Affiliations
Source: Pharmaceutical Development and Technology Published:2019

Abstract

Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD. Methods: Induced soluble aggregates were quantified at 0 and 3 months, and 45 °C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy. Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12 µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage. Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.