Determining Maximum Sublimation Rate for a Production Lyophilizer: Computational Modeling and Comparison With Ice Slab Tests

Kshirsagar, Vaibhav; Tchessalov, Serguei; Kanka, Frank; Hiebert, David; Alexeenko, Alina

doi:10.1016/j.xphs.2018.10.061

Cited by 33 publications

(17 citation statements)

References 16 publications

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“…Minimum controllable pressure (or minimum attenable chamber pressure 35 ) is the pressure that freeze-dryer can control (or attain) at a given sublimation rate in absence of nitrogen or air injection. MCP as a function of sublimation rate (provided as an either experimentally determined curve 35 or through CFD modeling 36 ) is specific to freeze-dryer and load. Other interpretation of this term is that this curve represents maximum sublimation rate supported by freeze-dryer as a function of chamber pressure.…”

Section: Equipment Limitationsmentioning

confidence: 99%

“…2) and the MCP data fit to quadratic Equations with coefficients A, B & C. The minimum controllable pressure is the chamber pressure at a given sublimation rate determined by ice slab experiment. 36 During cycle design for a given batch size, the pressure set point must be higher than MCP for a calculated sublimation rate. The maximum sublimation rate (max SR) is determined by conducting ice slab study on the lyophilizer similarly to procedure shown in chart below (Fig.…”

Section: Equipment Limitationsmentioning

confidence: 99%

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Application of First Principles Primary Drying Model to Lyophilization Process Design and Transfer: Case Studies From the Industry

Tchessalov

Latshaw

Nulu

et al. 2021

Journal of Pharmaceutical Sciences

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Lyophilization modeling is well documented in academic circles but has not yet been widely adopted by pharmaceutical manufacturing companies. To facilitate wider adoption and implementation, an accessible ExcelTMebased tool is provided, presenting several fresh examples as a practical introduction to the process of modeling the primary drying phase. Case studies are presented of the tool's application during process development and scale up which highlight business benefits that have been realized by using the model. The authors and contributors are members of the BioPhorum's Lyophilization Workstream and represent several pharmaceutical companies. The current manuscript is intended to serve as a pathway to not only share the collective knowledge on the topic but also accelerate its adoption in the industry.

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Section: Equipment Limitationsmentioning

confidence: 99%

Section: Equipment Limitationsmentioning

confidence: 99%

Application of First Principles Primary Drying Model to Lyophilization Process Design and Transfer: Case Studies From the Industry

Tchessalov

Latshaw

Nulu

et al. 2021

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, the minimum chamber pressure is limited by the capability of the freeze-drying equipment. [31][32][33] In this sense, a PDS offers a method to identify the product and equipment limitations and to select the most optimized and robust process parameters for a given formulation.…”

Section: Cqasmentioning

confidence: 99%

An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals

Assegehegn

Fuente

Franco

et al. 2020

Journal of Pharmaceutical Sciences

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The application of quality by design (QbD) is becoming an integral part of the formulation and process development for pharmaceutical products. An essential feature of the QbD philosophy is the design space. In this sense, a new approach to construct a process design space (PDS) for the primary drying section of a freeze-drying process is addressed in this paper. An effective customized design of experiments (DoE) is developed for freeze-drying experiments. The results obtained from the DoE are then used to construct the product-based PDS. The proposed product-based PDS construction approach has several advantages, including (1) eliminating assumptions on the heat transfer coefficient and dried product resistance, as it is constructed from experimental results specifically obtained from a given formulation, yielding more realistic and reliable results and (2) PDS construction based on a narrow range of product temperatures and considering the variations in product temperature and sublimation rate of vials across a shelf. This guarantees the effectiveness and robustness of the process and facilitates the process scale-up and transfer. The PDS developed herein was experimentally verified. The PDS predicted parameters were in excellent agreement with the experimentally obtained parameters.

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“…The theoretical pressure ratio assumes a "clean" cylinder. Kshirsagar and coworkers (6) reported that the isolation valve, contained within the connecting duct in the LyoStar freeze-dryers, reduces the cross-sectional area available for flow of gasses. The resulting pressure drop causes an increase in chamber pressure and would increase the chamber-to-condenser pressure ratio.…”

Section: Minimum Controllable Pressure Methodsmentioning

confidence: 99%

Equipment Capability Measurement of Laboratory Freeze-Dryers: a Comparison of Two Methods

et al. 2021

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The objective of this investigation was to evaluate two methods for measuring the maximum sublimation rate that a freeze-dryer will support—the minimum controllable pressure method and the choke point method. Both methods gave equivalent results, but the minimum controllable pressure method is preferred, since it is easier, faster, and less subjective. The ratio of chamber pressure to condenser pressure corresponding to the onset of choked flow was considerably higher in this investigation (up to about 20:1) than in previously published reports. This ratio was not affected by the location of the pressure gauge on the condenser; that is, on the foreline of the vacuum pump versus on the body of the condenser itself. The total water loss due to sublimation as measured by tunable diode laser absorption spectroscopy was consistently within 5% of gravimetrically determined weight loss, regardless of whether the measurement took place during choked versus non-choked process conditions.

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Determining Maximum Sublimation Rate for a Production Lyophilizer: Computational Modeling and Comparison With Ice Slab Tests

Cited by 33 publications

References 16 publications

Application of First Principles Primary Drying Model to Lyophilization Process Design and Transfer: Case Studies From the Industry

Application of First Principles Primary Drying Model to Lyophilization Process Design and Transfer: Case Studies From the Industry

An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals

Equipment Capability Measurement of Laboratory Freeze-Dryers: a Comparison of Two Methods

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