开发一种高保真度数字双胞胎,使用离散元件方法进行连续的直接压缩过程. 第二部分. 校准工作流程的验证
Dalibor Jajcevic1, Johan Remmelgas1, Peter Toson1
1Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
International journal of pharmaceutics
|October 5, 2024
概括
本研究应用离散元件方法 (DEM) 模拟和减少顺序建模来预测粉末混合器性能. 校准的DEM模型准确预测药物物质度变化,减少实验需求并帮助控制策略的开发.
科学领域:
- 化学工程是化学工程的重要组成部分.
- 制药制造业 制药制造业 制药制造业
- 计算建模 计算建模
背景情况:
- 在制药制造中,持续混合粉末至关重要.
- 预测输入度变化对输出度的影响对于工艺控制至关重要.
- 之前的工作使用DEM和小规模测试建立了可靠的居住时间分布 (RTD) 模型.
研究的目的:
- 为了评估一个减少的订单模型的预测能力,连续粉末混合器在一个扩展的设计空间.
- 展示校准的离散元件方法 (DEM) 模型的应用,用于预测工艺对输入度变化的反应.
- 开发一款用于粉末混合过程中控制策略评估的计算工具.
主要方法:
- 使用校准的离散元件方法 (DEM) 工作流程进行模拟.
- 使用继电赛方法推断DEM模拟.
- 用n-CSTR模型对累积RTD曲线进行参数化,以开发减少顺序模型.
- 通过实验和模拟API度的阶段变化来验证预测.
主要成果:
- 校准的DEM模型准确地预测了连续粉末混合机对API入口度逐步变化的反应.
- 该n-CSTR模型有效参数化了预测的RTD曲线.
- 减少顺序模型能够在几秒钟内进行过程模拟,大大减少了计算工作量.
- 接力赛方法在推断DEM模拟结果方面被证明是有效的.
结论:
- 校准的DEM模型是指导和最小化粉末混合器开发中的实验工作的强大工具.
- 开发的方法有助于建立持续粉末制造的适当控制策略.
- 高准确度的DEM模拟,结合材料节约性表征,为控制策略评估提供了一个强大的平台.
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