Ervasti Tuomas, Niinikoski Hannes, Mäki-Lohiluoma Eero, Leppinen Heidi, Ketolainen Jarkko, Korhonen Ossi, Lakio Satu
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70210 Kuopio, Finland.
Orion Pharma Oyj, 02200 Espoo, Finland.
Pharmaceutics. 2020 Mar 20;12(3):279. doi: 10.3390/pharmaceutics12030279.
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.
在基于批次的直接压片（BDC）工艺中，尤其是对于低剂量片剂产品，混合不均是一个常见问题，制备均匀混合物也是如此。当前工作的范围是探索连续直接压片（CDC）工艺是否可以作为应对这些挑战的解决方案。此外，还展示了低剂量片剂的平台配方原理。所用配方中填充剂辅料与活性药物成分（API）的组合适用于直接压片，但在BDC工艺中也容易导致混合不均。结果发现CDC工艺非常有前景；结果表明，使用所研究的两种API都能成功制造出具有所需质量参数的片剂。粉末分析表明，两种API在物理性质上存在一些根本差异，这也反映在粉末混合物性质上，并最终反映在加工过程中。然而，未发现工艺参数，尤其是混合器叶轮速度对最终产品质量有任何显著影响。该研究表明，CDC工艺可能是解决上述挑战的可行方案。此外，使用通用平台配方进行生产似乎是生产低剂量片剂的可行方法。
