Author:

Keywords:

Particle engineering, Spray drying, Monoclonal antibodies, Design of Experiments

Abstract:

INTRODUCTION & GOALS Spray drying (SD) was selected for converting monoclonal antibody (mAb) solutions into powders for reconstitution, which could increase mAb (storage) stability. The technique is able to yield readily dispersible powders, but addition of excipients is required to stabilise the mAbs during drying and subsequent storage 1, 2. Therefore, a large scale excipient screening was conducted to assess the impact of sugars, surfactant and amino acids (AAs) on mAb stability. METHODS mAB formulations were spray dried using a Büchi B-290 Mini Spray dryer, equipped with a two-fluid nozzle (0.7 mm internal diameter). Feed solutions contained the model mAb at a concentration of 50 mg/mL. For analysis, spray dried mAb powders were reconstituted to 100 mg/mL solutions. Moisture content was analysed using a Metrohm Titrino 831 Coulometer. Aggregation was assessed using a size exclusion chromatography (Tososh TSKgel G3000SWxl column) combined with multi-angle light scattering analysis (Wyatt miniDAWN TREOS), dynamic light scattering (Wyatt Möbius) and image analysis (Occhio ipac). RESULTS & DISCUSSION Addition of a non-ionic surfactant (polysorbate 20) to the formulation maintained the model mAb’s physical integrity during the SD process. Formulations containing a single AA, a combination of two AAs or their respective salts, were unable to adequately stabilise the mAb during 4 weeks of storage at 40°C, although basic AAs were found to stabilise the mAb to a greater extent than other tested AAs. Stability was further improved by combining these AAs with a disaccharide. CONCLUSION Formulations containing a basic AA, a disaccharide and a surfactant were found to have superior mAb stabilising properties compared to other tested formulations. However, further formulation optimisation is deemed necessary, as well as investigating interactions between excipients and identifying process parameters impacting mAb stability. REFERENCES 1. C. J. Roberts, Protein aggregation and its impact on product quality, Curr. Opin. Biotechnol.. 30 (2014) 211 – 217. 2. A. Ajmera, R. Scherließ, Stabilisation of proteins via mixtures of amino acids during spray drying, Int. J. Pharm. 463 (1) (2014) 98 – 107.