The standard operation of a batch freeze-dryer is protocol driven. All freeze-drying phases (i.e., freezing, primary and secondary drying) are programmed sequentially at fixed time points and within each phase critical process parameters (CPPs) are typically kept constant or linearly interpolated between two setpoints. This way of operating batch freeze-dryers is shown to be time consuming and inefficient. A model-based optimisation and real-time control strategy that includes model output uncertainty could help in accelerating the primary drying phase while controlling the risk of failure of the critical quality attributes (CQAs). In each iteration of the real-time control strategy, a design space is computed to select an optimal set of CPPs. The aim of the control strategy is to avoid product structure loss, which occurs when the sublimation interface temperature ( T i ) exceeds the the collapse temperature ( T c ) common during unexpected disturbances, while preventing the choked flow conditions leading to a loss of pressure control. The proposed methodology was experimentally verified when the chamber pressure and shelf fluid system were intentionally subjected to moderate process disturbances. Moreover, the end of the primary drying phase was predicted using both uncertainty analysis and a comparative pressure measurement technique. Both the prediction of T i and end of primary drying were in agreement with the experimental data. Hence, it was confirmed that the proposed real-time control strategy is capable of mitigating the effect of moderate disturbances during batch freeze-drying.

译文

批量冷冻干燥机的标准操作是协议驱动的。所有冷冻干燥阶段 (即冷冻、初级和次级干燥) 在固定的时间点被顺序地编程,并且在每个阶段内关键过程参数 (cpp) 通常保持恒定或在两个设定点之间线性内插。这种分批冷冻干燥机的操作方式显示出耗时且效率低下。包含模型输出不确定性的基于模型的优化和实时控制策略可以帮助加速主要干燥阶段,同时控制关键质量属性 (CQAs) 失效的风险。在实时控制策略的每次迭代中,都会计算一个设计空间以选择一组最佳的cpp。控制策略的目的是避免产品结构损失,当升华界面温度 (T i) 超过意外干扰期间常见的塌陷温度 (T c) 时发生损失,同时防止阻塞的流动条件导致压力损失控制。当有意使腔室压力和架子流体系统受到中等过程干扰时,对所提出的方法进行了实验验证。此外,使用不确定性分析和比较压力测量技术预测了主要干燥阶段的结束。T i和初级干燥结束的预测均与实验数据一致。因此,已经证实,所提出的实时控制策略能够减轻批量冷冻干燥过程中中等干扰的影响。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录