Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 81377 Munich, Germany.
F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
Eur J Pharm Biopharm. 2016 Aug;105:209-22. doi: 10.1016/j.ejpb.2016.05.015. Epub 2016 Jun 17.
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.
组合产品已成为注射用药物的一种流行剂型。在玻璃注射器或小瓶上进行烤硅化处理可以在低硅水平下实现活塞的良好脱离和滑动。尽管这种烤硅化工艺在工业中得到了广泛应用，但对于其对硅含量、层厚和化学成分的影响，人们知之甚少，相关研究也很少发表。在这项研究中，通过在热隧道中以 200 至 350°C 的温度处理 12 分钟，并在 316°C 下以 5 分钟至 3 小时的时间处理，对小瓶进行了烤硅化处理。此外，还建立了一个具有空气交换的热烤箱作为实验模型。热处理会导致硅含量和层厚随时间和温度的降低而降低。在 316°C 下处理 1 小时后，润滑效果不足。在 12 分钟内，硅含量在 250 至 316°C 之间显著降低。烤硅化后，硅酮的峰值分子量保持不变，而在 316°C 和 350°C 时，分子量低于 5000g/mol 的部分被去除。所有条件下，分子量低于 500g/mol 的环状低分子量硅氧烷都会挥发。尽管大部分烤硅化的硅酮都可以用溶剂萃取，但接触角分析表明，剩余的薄硅酮膜与玻璃表面结合紧密。
