In-vial printing and drying of biologics as a personalizable approach

Abstract

This study addressed the need for a flexible (personalizable) production of biologics, allowing their stabilization in the solid state and processing of small batch volumes. Therefore, inkjet printing into vials followed by a gentle vacuum drying step at ambient temperature was investigated by screening different formulations with a 22-full factorial design of experiments regarding printability. Human Serum Albumin (HSA) was used as a model protein in a wide range of concentrations (5 to 50 mg/ml), with (10 w/v%) and without the surfactant polysorbate 80 (PS80). PS80 was identified to positively affect the formulations by increasing the Ohnesorge number and stabilizing the printing process. The dispensed volumes with a target dose of 0.5 mg HSA were dried and analyzed concerning their residual moisture (RM) and protein aggregation. All investigated formulations showed an RM < 10 wt% and no significant induced protein aggregation as confirmed by Size Exclusion Chromatography (<2.5%) and Dynamic Light Scattering (Aggregation Index ≤ 2.5). Additionally, long-term printability and the available final dose after reconstitution were investigated for two optimized formulations. A promising formulation providing ∼93% of the targeted dose and a reconstitution time of 30 s was identified.