Novartis-MIT Center of Continuous Manufacturing, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Product & Process Engineering Department, GlaxoSmithKline, King of Prussia 19406, PA, USA.
Genentech, Inc., 1 DNA Way, South San Francisco 94080, CA, USA.
Eur J Pharm Biopharm. 2018 Jan;122:25-36. doi: 10.1016/j.ejpb.2017.10.006. Epub 2017 Oct 9.
We developed and evaluated a solvent-free injection molding (IM) coating technology that could be suitable for continuous manufacturing via incorporation with IM tableting. Coating formulations (coating polymers and plasticizers) were prepared using hot-melt extrusion and screened via stress-strain analysis employing a universal testing machine. Selected coating formulations were studied for their melt flow characteristics. Tablets were coated using a vertical injection molding unit. Process parameters like softening temperature, injection pressure, and cooling temperature played a very important role in IM coating processing. IM coating employing polyethylene oxide (PEO) based formulations required sufficient room humidity (>30% RH) to avoid immediate cracks, whereas other formulations were insensitive to the room humidity. Tested formulations based on Eudrajit E PO and Kollicoat IR had unsuitable mechanical properties. Three coating formulations based on hydroxypropyl pea starch, PEO 1,000,000 and Opadry had favorable mechanical (<700MPa Young's modulus, >35% elongation, >95×10J/m toughness) and melt flow (>0.4g/min) characteristics, that rendered acceptable IM coats. These three formulations increased the dissolution time by 10, 15 and 35min, respectively (75% drug release), compared to the uncoated tablets (15min). Coated tablets stored in several environmental conditions remained stable to cracking for the evaluated 8-week time period.
我们开发并评估了一种无溶剂注塑（IM）涂层技术，该技术可通过与 IM 压片相结合适用于连续制造。采用热熔挤出法制备了涂层配方（涂层聚合物和增塑剂），并通过万能试验机进行的应力-应变分析进行了筛选。对选定的涂层配方进行了熔融流动特性研究。采用垂直注塑单元对片剂进行包衣。在 IM 涂层加工中，软化温度、注射压力和冷却温度等工艺参数起着非常重要的作用。基于聚氧化乙烯（PEO）的配方采用 IM 涂层需要足够的房间湿度（>30%RH）以避免立即出现裂纹，而其他配方对房间湿度不敏感。基于 Eudrajit EPO 和 Kollicoat IR 的测试配方具有不合适的机械性能。基于羟丙基豌豆淀粉、PEO 1,000,000 和 Opadry 的三种涂层配方具有良好的机械性能（<700MPa 杨氏模量、>35%伸长率、>95×10J/m 韧性）和熔融流动性能（>0.4g/min），可得到可接受的 IM 涂层。与未涂层的片剂（15 分钟）相比，这三种配方分别将溶解时间延长了 10、15 和 35 分钟（75%药物释放）。在评估的 8 周时间内，储存在多种环境条件下的包衣片剂都没有出现裂纹。
