Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Int J Pharm. 2020 Mar 15;577:119068. doi: 10.1016/j.ijpharm.2020.119068. Epub 2020 Jan 22.
Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous research identified lactose/MCC/HPMC as a robust platform formulation for several model formulations, although granulation of the high-dosed, poorly soluble API mebendazole proved challenging. Therefore, current research evaluated the binder addition method (wet or dry) as well as surfactant (SLS) addition when using PVP, instead of HPMC. Compared to the previous formulation, using HPMC as binder, all four formulations with PVP yielded significantly stronger granules at similar to significantly lower liquid to solid (L/S) ratios. Through the combination of four replicate center composite circumscribed designs, each evaluating the impact of screw speed and L/S ratio on granule quality attributes, the effect of the formulation variables was assessed. Overall, L/S ratio had the most significant impact on granule characteristics whereas the effect of screw speed was negligible. Similar granule quality attributes were obtained for each formulation, although the addition of SLS and wet binder addition significantly reduced the required L/S ratio to achieve the desired characteristics. This significant reduction could prove useful for processing other formulations requiring high amounts of moisture, which could otherwise not be dried at a high throughput due to the limited drying capacity of the dryer unit of the Consigma system.
尽管最近有几种通过连续制造技术生产的药物产品已经商业化，但对于这些技术的配方方面的知识，例如双螺杆湿法造粒，仍然相当有限。尽管高剂量、难溶性 API 甲苯咪唑的造粒具有挑战性，但之前的研究已经确定乳糖/MCC/HPMC 是几种模型配方的稳健平台配方。因此，目前的研究评估了在使用 PVP 时，将粘合剂（湿或干）以及表面活性剂（SLS）添加到配方中的方法，而不是 HPMC。与之前使用 HPMC 作为粘合剂的配方相比，使用 PVP 的所有四个配方在相似或明显更低的液固比 (L/S) 下都产生了明显更强的颗粒。通过四个重复中心复合限定设计的组合，每个设计都评估了螺杆速度和 L/S 比对颗粒质量属性的影响，评估了配方变量的影响。总体而言，L/S 比对颗粒特性的影响最大，而螺杆速度的影响可以忽略不计。尽管添加 SLS 和湿粘合剂显著降低了实现所需特性所需的 L/S 比，但每种配方都获得了相似的颗粒质量属性。这种显著的降低对于处理需要大量水分的其他配方可能非常有用，否则由于 Consigma 系统的干燥器单元的干燥能力有限，这些配方可能无法以高产量干燥。
