The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process
The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process
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DOI：
10.3390/pharmaceutics12030279
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发表时间：
2020-03-01
期刊：
影响因子：
5.4
通讯作者：
Lakio, Satu
中科院分区：
文献类型：
--
作者：
Ervasti, Tuomas;Niinikoski, Hannes;Lakio, Satu
分离是基于批次的直接压制(BDC)工艺中的常见问题，特别是对于低剂量片剂产品，制备均质混合物也是如此。目前的工作范围是探索连续直接压缩(CDC)过程是否可以作为解决这些挑战的办法。此外，还对低剂量片剂的平台型制剂的原理进行了论证。配方中填料辅料和原料药的组合适用于直接压制，但在BDC工艺中也容易产生偏析。CDC工艺被发现是非常有前景的；结果表明，用所研究的两种原料药都可以成功地生产出具有所需质量参数的片剂。粉末分析表明，原料药在物理性质上表现出一些根本的不同，这也反映在粉末混合物的性质上，从而最终反映在加工过程中。然而，工艺参数，特别是搅拌机叶轮速度对最终产品质量没有任何显著影响。这项研究表明，疾控中心流程可以成为解决所述挑战的可行解决方案。此外，使用通用平台配方制造似乎是生产低剂量片剂的可行方法。
Segregation is a common problem in batch-based direct compression (BDC) processes, especially with low-dose tablet products, as is the preparation of a homogenous mixture. The scope of the current work was to explore if a continuous direct compression (CDC) process could serve as a solution for these challenges. Furthermore, the principle of a platform formulation was demonstrated for low dose tablets. The combination of filler excipients and the API in the formulation used was suitable for direct compression, but also prone to induce segregation in BDC process. The CDC process was found to be very promising; it was shown that tablets with the desired quality parameters could be manufactured successfully with both of the APIs studied. Powder analysis indicated that the APIs display some fundamental differences in their physical properties, which was also reflected in powder mixture properties and, hence, eventually in processing. However, process parameters, especially mixer impeller speed, were not found to have any significant influence on end product quality. The study suggests that a CDC process can be a viable solution to resolve the challenges described. Moreover, manufacturing by using a universal platform formulation seems to be a feasible way for producing low-dose tablets.