Schomberg Ann Kathrin, Kwade Arno, Finke Jan Henrik
Institute for Particle Technology, Technische Universität Braunschweig, Volkmaroder Str.5, 38104 Braunschweig, Germany.
Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Str. 35A, 38106 Braunschweig, Germany.
Pharmaceutics. 2020 Mar 10;12(3):248. doi: 10.3390/pharmaceutics12030248.
For the efficient and safe production of pharmaceutical tablets, a deep process understanding is of high importance. An essential process step during tableting is the die filling, as it is responsible for a consistent tablet weight and drug content. Furthermore, it affects the results of subsequent process steps, compaction and ejection, and thus critical quality attributes. This study focuses on understanding the influences of process parameters and material properties on die filling on a rotary tablet press. By the systematic variation in process parameters as the turret and paddle speeds as well as the fill and dosing depths, five formulations with differing properties are processed. Analysis of the normalized tablet weight, called filling yield, revealed different limitation mechanisms of the filling process, i.e., incomplete filled dies for certain parameter settings. Kinetic limitations occur due to a short residence time under the feed frame (filling time) caused by high turret speeds, which additionally induce high tablet weight variation coefficients. Characteristic maximum turret speeds at certain paddle speeds can be found to still achieve complete filling. At low turret speeds, densification of the powder inside the dies takes place, induced by two mechanisms: either high paddle speeds or high overfill ratios, or a combination of both. The challenge to fill the dies completely as well as avoid densification is dependent on material properties as the flowability. The mass discharge rate from an orifice was found to be in a linear correlation to the filling results of different formulations below complete filling.
为了高效、安全地生产药物片剂,深入了解工艺过程至关重要。压片过程中的一个关键工艺步骤是模孔填充,因为它决定了片剂重量和药物含量的一致性。此外,它还会影响后续工艺步骤(压实和脱模)的结果,进而影响关键质量属性。本研究着重于理解工艺参数和物料特性对旋转压片机模孔填充的影响。通过系统改变工艺参数,如转塔速度和桨叶速度以及填充深度和计量深度,对五种性质不同的配方进行了处理。对归一化片剂重量(即填充收率)的分析揭示了填充过程的不同限制机制,即对于某些参数设置,模孔填充不完全。由于转塔速度过高导致在进料框架下的停留时间过短(填充时间),会出现动力学限制,这还会导致片剂重量变异系数过高。在特定桨叶速度下,可以找到仍能实现完全填充的特征性最大转塔速度。在低转塔速度下,模孔内的粉末会因两种机制而发生致密化:要么是桨叶速度过高,要么是过量填充率过高,或者两者兼而有之。完全填充模孔并避免致密化的挑战取决于物料特性,如流动性。发现在完全填充以下,孔口的质量排放速率与不同配方的填充结果呈线性相关。