arXiv subjects

Prakitr Srisuma

Publications and source records attributed to Prakitr Srisuma.

8 recordsLinked to original sources

arXiv2026

Integrated Population Balance and Multiphysics Modeling for Predicting Undesired Agglomeration in Small Molecule Manufacturing

Agitated filter dryers (AFDs) are a crucial unit operation in small molecule manufacturing that enables simultaneous filtration, washing, and drying of active pharmaceutical ingredients. One of the key challenges in AFDs is associated with undesired agglomeration, where the presence of hard agglomerates results in off-spec products, equipment damage, and additional downstream processing. This article presents a novel mechanistic model that describes the formation of soft and hard agglomerates during agitated filter drying. By integrating population balance and multiphysics modeling, the model can accurately predict the evolution of the product temperature, moisture content, and particle size distribution, and hence quantify the extend and impact of undesired agglomeration across various operating conditions. Our proposed model-based framework enables the rational design and operation of AFDs for improving the product quality and process reliability.

cs.CE↗

arXiv2025

Highly Efficient Optimal Control for Lyophilization via Simulation of Discrete/Continuous Mixed-index Differential-algebraic Equations

This article presents a highly efficient optimal control algorithm and policies for lyophilization (also known as freeze drying). The optimal solutions and control policies are derived using an extended version of the simulation-based algorithm, which reformulates the optimal control problem as a hybrid discrete/continuous system of mixed-index differential-algebraic equations and subsequently calculates the optimal control vector via simulation of the resulting DAEs. Our algorithm and control policies are demonstrated via a number of case studies that encompass various lyophilization and optimal control strategies. All the case studies can be solved within less than a second on a normal laptop, regardless of their complexity. The method is several orders of magnitude faster than the traditional optimization-based techniques while giving similar/better accuracy. The proposed algorithm offers an efficient and reliable framework for optimal control of lyophilization, which can also be extended to other similar systems with phase transitions.

math.OC↗

arXiv2025

Probabilistically Robust Uncertainty Analysis and Optimal Control of Continuous Lyophilization via Polynomial Chaos Theory

Lyophilization, aka freeze drying, is a process commonly used to increase the stability of various drug products in biotherapeutics manufacturing, e.g., mRNA vaccines, allowing for higher storage temperature. While the current trends in the industry are moving towards continuous manufacturing, the majority of industrial lyophilization processes are still being operated in a batch mode. This article presents a framework that accounts for the probabilistic uncertainty during the primary and secondary drying steps in continuous lyophilization. The probabilistic uncertainty is incorporated into the mechanistic model via polynomial chaos theory (PCT). The resulting PCT-based model is able to accurately and efficiently quantify the effects of uncertainty on several critical process variables, including the temperature, sublimation front, and concentration of bound water. The integration of the PCT-based model into stochastic optimization and control is demonstrated. The proposed framework and case studies can be used to guide the design and control of continuous lyophilization while accounting for probabilistic uncertainty.

cs.CE↗

arXiv2024

Simulation-based Approach for Fast Optimal Control of a Stefan Problem with Application to Cell Therapy

This article describes a new, efficient way of finding control and state trajectories in optimal control problems by reformulation as a system of differential-algebraic equations (DAEs). The optimal control and state vectors can be obtained via simulation of the resulting DAE system with the selected DAE solver, eliminating the need for an optimization solver. Our simulation-based approach is demonstrated and benchmarked against various optimization-based algorithms via four case studies associated with the optimization and control of a Stefan problem for cell therapy. The simulation-based approach is faster than every optimization-based method by more than an order of magnitude while giving similar/better accuracy in all cases. The solution obtained from the simulation-based approach is guaranteed to be optimal provided that at least one constraint or algebraic equation resulting from the reformulation remains active at all times. The proposed technique offers an efficient and reliable framework for optimal control, serving as a promising alternative to the traditional techniques in applications where speed is crucial, e.g., real-time online model predictive control.

eess.SY↗

arXiv2024

Mechanistic Modeling of Continuous Lyophilization for Biopharmaceutical Manufacturing

Lyophilization (aka freeze drying) is a typical process in pharmaceutical manufacturing used for improving the stability of various drug products, including its recent applications to mRNA vaccines. While extensive efforts have been dedicated to shifting the pharmaceutical industry toward continuous manufacturing, the majority of industrial-scale lyophilization is still being operated in a batch mode. This article presents the first mechanistic model for a complete continuous lyophilization process, which comprehensively incorporates and describes key transport phenomena in all three steps of lyophilization, namely freezing, primary drying, and secondary drying. The proposed model considers the state-of-the-art lyophilization technology, in which vials are suspended and move continuously through the process. The validated model can accurately predict the evolution of critical process parameters, including the product temperature, ice/water fraction, sublimation front position, and concentration of bound water, for the entire process. Several applications related to model-based process design and optimization of continuous lyophilization are also demonstrated. The final model is made available in MATLAB and Julia as an open-source software package called ContLyo, which can ultimately be leveraged for guiding the design and development of future continuous lyophilization processes.

cs.CE↗

arXiv2024

Mechanistic Modeling and Analysis of Thermal Radiation in Conventional, Microwave-assisted, and Hybrid Freeze Drying for Biopharmaceutical Manufacturing

In freeze drying, thermal radiation has a significant effect on the drying process of vials located near the corner and edge of the trays, resulting in non-uniformity of the products. Understanding and being able to predict the impact of thermal radiation are therefore critical to accurate determination of the drying process endpoint given the variation in heat transfer of each vial. This article presents a new mechanistic model that describes complex thermal radiation during primary drying in conventional, microwave-assisted, and hybrid freeze drying. Modeling of thermal radiation employs the diffuse gray surface model and radiation network approach, which systematically and accurately incorporates simultaneous radiation exchange between every surface including the chamber wall and vials, allowing the framework to be seamlessly applied for analyzing various freeze-dryer designs. Model validation with data from the literature shows accurate prediction of the drying times for all vials, including inner, edge, and corner vials. The validated model is demonstrated for thermal radiation analysis and parametric studies to guide the design and optimization of freeze dryers.

cs.CE↗

arXiv2024

Real-time Estimation of Bound Water Concentration during Lyophilization with Temperature-based State Observers

Lyophilization (aka freeze drying) has been shown to provide long-term stability for many crucial biotherapeutics, e.g., mRNA vaccines for COVID-19, allowing for higher storage temperature. The final stage of lyophilization, namely secondary drying, entails bound water removal via desorption, in which accurate prediction of bound water concentration is vital to ensuring the quality of the lyophilized product. This article proposes a novel technique for real-time estimation of the residual moisture during secondary drying in lyophilization. A state observer is employed, which combines temperature measurement and mechanistic understanding of heat transfer and desorption kinetics, without requiring any online concentration measurement. Results from both simulations and experimental data show that the observer can accurately estimate the concentration of bound water in real time for all possible concentration levels, operating conditions, and measurement noise. This framework can also be applied for monitoring and control of the residual moisture in other desorption-related processes.

eess.SY↗

arXiv2023

Automated Translation and Accelerated Solving of Differential Equations on Multiple GPU Platforms

We demonstrate a high-performance vendor-agnostic method for massively parallel solving of ensembles of ordinary differential equations (ODEs) and stochastic differential equations (SDEs) on GPUs. The method is integrated with a widely used differential equation solver library in a high-level language (Julia's DifferentialEquations.jl) and enables GPU acceleration without requiring code changes by the user. Our approach achieves state-of-the-art performance compared to hand-optimized CUDA-C++ kernels while performing 20--100$\times$ faster than the vectorizing map (vmap) approach implemented in JAX and PyTorch. Performance evaluation on NVIDIA, AMD, Intel, and Apple GPUs demonstrates performance portability and vendor-agnosticism. We show composability with MPI to enable distributed multi-GPU workflows. The implemented solvers are fully featured -- supporting event handling, automatic differentiation, and incorporation of datasets via the GPU's texture memory -- allowing scientists to take advantage of GPU acceleration on all major current architectures without changing their model code and without loss of performance. We distribute the software as an open-source library https://github.com/SciML/DiffEqGPU.jl

cs.DC↗