Matić Josip, Alva Carolina, Witschnigg Andreas, Eder Simone, Reusch Kathrin, Paudel Amrit, Khinast Johannes
Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
Leistritz Pharma Extrusion, Markgrafenstraße, 29-39 1, 90459 Nürnberg, Germany.
Int J Pharm X. 2020 Nov 19;2:100062. doi: 10.1016/j.ijpx.2020.100062. eCollection 2020 Dec.
In product development, it is crucial to choose the appropriate drug manufacturing route accurately and timely and to ensure that the technique selected is suitable for achieving the desired product quality. Guided by the QbD principles, the pharmaceutical industry is currently transitioning from batch to continuous manufacturing. In this context, process understanding and prediction are becoming even more important. With regard to hot melt extrusion, the process setup, optimization and scale-up in early stages of product development are particularly challenging due to poor process understanding, complex product-process relationship and a small amount of premix available for extensive experimental studies. Hence, automated, quick and reliable process setup and scale-up requires simulation tools that are accurate enough to capture the process and determine the product-process relationships. To this end, the effect of process settings on the degradation of the active pharmaceutical ingredient (API) in a lab-scale Leistritz ZSE12 extruder was investigated. As part of the presented study, the limitations of traditional process analysis using integral process values were investigated, together with the potential that simulations may have in predicting the process performance and the product quality. The results of our investigation indicate that the average melt temperatures and the exposure times in specific zones along the screw configuration correlate well with the API degradation values and can be used as potent process design criteria to simplify the process development.
在产品开发中，准确及时地选择合适的药物制造路线并确保所选技术适合实现所需的产品质量至关重要。在质量源于设计（QbD）原则的指导下，制药行业目前正从分批生产向连续生产过渡。在此背景下，过程理解和预测变得更加重要。对于热熔挤出而言，由于对过程了解不足、产品 - 过程关系复杂以及用于广泛实验研究的预混料量少，产品开发早期阶段的工艺设置、优化和放大尤其具有挑战性。因此，自动化、快速且可靠的工艺设置和放大需要足够精确以捕捉过程并确定产品 - 过程关系的模拟工具。为此，研究了在实验室规模的莱斯特瑞兹ZSE12挤出机中工艺设置对活性药物成分（API）降解的影响。作为本研究的一部分，研究了使用积分过程值进行传统过程分析的局限性，以及模拟在预测过程性能和产品质量方面可能具有的潜力。我们的研究结果表明，沿螺杆结构特定区域的平均熔体温度和暴露时间与API降解值密切相关，可作为有效的工艺设计标准来简化工艺开发。
