Surrogate modeling of dissolution behavior toward efficient design of tablet manufacturing processes
Surrogate modeling of dissolution behavior toward efficient design of tablet manufacturing processes
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溶出行为的替代模型，以实现片剂制造工艺的高效设计
DOI：
10.1016/j.compchemeng.2023.108141
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发表时间：
2023
影响因子：
4.3
通讯作者：
Hirokazu Sugiyama
中科院分区：
文献类型：
--
作者：
Kensaku Matsunami;Tomohiro Miura;Keita Yaginuma;Shuichi Tanabe;Sara Badr;Hirokazu Sugiyama
本文提出了溶出度行为的替代模型，以确定片剂生产过程中的关键输入参数。溶出行为是一种关键的质量属性，其定义为片剂中溶出的活性药物成分在溶剂中的分数的时间分布。首先使用gPROMS®通过力学模型计算了溶解行为，并用威布尔模型进行了拟合。随机森林回归从输入的模型参数中计算出威布尔模型参数。所开发的模型能够在不损失精度的情况下降低计算成本。对使用扑热息痛的干法和湿法造粒工艺进行了案例研究。结果确定了对溶解行为的关键输入和中间参数，例如颗粒体积密度和孔隙率。此外，湿法制粒比干法制粒有更快溶解的趋势。该方法有助于在有限的制药过程开发时间内提高仿真能力。
This paper presents surrogate models of dissolution behavior to identify the critical input parameters in tablet manufacturing processes. Dissolution behavior is a critical quality attribute, and is defined as the time profile of fraction of dissolved active pharmaceutical ingredients in a solvent from a tablet. Dissolution behavior was first calculated by mechanistic models using gPROMS® and fitted by the Weibull model. Random forest regression calculated the Weibull model parameters from the input model parameters. The developed models enabled to reduce computational cost without losing accuracy. Case studies were performed for both dry and wet granulation processes using paracetamol. The results identified key input and intermediate parameters to the dissolution behavior, e.g., granule bulk density and porosity. In addition, wet granulation had a tendency to make dissolution faster than dry granulation. The proposed approach can contribute to enhance simulation capabilities in the limited time of pharmaceutical process development.