Purpose

The purpose of the study was to develop a model to predict the critical quality attribute (CQA) of tablets during continuous and batch manufacturing using only critical material attributes (CMAs).

Methods

Experiments were performed using ethenzamide as the active pharmaceutical ingredient processed with batch and continuous high-shear granulators. The disintegration time of tablets was defined as the CQA, and the particle-size distribution of granules and tablet hardness were defined as the CMAs. We first investigated the influence of granulation conditions on particle-size distribution during batch and continuous granulation. We then proceeded to construct the CQA estimation model by producing tables using batch and continuous granulation.

Results

The results indicated the similarity of the granulation mechanisms, as observed by the bimodality of the distributions and the significant causal factors. Principal component analysis revealed that the CQA was influenced strongly by the particle-size distribution and that the CMA–CQA correlations were similar for both processes. Finally, a model based on partial least-squares regression could be developed that could reasonably estimate the CQA using CMAs without involving any process parameters.

Conclusion

This approach of using process-independent CQA prediction could enable flexible switching between batch and continuous manufacturing during a product life cycle, thus offering new possibilities for efficient life cycle management.

中文翻译：

---

使用优质材料属性的药片质量预测模型：批量和连续制粒之间的灵活切换

目的

该研究的目的是开发一种模型，以仅使用关键材料属性（CMA）来预测连续和批量生产过程中片剂的关键质量属性（CQA）。

方法

使用乙酰胺作为活性药物成分进行实验，并使用间歇式和连续式高剪切制粒机进行处理。将片剂的崩解时间定义为CQA，将颗粒的粒度分布和片剂硬度定义为CMA。我们首先研究了分批和连续制粒过程中制粒条件对粒度分布的影响。然后，我们通过使用分批和连续制粒制作表格来构建CQA估计模型。

结果

结果表明，通过分布的双峰性和显着的因果关系可以观察到制粒机理的相似性。主成分分析表明，CQA受粒度分布的影响很大，并且两个过程的CMA-CQA相关性相似。最后，可以建立基于偏最小二乘回归的模型，该模型可以使用CMA合理估计CQA，而无需涉及任何过程参数。

结论

这种使用与过程无关的CQA预测的方法可以在产品生命周期中实现批生产和连续制造之间的灵活切换，从而为有效的生命周期管理提供了新的可能性。