title: Optimization of the bake-on siliconization of cartridges. Part I: Optimization of the spray-on parameters.
abstract: Biopharmaceutical products are increasingly commercialized as drug/device combinations to enable self-administration. Siliconization of the inner syringe/cartridge glass barrel for adequate functionality is either performed at the supplier or drug product manufacturing site. Yet, siliconization processes are often insufficiently investigated. In this study, an optimized bake-on siliconization process for cartridges using a pilot-scale siliconization unit was developed. The following process parameters were investigated: spray quantity, nozzle position, spray pressure, time for pump dosing and the silicone emulsion concentration. A spray quantity of 4mg emulsion showed best, immediate atomization into a fine spray. 16 and 29mg of emulsion, hence 4-7-times the spray volume, first generated an emulsion jet before atomization was achieved. Poor atomization of higher quantities correlated with an increased spray loss and inhomogeneous silicone distribution, e.g., due to runlets forming build-ups at the cartridge lower edge and depositing on the star wheel. A prolonged time for pump dosing of 175ms led to a more intensive, long-lasting spray compared to 60ms as anticipated from a higher air-to-liquid ratio. A higher spray pressure of 2.5bar did not improve atomization but led to an increased spray loss. At a 20mm nozzle-to-flange distance the spray cone exactly reached the cartridge flange, which was optimal for thicker silicone layers at the flange to ease piston break-loose. Initially, 10μg silicone was sufficient for adequate extrusion in filled cartridges. However, both maximum break-loose and gliding forces in filled cartridges gradually increased from 5-8N to 21-22N upon 80weeks storage at room temperature. The increase for a 30μg silicone level from 3-6N to 10-12N was moderate. Overall, the study provides a comprehensive insight into critical process parameters during the initial spray-on process and the impact of these parameters on the characteristics of the silicone layer, also in context of long-term product storage. The presented experimental toolbox may be utilized for development or evaluation of siliconization processes.
authors.affiliation: Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 81377 München, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Funke
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Matilainen
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors.forename: Heiko
authors.initials: H
authors.lastname: Nalenz
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors.forename: Karoline
authors.initials: K
authors.lastname: Bechtold-Peters
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.affiliation: Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 81377 München, Germany. Electronic address: Wolfgang.Friess@lrz.uni-muenchen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friess
mesh_terms: D004655:Emulsions; D012828:Silicones / Q000737:chemistry*
chemical_list: D004655:Emulsions; D012828:Silicones
keywords: 3D-Laser Scanning Microscopy; Cartridge; FTIR; Functionality; Silicone distribution; Silicone layer thickness; Siliconization; Spray process