The Nonsteady State Modeling of Freeze Drying: In-Process Product Temperature and Moisture Content Mapping and Pharmaceutical Product Quality Applications

Pikal, Michael J.; Cardon, Stéphane; Bhugra, Chandan; Jameel, Feroz; Rambhatla, Shailaja; Mascarenhas, W.J.; Akay, H. U.

doi:10.1081/pdt-35869

Cited by 72 publications

(56 citation statements)

References 9 publications

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“…Then Technalysis (Indianapolis, IN, USA) developed a finite element method based GUI software based on the algorithm described by Pikal. Details such as governing equations, boundary conditions, assumptions, and validations are described elsewhere [15,20]. In summary, the software uses an arbitrary LagrangianEulerian method to accurately model the sublimation front of the freeze-drying process in two-dimensional axisymmetric space.…”

Section: Finite Element Method-based Model Descriptionmentioning

confidence: 99%

“…PASSAGE is a semi-empirical numerical algorithm originally described by Pikal [15]. Then Technalysis (Indianapolis, IN, USA) developed a finite element method based GUI software based on the algorithm described by Pikal.…”

Section: Finite Element Method-based Model Descriptionmentioning

confidence: 99%

“…The steady state assumption of this model, however, fails in several respects. While the majority of primary drying is a steady state process, the period immediately following a change in shelf temperature (such as the beginning of primary drying) is in a non-steady state [15,16] and therefore this model does not apply for the entire primary drying phase. Pikal [16] states that the system does not reach steady state until 30 min after a change in shelf temperature.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the steady state model will not yield information on the residual moisture content in the dry layer [15]. PASSAGE, a commercial software package from Technalysis (Indianapolis, IN, USA), has been used to more accurately model the freezedrying process [4,15,17]. PASSAGE uses a finite element method (FEM) to solve coupled heat and mass transfer equations in a two-dimensional axisymmetric space [17].…”

Section: Introductionmentioning

confidence: 99%

“…Pikal [16] states that the system does not reach steady state until 30 min after a change in shelf temperature. Furthermore, the steady state model will not yield information on the residual moisture content in the dry layer [15]. PASSAGE, a commercial software package from Technalysis (Indianapolis, IN, USA), has been used to more accurately model the freezedrying process [4,15,17].…”

Section: Introductionmentioning

confidence: 99%

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Finite Element Method (FEM) Modeling of Freeze-drying: Monitoring Pharmaceutical Product Robustness During Lyophilization

et al. 2015

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Abstract. Lyophilization is an approach commonly undertaken to formulate drugs that are unstable to be commercialized as ready to use (RTU) solutions. One of the important aspects of commercializing a lyophilized product is to transfer the process parameters that are developed in lab scale lyophilizer to commercial scale without a loss in product quality. This process is often accomplished by costly engineering runs or through an iterative process at the commercial scale. Here, we are highlighting a combination of computational and experimental approach to predict commercial process parameters for the primary drying phase of lyophilization. Heat and mass transfer coefficients are determined experimentally either by manometric temperature measurement (MTM) or sublimation tests and used as inputs for the finite element model (FEM)-based software called PASSAGE, which computes various primary drying parameters such as primary drying time and product temperature. The heat and mass transfer coefficients will vary at different lyophilization scales; hence, we present an approach to use appropriate factors while scaling-up from lab scale to commercial scale. As a result, one can predict commercial scale primary drying time based on these parameters. Additionally, the model-based approach presented in this study provides a process to monitor pharmaceutical product robustness and accidental process deviations during Lyophilization to support commercial supply chain continuity. The approach presented here provides a robust lyophilization scale-up strategy; and because of the simple and minimalistic approach, it will also be less capital intensive path with minimal use of expensive drug substance/active material.

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Section: Finite Element Method-based Model Descriptionmentioning

confidence: 99%

Section: Finite Element Method-based Model Descriptionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Finite Element Method (FEM) Modeling of Freeze-drying: Monitoring Pharmaceutical Product Robustness During Lyophilization

et al. 2015

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Freeze‐Drying, Pharmaceuticals

Liu

2010

Encyclopedia of Industrial Biotechnology

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This article provides an overview of the fundamental aspects for pharmaceutical freeze‐drying, including the rationale for freeze‐drying process design and control, the basics of formulation development for freeze‐drying, the importance of the container‐closure system, and a general description of pharmaceutical freeze‐dryers. In the second part of this article, the challenges in freeze‐drying scale‐up and transfer, freezing control, use of cosolvent, freeze‐drying in syringes, process analytical technology, and quality‐by‐design in freeze‐drying have been discussed, and some new advancements related to these aspects are also highlighted.

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Considerations for Successful Lyophilization Process Scale‐Up, Technology Transfer, and Routine Production

Sane¹,

Hsu²

2010

Formulation and Process Development Strategies for Manufacturing Biopharmaceuticals

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The Nonsteady State Modeling of Freeze Drying: In-Process Product Temperature and Moisture Content Mapping and Pharmaceutical Product Quality Applications

Abstract: The theoretical results of in-process product temperature, primary drying time, and moisture content mapping and history are consistent with the experimental results, suggesting the theoretical model should be useful in process development and "trouble-shooting" applications.

Cited by 72 publications

References 9 publications

Finite Element Method (FEM) Modeling of Freeze-drying: Monitoring Pharmaceutical Product Robustness During Lyophilization

Finite Element Method (FEM) Modeling of Freeze-drying: Monitoring Pharmaceutical Product Robustness During Lyophilization

Freeze‐Drying, Pharmaceuticals

Considerations for Successful Lyophilization Process Scale‐Up, Technology Transfer, and Routine Production

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