Bulk Dynamic Spray Freeze-Drying Part 1: Modeling of Droplet Cooling and Phase Change

Sebastião, Israel B.; Bhatnagar, Bakul; Tchessalov, Serguei; Ohtake, Satoshi; Plitzko, Matthias; Luy, Bernhard; Alexeenko, Alina

doi:10.1016/j.xphs.2019.01.009

Cited by 34 publications

(13 citation statements)

References 39 publications

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“…Unit operations of the future that rely on different heat transfer mechanisms to reduce cycle time (microwave drying, infrared drying, vacuum drying, spray drying) (7)(8)(9)(10) or drying outside of the vial (spray drying, bulk drying, filter drying, etc.) (11)(12)(13)(14) should enable flexibility that traditional batch freeze dryers cannot provide. It should be noted that many of these alternative drying approaches are uniquely utilized in the food industry in a reliable manner for commercial production of food in a non-GMP environment.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Microwave Vacuum Drying as an Alternative to Freeze-Drying of Biologics and Vaccines: the Power of Simple Modeling to Identify a Mechanism for Faster Drying Times Achieved with Microwave

Bhambhani¹,

Stanbro²,

Roth³

et al. 2021

AAPS PharmSciTech

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Vial-based lyophilization for biopharmaceuticals has been an indispensable cornerstone process for over 50 years. However, the process is not without significant challenges. Capital costs to realize a lyophilized drug product facility, for example, are very high. Similarly, heat and mass transfer limitations inherent in lyophilization result in drying cycle on the order of several days while putting practical constraints on available formulation space, such as solute mass percentage or fill volume in a vial. Through collaboration with an external partner, we are exploring microwave vacuum drying (MVD) as a faster drying process to vial lyophilization wherein the heat transfer process occurs by microwave radiation instead of pure conduction from the vial. Drying using this radiative process demonstrates greater than 80% reduction in drying time over traditional freeze-drying times while maintaining product activity and stability. Such reduction in freeze-drying process times from days to several hours is a welcome change as it enables flexible manufacturing by being able to better react to changes either in terms of product volume for on-demand manufacturing scenarios or facilities for production (e.g., scale-out over scale-up). Additionally, by utilizing first-principle modeling coupled with experimental verification, a mechanism for faster drying times associated with MVD is proposed in this article. This research, to the best of our knowledge, forms the very first report of utilizing microwave vacuum drying for vaccines while utilizing the power of simplified models to understand drying principles associated with MVD.

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Section: Introductionmentioning

confidence: 99%

Evaluation of Microwave Vacuum Drying as an Alternative to Freeze-Drying of Biologics and Vaccines: the Power of Simple Modeling to Identify a Mechanism for Faster Drying Times Achieved with Microwave

Bhambhani¹,

Stanbro²,

Roth³

et al. 2021

AAPS PharmSciTech

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“…Solvent sublimation of atomized particles has often led to the formation of spherical, porous particles with low density, which promotes aerosolization [ 9 ]. Furthermore, recent developments in SFD technology have allowed production scale-up and continuous manufacture to become possible [ 5 , 24 ], making it a feasible method to manufacture protein therapeutics on an industrial scale. However, our understanding of SFD is still rather limited compared to other drying methods, such as SD and freeze-drying, partially due to its rather diverse approach in producing dry powder.…”

Section: Discussionmentioning

confidence: 99%

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Pan

Lam

2021

Pharmaceutics

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The prospect of inhaled biologics has garnered particular interest given the benefits of the pulmonary route of administration. Pertinent considerations in producing inhalable dry powders containing biological medicines relate to aerosol performance and protein stability. Spray-freeze-drying (SFD) has emerged as an established method to generate microparticles that can potentially be deposited in the lungs. Here, the SFD conditions and formulation composition were evaluated using bovine serum albumin (BSA) as a model protein and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) as the protein stabilizer. A factorial design analysis was performed to investigate the effects of BSA content, solute concentration of feed solution, and atomization gas flow rate on dispersibility (as an emitted fraction), respirability (as fine particle fraction), particle size, and level of protein aggregation. The atomization gas flow rate was identified as a significant factor in influencing the aerosol performance of the powder formulations and protein aggregation. Nonetheless, high atomization gas flow rate induced aggregation, highlighting the need to further optimize the formulation. Of note, all the formulations exhibited excellent dispersibility, while no fragmentation of BSA occurred, indicating the feasibility of SFD and the promise of HPβCD as an excipient.

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“…Therefore, the establishment of an appropriate freezing model is of great significance for the development, industrial design, and scale of SFD equipment. Sebastiao et al [36] established a single droplet spray freezing model to study the influence of different process parameters on the droplet freezing process and the theoretical operating limit of SFD equipment. The model described the evolution process of the position, total mass, speed, temperature, and solute concentration of the single droplet during its fall in the cooling tower.…”

Section: Freezing and Flow Of Atomized Droplets In Flow Fieldmentioning

confidence: 99%

Spray Freezing Coating on the Carrier Particles for Powder Preparation

Wang

Zhang

et al. 2022

Coatings

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Carrier particle spray freeze-drying is a new technology with high added value for thermosensitive powder spray freeze-drying. The technology includes the following steps: atomization, coating, freezing, and drying. Due to the action of carrier particles, the condensation of frozen droplets in the conventional spray freeze-drying process is overcome. However, there are many influencing factors involved in the process of freezing coating. The mechanism of the complex droplet collision freezing process still needs to be studied. In this paper, from the perspective of spray freezing coating after atomized droplets collide with low-temperature carrier particles, the coating process and freezing process of single droplets impacting the sphere are analyzed microscopically. The freezing coating processes of static and dynamic carrier particles are reviewed. Moreover, the surface evaluation of powder and equipment development for creating powder products is discussed.

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Bulk Dynamic Spray Freeze-Drying Part 1: Modeling of Droplet Cooling and Phase Change

Cited by 34 publications

References 39 publications

Evaluation of Microwave Vacuum Drying as an Alternative to Freeze-Drying of Biologics and Vaccines: the Power of Simple Modeling to Identify a Mechanism for Faster Drying Times Achieved with Microwave

Evaluation of Microwave Vacuum Drying as an Alternative to Freeze-Drying of Biologics and Vaccines: the Power of Simple Modeling to Identify a Mechanism for Faster Drying Times Achieved with Microwave

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Spray Freezing Coating on the Carrier Particles for Powder Preparation

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