实施机械建模和全球灵敏度分析 (GSA) 来设计,优化和扩大滚筒压缩工艺的规模
Parind M Desai1, Chandan Bhugra1, Ananya Chowdhury2
1Drug Product Development, GSK R&D, Collegeville, PA, United States.
International journal of pharmaceutics
|May 5, 2024
概括
使用约翰逊模型的机械建模优化了高药载荷配方的滚筒紧缩. 这种方法成功地预测了固体分数,提高了过程稳定性和制药开发的扩展.
科学领域:
- 制药工程 制药工程
- 过程化学 过程化学
- 材料科学 材料科学 材料科学
背景情况:
- 制药行业越来越多地采用机械建模来提高过程稳定性,促进扩展,加快上市时间.
- 虽然已经建立了用于滚筒紧缩的建模方法,但它们对高药量配方的应用仍然有限.
研究的目的:
- 使用约翰逊机械模型,优化滚筒压缩加工,并指导使用高药载荷配方的扩展.
- 评估过程参数对固体分量 (SF) 的影响,并将模型预测与替代吞吐量方法进行比较.
主要方法:
- 约翰逊模型使用试点规模数据 (Minipactor) 进行校准,并在商业规模批量 (Macropactor) 上验证.
- 进行了全球灵敏度分析 (GSA),以评估滚动力,间隙和速度对固体分量的影响.
- 研究了吞吐量方法作为估计SF的替代方法.
主要成果:
- 约翰逊模型准确地预测了所有14个商业规模批次的固体分数值,在±0.04 SF以内.
- 吞吐量方法在11个批中的7个批中实现了±0.06 SF内的预测.
- 全球灵敏度分析确定滚动力是影响固体分量的最重要的参数.
结论:
- 机械建模,特别是约翰逊模型,为优化和扩大高药量产品的滚筒紧缩提供了强大的框架.
- 这项研究证明了机械建模的成功应用,以在制药过程中建立质量,扩大其在药物产品开发中的实用性.
- 约翰逊模型在预测固体分数方面提供了卓越的准确性,与高药载荷滚筒紧缩的吞吐量方法相比.
更多相关视频
相关概念视频
01:17Rolling Resistance: Problem Solving
323
Rolling resistance, also known as rolling friction, is the force that resists the motion of a rolling object, such as a wheel, tire, or ball, when it moves over a surface. It is caused by the deformation of the object and the surface in contact with each other, as well as other factors like internal friction, hysteresis, and energy losses within the materials. Rolling resistance opposes the object's motion, requiring additional energy to overcome it and maintain movement. In practical...
323
01:16Response Surface Methodology
127
Response Surface Methodology (RSM) is a collection of statistical and mathematical techniques used to develop, improve, and optimize processes. It is particularly valuable when many input variables or factors potentially influence a response variable.
The process of RSM involves several key steps:
The process of RSM involves several key steps:
127
01:29Mechanistic Models: Compartment Models in Algorithms for Numerical Problem Solving
52
Mechanistic models play a crucial role in algorithms for numerical problem-solving, particularly in nonlinear mixed effects modeling (NMEM). These models aim to minimize specific objective functions by evaluating various parameter estimates, leading to the development of systematic algorithms. In some cases, linearization techniques approximate the model using linear equations.
In individual population analyses, different algorithms are employed, such as Cauchy's method, which uses a...
In individual population analyses, different algorithms are employed, such as Cauchy's method, which uses a...
52
01:21Design Example: Creating a Hydraulic Model of a Dam Spillway
160
Scaled hydraulic models of dam spillways provide a practical way to replicate and study the intricate flow dynamics of these structures. Often built to a 1:15 ratio, these models allow for observing critical water behavior, such as velocity distribution, flow patterns, and energy dissipation.
160
01:30Typical Model Studies
356
Fluid mechanics model studies often utilize scaled-down systems to predict fluid behavior in full-scale environments, such as river flows, dam spillways, and structures interacting with open surfaces. Maintaining Froude number similarity in river models is crucial, as it replicates surface flow features like wave patterns and velocities.
356
01:24Bearings: Problem Solving
282
Understanding the calculations and concepts related to double-collar bearings is essential for engineers and designers to optimize the performance of these components in various applications. By analyzing the bearing under different conditions, one can ensure that it can withstand the forces and moments experienced during operation. This knowledge enables better decision-making when designing and selecting bearings for specific purposes and configurations. Consider a double-collar bearing with...
282