Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, 40225 Duesseldorf, Germany; Novartis AG, Novartis Campus, 4002 Basel, Switzerland.
Novartis AG, Novartis Campus, 4002 Basel, Switzerland.
Eur J Pharm Biopharm. 2018 Dec;133:224-231. doi: 10.1016/j.ejpb.2018.09.026. Epub 2018 Oct 4.
This study focussed on investigating the coupling of continuous manufacturing of drug substance and continuous manufacture of drug product. An important step in such an integrated end-to-end continuous manufacturing was envisioned by dosing the API as suspension into a twin-screw wet granulation process. To achieve this goal, a model drug substance (ibuprofen) was fed as a concentrated aqueous suspension (50% w/w) into a twin-screw granulator and compared against traditional solid feeding of the model drug substance to meet a target ibuprofen load of 60% w/w in the formulation. Granulation and compaction behaviour were evaluated to determine the impact of feeding API as suspension in twin-screw wet granulation on the critical quality attributes of the drug product. It was demonstrated that the ibuprofen suspension feed is comparable with the ibuprofen dry blend feed in twin-screw wet granulation. Next to enabling end-to-end continuous manufacturing, API suspension feed in twin-screw wet granulation could afford a number of additional advantages including manufacturing efficiency by removing the drying step for API, or overcoming processing issues linked to the bulk properties of the API powder (e.g. flowability).
本研究集中于考察原料药连续制造与药物产品连续制造的结合。在这种端到端集成的连续制造中，一个重要步骤是将 API 作为混悬液计量加入双螺杆湿法造粒工艺中。为了实现这一目标，将模型药物物质（布洛芬）作为浓水溶液（50%w/w）进料至双螺杆造粒机中，并与模型药物物质的传统固体进料进行比较，以满足制剂中 60%w/w 的目标布洛芬负载量。评估了造粒和压实行为，以确定在双螺杆湿法造粒中以混悬液形式进料 API 对药物产品关键质量属性的影响。结果表明，在双螺杆湿法造粒中，布洛芬混悬液进料与布洛芬干混进料相当。除了能够实现端到端的连续制造之外，双螺杆湿法造粒中的 API 混悬液进料还可以带来许多其他优势，包括通过去除 API 的干燥步骤来提高制造效率，或者克服与 API 粉末的堆积性质相关的加工问题（例如流动性）。
