Research

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14 pages, 3718 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Influence of Freezing Parameters on the Formation of Internal Porous Structure and Its Impact on Freeze-Drying Kinetics

by Patrick Levin, Vincent Meunier, Ulrich Kessler and Stefan Heinrich

Processes 2021, 9(8), 1273; https://0-doi-org.brum.beds.ac.uk/10.3390/pr9081273 - 23 Jul 2021

Cited by 6 | Viewed by 2664

The main objective of this study was firstly to investigate the influence of freezing process parameters on the formation of the internal structure of frozen coffee granules. It was investigated how these frozen internal structures affect the drying kinetics during freeze-drying. A design [...] Read more.

The main objective of this study was firstly to investigate the influence of freezing process parameters on the formation of the internal structure of frozen coffee granules. It was investigated how these frozen internal structures affect the drying kinetics during freeze-drying. A design of experiment study was carried out using the response surface method to quantify the influence of the freezing step that occurs in a scraped surface heat exchanger (SSHE). Therefore, the coffee extract at a concentration of 30% w/w is entering the SSHE as a liquid and gets partially crystallized up to a weight-based ice content of 0.364. During this step, the influence of factors like cooling temperature, scraper rotation speed and temperature cycles on ice crystal structure was investigated. In a second freezing step, the influence of freezing rates during hardening of the product by air-blast freezing is investigated, where the freezing rate is significantly affected by the cake thickness. The produced frozen granules were freeze-dried in single layer experiments. During drying the influence of internal structure on the drying kinetics was investigated. Results show that all factors have a significant impact on structure parameters for 30% w/w coffee solutions. A lower degree of supercooling during freezing in an SSHE, a higher number of temperature cycles (2 to 8 times) and lower freezing rates during hardening (2 °C/min to 10 °C/min) were leading to increased crystal size. This increase accelerates the primary drying rate and decreases the total drying time. A higher number of temperature cycles leads to a significant increase of crystal size and therefore larger pore size at the end of the primary drying. Furthermore, in combination with temperature cycles in the SSHE, it was found that high freezing rates during air blast freezing generally lead to a second nucleation step of ice crystals. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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14 pages, 2812 KiB

Open AccessFeature PaperArticle

Freeze-Drying versus Heat-Drying: Effect on Protein-Based Superabsorbent Material

by Estefanía Álvarez-Castillo, Carlos Bengoechea, Manuel Felix and Antonio Guerrero

Processes 2021, 9(6), 1076; https://0-doi-org.brum.beds.ac.uk/10.3390/pr9061076 - 21 Jun 2021

Cited by 3 | Viewed by 2141

Abstract

Porcine plasma protein is a by-product of the meat industry, which has already been applied in the manufacture of superabsorbent materials. The effects of plasticizer content (0%, 25%, 50%), together with those of the drying method (freeze-drying, thermal drying at 50 °C), during [...] Read more.

Porcine plasma protein is a by-product of the meat industry, which has already been applied in the manufacture of superabsorbent materials. The effects of plasticizer content (0%, 25%, 50%), together with those of the drying method (freeze-drying, thermal drying at 50 °C), during the processing of superabsorbent porcine plasma matrices were studied in this manuscript. Although the presence of glycerol accelerated the water absorption kinetics, the highest water absorption (~550%) was achieved by samples not containing any plasticizer. Viscoelasticity decreased at higher glycerol contents and especially after water absorption. When swollen samples were dried through freeze-drying, porous structures with a sponge-like appearance were obtained. Oppositely, thermally dried samples suffered an evident shrinkage that reduced porosity, displaying a more uniform surface. The effect of the drying method was observed since only freeze-dried samples can be rehydrated, displaying a superabsorbent ability (absorption higher than 1000%), which could be used in several applications (food, agriculture, personal care). Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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13 pages, 2570 KiB

Open AccessFeature PaperArticle

Water Vapor Pathways during Freeze-Drying of Foamed Product Matrices Stabilized by Maltodextrin at Different Concentrations

by Peter Kubbutat, Annika Tauchnitz and Ulrich Kulozik

Processes 2020, 8(11), 1463; https://0-doi-org.brum.beds.ac.uk/10.3390/pr8111463 - 15 Nov 2020

Cited by 3 | Viewed by 2640

Abstract

This study aimed to identify the water-vapor transport mechanisms through an aerated matrix during microwave freeze-drying. Due to the larger surface area and lower water vapor transport resistance of an aerated product compared to the solution, foam structures dry faster. Different foam structures [...] Read more.

This study aimed to identify the water-vapor transport mechanisms through an aerated matrix during microwave freeze-drying. Due to the larger surface area and lower water vapor transport resistance of an aerated product compared to the solution, foam structures dry faster. Different foam structures were produced with different maltodextrin (MD) concentrations (10–40%) as a foam-stabilizing agent. Depending on the initial viscosity of the solution prior to foaming, the samples differed in overrun (41–1671%) and pore size (d₅₀ = 58–553 µm). Experiments were partially performed in a freeze-drying chamber of a light microscope to visualize structural changes in-situ. Different mechanisms were identified explaining the accelerated drying of foams, depending on the MD concentration, above or below 30%. At lower MD concentration, high overruns could be produced prior to freezing with big bubbles and thin lamellae with short diffusion pathway length. At 40% MD concentration, the viscosity was too high to integrate much air into the product. Therefore, the foam overrun was low and the bubble size small. Under these conditions, the water vapor generates high pressure, resulting in the formation of channels between bubbles, thus creating the pathways with low resistance for a very fast water vapor mass transfer. In addition, microwave freeze-drying experiments using a pilot plant unit were conducted to validate the findings of the freeze-drying microscope. A reduction of the drying time from 150 min (10% MD) to 78 min (40% MD) was achieved. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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19 pages, 12413 KiB

Open AccessFeature PaperArticle

Comparison of Techniques to Control Ice Nucleation during Lyophilization

by Jacob Luoma, Erika Ingham, Carmen Lema Martinez and Andrea Allmendinger

Processes 2020, 8(11), 1439; https://0-doi-org.brum.beds.ac.uk/10.3390/pr8111439 - 11 Nov 2020

Cited by 9 | Viewed by 2624

Abstract

Controlling ice nucleation during lyophilization of parenteral drug products increases the homogeneity of critical quality attributes, such as residual moisture, across drug product batches and shortens lyophilization cycle time. In the present study, we compare three mechanistically different techniques to control ice nucleation [...] Read more.

Controlling ice nucleation during lyophilization of parenteral drug products increases the homogeneity of critical quality attributes, such as residual moisture, across drug product batches and shortens lyophilization cycle time. In the present study, we compare three mechanistically different techniques to control ice nucleation during the freezing step of lyophilization, which are referred to as “depressurization”, “partial vacuum”, and “ice fog” techniques. The techniques are compared with respect to their operational limitations and challenges. Installation considerations are also discussed. Using the aforementioned nucleation techniques, we investigated a monoclonal antibody formulation and an enzyme formulation at different protein concentrations using feasible nucleation temperatures and different vial formats and fill volumes. Samples were compared for solid state properties and other critical quality attributes on stability. When nucleated at the same temperature, the three techniques produced products with the same quality attributes and stability behavior. Under conditions resulting in micro-collapse, stability behavior can be different. We found that each technology had considerations for achieving robust nucleation. The present comparison may serve as guidance in selecting a nucleation method. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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17 pages, 1208 KiB

Open AccessArticle

Economic Analysis of a Freeze-Drying Cycle

by Lorenzo Stratta, Luigi C. Capozzi, Simone Franzino and Roberto Pisano

Processes 2020, 8(11), 1399; https://0-doi-org.brum.beds.ac.uk/10.3390/pr8111399 - 02 Nov 2020

Cited by 38 | Viewed by 5861

Abstract

Freeze-drying has always been considered an extremely expensive procedure to dehydrate food or pharmaceutical products, and for this reason, it has been employed only if strictly necessary or when the high added value of the final product could justify the costs. However, little [...] Read more.

Freeze-drying has always been considered an extremely expensive procedure to dehydrate food or pharmaceutical products, and for this reason, it has been employed only if strictly necessary or when the high added value of the final product could justify the costs. However, little effort has been made to analyze the factors that make this technology so unaffordable. In this work, a model was proposed to calculate in detail the operational (OC) and capital costs (CC) of a freeze-drying cycle and an evaluation of the process bottlenecks was made. The main result is that the process itself, contrary to the classic belief, is not the most expensive part of freeze-drying, while the initial investment is the real limiting factor. Under this consideration, the optimization of a freeze-drying cycle should be formulated in order to fit more cycles in the lifespan of the apparatus, instead of merely reducing the power consumption of the machine. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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11 pages, 17303 KiB

Open AccessCommunication

Controlling Ice Nucleation during Lyophilization: Process Optimization of Vacuum-Induced Surface Freezing

by Andrea Allmendinger, Yuen Li Butt, Raphael Mietzner, Felix Schmidt, Joerg Luemkemann and Carmen Lema Martinez

Processes 2020, 8(10), 1263; https://0-doi-org.brum.beds.ac.uk/10.3390/pr8101263 - 08 Oct 2020

Cited by 4 | Viewed by 4228

Abstract

Biopharmaceuticals are often lyophilized to improve their storage stability. Controlling ice nucleation during the freezing step of the lyophilization process is desired to increase homogeneity of product properties across a drug product batch and shorten the primary drying time. The present communication summarizes [...] Read more.

Biopharmaceuticals are often lyophilized to improve their storage stability. Controlling ice nucleation during the freezing step of the lyophilization process is desired to increase homogeneity of product properties across a drug product batch and shorten the primary drying time. The present communication summarizes the process optimization of the freezing process when using vacuum-induced surface freezing to control ice nucleation, in particular for amorphous samples. We characterized freeze-dried samples for solid state properties, and compared these to uncontrolled nucleated samples using bovine serum albumin (BSA) as a model protein. Freezing parameters were optimized to obtain complete nucleation, adequate cake resistance during the subsequent lyophilization cycle, and elegant cakes. We highlight the challenges associated with vacuum-induced surface freezing and propose optimized freezing parameters to control ice nucleation, enabling manufacturing of amorphous samples. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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12 pages, 2611 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Freeze-Drying with Structured Sublimation Fronts—Visualization with Neutron Imaging

by Nicole Vorhauer-Huget, David Mannes, Mathias Hilmer, Sebastian Gruber, Markus Strobl, Evangelos Tsotsas and Petra Foerst

Processes 2020, 8(9), 1091; https://0-doi-org.brum.beds.ac.uk/10.3390/pr8091091 - 02 Sep 2020

Cited by 12 | Viewed by 4460

Abstract

The particular structure of the sublimation front in vacuum freeze-drying of porous media is, in most situations, not accessible at the pore scale. The classical measurement techniques access the process only globally. Knowledge about the structure of the front, however, is necessary for [...] Read more.

The particular structure of the sublimation front in vacuum freeze-drying of porous media is, in most situations, not accessible at the pore scale. The classical measurement techniques access the process only globally. Knowledge about the structure of the front, however, is necessary for prescriptive analysis of freeze-drying, as it dictates not only drying velocity, drying time, and overall energy consumption, but also the material properties after drying. This is especially relevant in situations in which the freeze-drying process is carried out close to the collapse temperature of the product. We, therefore, study the sublimation of ice with neutron tomography and analyze the spatial formation of the dry space using the example of frozen cylindrical maltodextrin with drying parameters at the limit of material collapse. We show that the sublimation front forms unique fractal structures that differ strongly from the usual form of a flat front. Distinct dry fingers covering the sample, in addition to a fractal peripheral sublimation front, were observed. The findings are important for the understanding of freeze-drying processes and will serve as a basis for the development of microscale models of freeze-drying. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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10 pages, 8987 KiB

Open AccessFeature PaperArticle

Development of a Freeze-Drying Stage for In-Situ µ-CT Measurements

by Mathias Hilmer, Sebastian Gruber and Petra Foerst

Processes 2020, 8(7), 869; https://0-doi-org.brum.beds.ac.uk/10.3390/pr8070869 - 18 Jul 2020

Cited by 2 | Viewed by 2865

Abstract

This paper shows the development of a freeze-drying stage for in-situ μ-CT measurements. The stage can operate in a temperature range of −40 °C up to 70 °C, and a pressure range from atmospheric pressure to 7 Pa at the sample holder. To [...] Read more.

This paper shows the development of a freeze-drying stage for in-situ μ-CT measurements. The stage can operate in a temperature range of −40 °C up to 70 °C, and a pressure range from atmospheric pressure to 7 Pa at the sample holder. To get the best visualization of the probe, it is fundamental that the materials around the sample holder are not absorbing most of the radiation. For this reason, we built an axial symmetrical stage built out of polyetheretherketon (PEEK). A test of the stage by different freeze-drying experiments with maltodextrin and sucrose particles and solutions demonstrated its suitability to visualize the freeze-drying processes in-situ. It was possible to track the drying front during the process by radiographic and tomographic measurements, as well as to visually resolve the ice crystals and porous structure in tomographic measurements. Using different samples and process parameters, we showed that the freeze-drying stage is not only suitable for in-situ µ-CT measurements, but also allows us to use the stage for other imaging methods such as neutron imaging, and for any sample where a controlled environment is needed. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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Review

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27 pages, 2774 KiB

Open AccessFeature PaperReview

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

by Merve B. Adali, Antonello A. Barresi, Gianluca Boccardo and Roberto Pisano

Processes 2020, 8(6), 709; https://0-doi-org.brum.beds.ac.uk/10.3390/pr8060709 - 19 Jun 2020

Cited by 61 | Viewed by 26580

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Modern Freeze Drying Design for More Efficient Processes)

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