title: Scalable organic solvent free supercritical fluid spray drying process for producing dry protein formulations.
abstract: In this study, we evaluated the influence of supercritical carbon dioxide (scCO2) spray drying conditions, in the absence of organic solvent, on the ability to produce dry protein/trehalose formulations at 1:10 and 1:4 (w/w) ratios. When using a 4L drying vessel, we found that decreasing the solution flow rate and solution volume, or increasing the scCO2 flow rate resulted in a significant reduction in the residual water content in dried products (Karl Fischer titration). The best conditions were then used to evaluate the ability to scale the scCO2 spray drying process from 4L to 10L chamber. The ratio of scCO2 and solution flow rate was kept constant. The products on both scales exhibited similar residual moisture contents, particle morphologies (SEM), and glass transition temperatures (DSC). After reconstitution, the lysozyme activity (enzymatic assay) and structure (circular dichroism, HP-SEC) were fully preserved, but the sub-visible particle content was slightly increased (flow imaging microscopy, nanoparticle tracking analysis). Furthermore, the drying condition was applicable to other proteins resulting in products of similar quality as the lysozyme formulations. In conclusion, we established scCO2 spray drying processing conditions for protein formulations without an organic solvent that holds promise for the industrial production of dry protein formulations.
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, The Netherlands.
authors.forename: O
authors.initials: O
authors.lastname: Nuchuchua
authors.affiliation: FeyeCon Development & Implementation B.V., Weesp, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Every
authors.affiliation: FeyeCon Development & Implementation B.V., Weesp, The Netherlands.
authors.forename: G W
authors.initials: GW
authors.lastname: Hofland
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, The Netherlands. Electronic address: w.jiskoot@lacdr.leidenuniv.nl.
authors.forename: W
authors.initials: W
authors.lastname: Jiskoot
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000737:chemistry*; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002645:Chickens; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D003890:Desiccation / Q000379:methods*; D006801:Humans; D009113:Muramidase / Q000032:analysis / Q000138:chemical synthesis*; D011506:Proteins / Q000032:analysis / Q000138:chemical synthesis; D012997:Solvents
chemical_list: D011506:Proteins; D012997:Solvents; D002245:Carbon Dioxide; D009113:Muramidase
keywords: Lysozyme; Protein formulation; Protein stability; Scalability; Spray drying; Supercritical carbon dioxide