当前位置：
X-MOL 学术
›
Ind. Eng. Chem. Res.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Visualizing and Understanding Batch Heterogeneity During Freeze-Drying Using Shelf-Scale Infrared Thermography
Industrial & Engineering Chemistry Research ( IF 3.8 ) Pub Date : 2024-09-13 , DOI: 10.1021/acs.iecr.4c02215 Leif-Thore Deck 1 , Nicole Ferru 1 , Andraž Košir 1 , Marco Mazzotti 1
Industrial & Engineering Chemistry Research ( IF 3.8 ) Pub Date : 2024-09-13 , DOI: 10.1021/acs.iecr.4c02215 Leif-Thore Deck 1 , Nicole Ferru 1 , Andraž Košir 1 , Marco Mazzotti 1
Affiliation
|
Various biopharmaceutical products are distributed as freeze-dried formulations in vials. Minimizing batch heterogeneity, which refers to the variability of relevant properties among vials and negatively affects product quality, represents a major challenge in process design and operation. Both the root causes of batch heterogeneity and its dependence on the operating conditions of the process remain poorly understood. To study batch heterogeneity, we here introduce a quantitative tool consisting of an infrared thermography setup (camera plus mirror) capable of monitoring non invasively and online the temperature of 60 vials densely packed on a shelf during freeze-drying. The stochastic nature of nucleation, the differences in heat transfer between vials in the core and at the edges of the batch on the shelf, and the heat transfer between neighboring vials are all demonstrated to be causes of heterogeneity during freezing. The last phenomenon causes the latent heat released by a vial upon nucleation to heat up its neighboring vials, thus delaying their nucleation. Based on the results obtained using a mechanistic model, whose predictive capabilities were confirmed by experiments, fast cooling rates and sparse vial arrangements were identified as means to mitigate batch heterogeneity. Regarding drying, the setup enabled the determination of the end point of primary drying, a process feature that is essential for whole-process optimization.
中文翻译：
使用货架级红外热成像可视化和了解冻干过程中的批次异质性
各种生物制药产品以冻干制剂形式装在小瓶中进行销售。最大限度地减少批次异质性（指的是小瓶之间相关特性的变异性并对产品质量产生负面影响）是工艺设计和操作中的一项重大挑战。批次异质性的根本原因及其对工艺操作条件的依赖性仍然知之甚少。为了研究批次异质性，我们在此引入一种定量工具，由红外热成像装置（相机加镜子）组成，能够非侵入性地在线监测冷冻干燥过程中密集包装在架子上的 60 个小瓶的温度。成核的随机性、中心小瓶和货架上批次边缘之间的传热差异以及相邻小瓶之间的传热均被证明是冷冻过程中不均匀性的原因。最后一种现象导致小瓶在成核时释放的潜热加热其邻近的小瓶，从而延迟它们的成核。根据使用机械模型获得的结果（其预测能力已通过实验得到证实），快速冷却速率和稀疏的小瓶排列被确定为减轻批次异质性的方法。在干燥方面，该设置能够确定初级干燥的终点，这是对整个过程优化至关重要的过程特征。
更新日期：2024-09-13
中文翻译：
使用货架级红外热成像可视化和了解冻干过程中的批次异质性
各种生物制药产品以冻干制剂形式装在小瓶中进行销售。最大限度地减少批次异质性（指的是小瓶之间相关特性的变异性并对产品质量产生负面影响）是工艺设计和操作中的一项重大挑战。批次异质性的根本原因及其对工艺操作条件的依赖性仍然知之甚少。为了研究批次异质性，我们在此引入一种定量工具，由红外热成像装置（相机加镜子）组成，能够非侵入性地在线监测冷冻干燥过程中密集包装在架子上的 60 个小瓶的温度。成核的随机性、中心小瓶和货架上批次边缘之间的传热差异以及相邻小瓶之间的传热均被证明是冷冻过程中不均匀性的原因。最后一种现象导致小瓶在成核时释放的潜热加热其邻近的小瓶，从而延迟它们的成核。根据使用机械模型获得的结果（其预测能力已通过实验得到证实），快速冷却速率和稀疏的小瓶排列被确定为减轻批次异质性的方法。在干燥方面，该设置能够确定初级干燥的终点，这是对整个过程优化至关重要的过程特征。
京公网安备 11010802027423号