Optimization of the bake-on siliconization of cartridges. Part II: Investigations into burn-in time and temperature.
Combination products have become popular formats for the delivery of parenteral medications. Bake-on siliconization of glass syringes or cartridges allows good piston break-loose and gliding during injection at low silicone levels. Although widely implemented in industry, still little is known and published on the effect of the bake-on process on the silicone level, layer thickness and chemical composition. In this study, cartridges were bake-on siliconized in a heat-tunnel by varying both temperature from 200 to 350°C for 12min and time from 5min to 3h at 316°C. Furthermore, a heat-oven with air-exchange was established as an experimental model. Heat treatment led to a time- and temperature-dependent decrease in the silicone level and layer thickness. After 1h at 316°C lubrication was insufficient. The silicone levels substantially decreased between 250 and 316°C after 12min. After bake-on, the peak molecular weight of the silicone remained unchanged while fractions below 5000g/mol were removed at 316 and 350°C. Cyclic low molecular weight siloxanes below 500g/mol were volatilized under all conditions. Despite most of the baked-on silicone was solvent-extractable, contact angle analysis indicated a strong binding of a remaining, thin silicone film to the glass surface.
Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 81377 Munich, Germany.
Stefanie
S
Funke
F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
Julia
J
Matilainen
F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
Heiko
H
Nalenz
F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
Karoline
K
Bechtold-Peters
F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
Hanns-Christian
HC
Mahler
Ludwig-Maximilians-Universität München, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany.
Florian
F
Vetter
Ludwig-Maximilians-Universität München, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany.
Christoph
C
Müller
Ludwig-Maximilians-Universität München, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany.
Franz
F
Bracher
Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 81377 Munich, Germany. Electronic address: wolfgang.friess@lrz.uni-muenchen.de.
Wolfgang
W
Friess
D002850:Chromatography, Gel; D016503:Drug Delivery Systems; D008401:Gas Chromatography-Mass Spectrometry; D007263:Infusions, Parenteral; D008970:Molecular Weight; D012828:Silicones / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature; D013818:Thermogravimetry
D012828:Silicones
3D-Laser Scanning Microscopy; Bake-on siliconization; Cartridge; FTIR; Functionality; Heat-oven; Heat-tunnel; Silicone layer thickness; Silicone level; Siloxanes