School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
Int J Pharm. 2020 Jan 25;574:118882. doi: 10.1016/j.ijpharm.2019.118882. Epub 2019 Nov 28.
The aim of the current study was to characterize the robustness of an integrated continuous direct compression (CDC) line against disturbances from feeding, i.e. impulses of API and short step disturbances. These disturbances mimicked typical variations that can be encountered during long-term manufacture. The study included a primary formulation, with API of standard particle size, which was manufactured at 5 and 10 kg/h production rates, and a modified formulation, with API of large particle size, which was manufactured at 5 kg/h production rate. Overall, the CDC line smoothened all the disturbances, fulfilling the USP uniformity of dosage units (UDU) limit for single tablets. However, runs with the modified formulation failed the pharmacopoeia UDU requirements for the entire run due to high variation between tablets. The primary formulation passed the requirements in all cases. The residence time distribution (RTD) results indicated that the primary formulation allowed better smoothening ability, and an increase in production rate led to poorer smoothening due to shorter RTD. The RTDs revealed that a substantial part of back-mixing took place after the blender. Thus, the tablet press has an important role in smoothening disturbances longer than the mean residence time of the blender, which was very short.
本研究的目的是描述集成式连续直接压缩（CDC）生产线对进料干扰（即 API 脉冲和短步干扰）的稳健性。这些干扰模拟了长期生产中可能遇到的典型变化。该研究包括一个主配方，使用标准粒径的 API，以 5 和 10 kg/h 的生产速率进行生产，以及一个具有大粒径 API 的改良配方，以 5 kg/h 的生产速率进行生产。总体而言，CDC 生产线平滑了所有干扰，满足了 USP 单片剂剂量单位（UDU）均匀度的限制。然而，由于片剂之间的差异较大，具有改良配方的运行未能通过整个运行的药典 UDU 要求。主配方在所有情况下都通过了要求。停留时间分布（RTD）结果表明，主配方允许更好的平滑能力，并且由于 RTD 较短，生产速率的增加会导致平滑能力变差。RTD 表明，在混合机之后发生了大量的返混。因此，压片机在平滑比混合机平均停留时间长的干扰方面发挥着重要作用，而混合机的平均停留时间非常短。
