Bulk Dynamic Spray Freeze-Drying Part 2: Model-Based Parametric Study for Spray-Freezing Process Characterization

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

doi:10.1016/j.xphs.2019.01.011

Cited by 23 publications

(8 citation statements)

References 20 publications

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“…As the crystal growth velocity is dependent on the transfer of heat away from the freezing front, the cooling rate and viscosity are critical in controlling the freezing front velocity. We approximate the ratio between convective and conductive heat fluxes (Biot number) on the droplets regardless of morphology to be similar to pure water droplets with thermal conductivity h c ≅ 1, thermal transfer coefficient k c ≅ 1000, and diameter D and find Bi = ( h c / k c )( D /6) ≪ 1, which points to a uniform temperature profile inside the droplets . Dextran concentration and molecular weight thereby affect the heat and mass transfer processes that influence the ice growth velocity.…”

Section: Results and Discussionmentioning

confidence: 90%

“…We approximate the ratio between convective and conductive heat fluxes (Biot number) on the droplets regardless of morphology to be similar to pure water droplets with thermal conductivity h c ≅ 1, thermal transfer coefficient k c ≅ 1000, and diameter D and find Bi = (h c /k c )(D/6) ≪ 1, which points to a uniform temperature profile inside the droplets. 64 Dextran concentration and molecular weight thereby affect the heat and mass transfer processes that influence the ice growth velocity. The constancy of lamellar spacing with varying molecular weight suggests that although the viscosity of dextran solutions increases with concentration (see Figure S4 in the SI), viscosity is not the determining factor in freezing front velocity.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Modulating the Pore Architecture of Ice-Templated Dextran Microparticles Using Molecular Weight and Concentration

et al. 2022

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Spray freeze drying (SFD) is an ice templating method used to produce highly porous particles with complex pore architectures governed by ice nucleation and growth. SFD particles have been advanced as drug carrier systems, but the quantitative description of the morphology formation in the SFD process is still challenging. Here, the pore space dimensions of SFD particles prepared from aqueous dextran solutions of varying molecular weights (40–200 kDa) and concentrations (5–20%) are analyzed using scanning electron microscopy. Coexisting morphologies composed of cellular and dendritic motifs are obtained, which are attributed to variations in the ice growth mechanism determined by the SFD system and modulation of these mechanisms by given precursor solution properties leading to changes in their pore dimensions. Particles with low-aspect ratio cellular pores showing variation of around 0.5–1 μm in diameter with precursor composition but roughly constant with particle diameter are ascribed to a rapid growth regime with high nucleation site density. Image analysis suggests that the pore volume decreases with dextran solid content. Dendritic pores (≈2−20 μm in diameter) with often a central cellular region are identified with surface nucleation and growth followed by a slower growth regime, leading to the overall dendrite surface area scaling approximately linearly with the particle diameter. The dendrite lamellar spacing depends on the concentration according to an inverse power law but is not significantly influenced by molecular weight. Particles with highly elongated cellular pores without lamellar formation show intermediate pore dimensions between the above two limiting morphological types. Analysis of variance and post hoc tests indicate that dextran concentration is the most significant factor in affecting the pore dimensions. The SFD dextran particles herein described could find use in pulmonary drug delivery due to their high porosity and biocompatibility of the matrix material.

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Section: Results and Discussionmentioning

confidence: 90%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Modulating the Pore Architecture of Ice-Templated Dextran Microparticles Using Molecular Weight and Concentration

et al. 2022

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“…This SFD technology has been used to produce high activity probiotics, coffee powder with volatile compounds, high-quality milk powder, and other powdered foods. Future research tends to focus on the development and simulation of new spray freeze-drying devices [35,47], the optimization of process parameters, the online measurement of temperature and humidity distribution, and the control of multi-level continuous drying in order to realize its compact, automatic, and energy-saving properties [48]. In recent years, new spray freeze-drying devices and methods have also been reported.…”

Section: Integrated Spray Freeze Coating Equipment and Its Engineerin...mentioning

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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“…This situation allows for accomplishing nucleation and freezing of the droplets in a span of milliseconds or seconds [58]. Rapid freezing prevents the damaging effects of phase separation on biomolecular structure by preventing, or at least minimizing, crystallization of excipients and also minimizing solutes partitioning and pH change [73][74][75]. Figure 1 depicts possible methods for performing the spray freezing step.…”

Section: Spray Freezing Techniquesmentioning

confidence: 99%

Spray Freeze-Drying as a Solution to Continuous Manufacturing of Pharmaceutical Products in Bulk

et al. 2020

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Pharmaceutical manufacturing is evolving from traditional batch processes to continuous ones. The new global competition focused on throughput and quality of drug products is certainly the driving force behind this transition which, thus, represents the new challenge of pharmaceutical manufacturing and hence of lyophilization as a downstream operation. In this direction, the present review deals with the most recent technologies, based on spray freeze-drying, that can achieve this objective. It provides a comprehensive overview of the physics behind this process and of the most recent equipment design.

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Bulk Dynamic Spray Freeze-Drying Part 2: Model-Based Parametric Study for Spray-Freezing Process Characterization

Cited by 23 publications

References 20 publications

Modulating the Pore Architecture of Ice-Templated Dextran Microparticles Using Molecular Weight and Concentration

Modulating the Pore Architecture of Ice-Templated Dextran Microparticles Using Molecular Weight and Concentration

Spray Freezing Coating on the Carrier Particles for Powder Preparation

Spray Freeze-Drying as a Solution to Continuous Manufacturing of Pharmaceutical Products in Bulk

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