News on how Freeze Granulation can improve our powder properties

Spray freeze drying as a novel drying process for the formulation of probiotic powders containing Lacticaseibacillus rhamnosus GG

A. Steegmans, M. Plitzko, B. Luy, S. Lebeer, F. Kiekens

Abstract

Spray freeze drying was evaluated as a drying process for the formulation and stabilization of probiotic powders This technology combines spray freezing into cold vapour followed by rotational bulk freeze drying, and was investigated to combine the benefits of both spray drying and freeze-drying. What sets this system apart from other studies using this technology, is that the feed suspension was sprayed into cooled atmosphere instead of spraying directly into liquid nitrogen. To ensure droplet formation, a rather more dripping than spraying technique known as laminar jet break up is used, whereas other spray freeze drying techniques use binary nozzles, single fluid pressure nozzles, ultrasonic nozzles or rotary nozzles. Moreover, the principles of rotatory freeze-drying were used for bulk lyophilization which results in freeze dried microparticles instead of a freeze dried cake. This study examined the parameters related to the spraying head and their impact on bacterial viability and powder particle size. Secondly, the feasibility of dynamic lyophilization by applying rotary freeze drying to the frozen substrate was studied. Furthermore, the powder density, flow and hygroscopic properties were monitored to assess the downstream processability for industrial manufacturing. Cell reduction of at least 1,0 log CFU/g was reported, with a maximum remaining cell concentration of 7,4 log CFU/g in the dried product. The particle size of the almost perfect microspheres ranged from 532 ± 35 µm using a 300 µm nozzle orifice and 739 ± 57 µm using a 400 µm nozzle orifice with a mean sphericity of 0,97. Hygroscopicity investigations reported a critical point at 40 % relative humidity where collapse of the microspheres occurred. The overall process yield was 92,1 ± 4,2 % on average.

Keywords:

Drying techniques; Formulation; Freeze drying; Lacticaseibacillus rhamnosus GG; Live biotherapeutic products; Lyophilisation; Probiotics; Spray freeze drying; Trehalose.

Stable and inhalable powder formulation of mRNA-LNPs using pH-modified spray-freeze drying

Koki Ogawa, Otowa Aikawa, Tatsuaki Tagami, Takaaki Ito, Kohei Tahara, Shigeru Kawakami, Tetsuya Ozeki

Abstract

A powder formulation for mucosal administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is expected to be useful for respiratory diseases. Although freeze-drying is widely used to obtain solid formulations of mRNA-LNPs, highly hydrosoluble cryoprotectants, such as sucrose are necessary. However, sucrose is not a suitable excipient for inhalation powders because of its hygroscopic and deliquescence properties. Spray freeze-drying (SFD) is a method to produce inhalable powder formulation. In this study, we prepared inhalable powder formulations of mRNA-LNPs without deliquescence excipients using pH-modified SFD, which strengthens the interaction between mRNA and ionizable lipids of LNPs by acidic pH modifier, leading to retention of the encapsulated structure of mRNA-LNPs even after SFD. Powdered mRNA-LNPs were suitable for inhalation, and mRNA was encapsulated in LNPs after SFD. The mRNA encapsulation efficiency and mRNA transfection efficiency of pH-modified SFD-mediated powdered mRNA-LNPs were higher than those of conventional SFD, although they were significantly lower than those of liquid intact mRNA-LNPs. However, after long-term storage, the powdered formulation of the mRNA-LNPs exhibited higher mRNA transfection efficiency than liquid mRNA-LNP. Powdered mRNA-LNPs also exerted their function in air–liquid interface cultivation and in vivo intratracheal administration. Collectively, the powder formulation of mRNA-LNPs especially prepared by SFD is expected to be applied for dry powder inhalers.

Keywords:

Spray freeze-drying, mRNA-LNPs, inhalable powder, Powdered mRNA-LNPs

Spray freeze dried uniform mannitol microspheres

Shen Yan, Shengyu Zhang, Xiao Dong Chen, Winston Duo Wu

Abstract

Spray freeze drying is an attractive technology for fabricating pharmaceutical powder, but it is still challenging to tailor the microparticle physical and chemical structure. Herein, a series of uniform mannitol microparticles with controllable morphology and crystal properties were successfully fabricated via a self-developed micro-fluidic jet spray freeze tower. The effects of feed solution composition and freezing temperature on microparticle size, morphology, surface architecture and crystal property were investigated to propose the particle formation mechanism. Freezing temperature showed more apparent effect on the microparticle characteristics with higher solid content (10 and 15 w/w%) in aqueous solution; Whereas the addition of ethanol as a co-solvent had a notable impact on microparticle morphology, concurrently perturbing the crystallization tendencies of mannitol. These results provide new insights for producing spray freeze dried pharmaceutical microparticles.

Keywords: Spray Freeze Drying

Spray-freeze-drying as emerging and substantial quality enhancement technique in food industry

Poornima Singh, Vinay Kumar Pandey, Rahul Singh, Aamir Hussain Dar

Abstract

Spray freeze drying is an emerging technology in the food industry with numerous applications. Its ability to preserve food quality, maintain nutritional value, and reduce bulk make it an attractive option to food manufacturers. Spray freeze drying can be used to reduce the water content of foods while preserving the shelf life and nutritional value. Spray freeze-drying of food products is a process that involves atomizing food into small droplets and then flash-freezing them. The frozen droplets are then placed in a vacuum chamber and heated, causing the liquid to evaporate and the solid particles to become a dry powder. Spray freeze drying has become a valuable tool for the food industry through its ability to process a wide range of food products. This review’s prime focus is understanding spray freeze-dried approaches and emphasizing their applicability in various products.

Keywords: Spray freeze drying, Food products, Shelf life, Fruits & vegetables

Spray Freeze Drying of Biologics: A Review and Applications for Inhalation Delivery

Susana Farinha, João V Sá, Paulo Roque Lino, Marco Galésio, João Pires, Miguel Ângelo Rodrigues, João Henriques

Abstract

Biopharmaceuticals have established an indisputable presence in the pharmaceutical pipeline, enabling highly specific new therapies. However, manufacturing, isolating, and delivering these highly complex molecules to patients present multiple challenges, including the short shelf-life of biologically derived products. Administration of biopharmaceuticals through inhalation has been gaining attention as an alternative to overcome the burdens associated with intravenous administration. Although most of the inhaled biopharmaceuticals in clinical trials are being administered through nebulization, dry powder inhalers (DPIs) are considered a viable alternative to liquid solutions due to enhanced stability. While freeze drying (FD) and spray drying (SD) are currently seen as the most viable solutions for drying biopharmaceuticals, spray freeze drying (SFD) has recently started gaining attention as an alternative to these technologies as it enables unique powder properties which favor this family of drug products. The present review focus on the application of SFD to produce dry powders of biopharmaceuticals, with special focus on inhalation delivery. Thus, it provides an overview of the critical quality attributes (CQAs) of these dry powders. Then, a detailed explanation of the SFD fundamental principles as well as the different existing variants is presented, together with a discussion regarding the opportunities and challenges of SFD as an enabling technology for inhalation-based biopharmaceuticals. Finally, a review of the main formulation strategies and their impact on the stability and performance of inhalable biopharmaceuticals produced via SDF is performed. Overall, this review presents a comprehensive assessment of the current and future applications of SFD in biopharmaceuticals for inhalation delivery.

Keywords:

biopharmaceuticals; formulation; inhalation delivery; particle engineering; spray freeze drying.

Granulation of fine eggshell powder to produce feedstock powder for binder jetting additive manufacturing: A feasibility study

Shakil Arman, Fahim Khan, Mostafa Meraj Pasha, Jackson Sanders, Zhijian Pei

Abstract

This paper explores the feasibility of granulating fine eggshell powder using spray freeze drying to produce feedstock powder for binder jetting additive manufacturing. Fine eggshell powder possesses carbon-capture potential but exhibits poor flowability, causing issues during powder spreading in binder jetting additive manufacturing processes. This study demonstrates, for the first time, that spray freeze drying effectively converts fine eggshell powder into spherical granules without altering their chemical composition. Granulated eggshell powder was successfully produced using a solid loading (percentage of eggshell powder in the slurry used in granulation) of 30 % (by volume), a spraying pressure of 0.25 bar, and a feed rate of 0.5 L/hr. The granulation process significantly improved powder flowability. Additionally, the specific surface area of the granules was higher than that of the fine eggshell powder.

Keywords: Flowability, Spray Freeze Granulation, fine eggshell powder, binder jetting

A Comprehensive Review of the Latest Trends in Spray Freeze Drying and Comparative Insights with Conventional Technologies

Maria Ioannou Sartzi, Dimitrios Drettas, Marina Stramarkou and Magdalini Krokida

Abstract

Spray freeze drying (SFD) represents an emerging drying technique designed to produce a wide range of pharmaceuticals, foods, and active components with high quality and enhanced stability due to their unique structural characteristics. This method combines the advantages of the well-established techniques of freeze drying (FD) and spray drying (SD) while overcoming their challenges related to high process temperatures and durations. This is why SFD has experienced steady growth in recent years regarding not only the research interest, which is reflected by the increasing number of literature articles, but most importantly, the expanded market adoption, particularly in the pharmaceutical sector. Despite its potential, the high initial investment costs and complex operational requirements may hinder its growth. This paper provides a comprehensive review of the SFD technology, highlighting its advantages over conventional drying techniques and presenting its latest applications focused on pharmaceuticals. It also offers a thorough examination of the principles and the various parameters influencing the process for a better understanding and optimization of the process according to the needs of the final product. Finally, the current limitations of SFD are discussed, and future directions for addressing the economic and technical barriers are provided so that SFD can be widely industrialized, unlocking its full potential for diverse applications.

Keywords:

atomization; freezing; sublimation; encapsulation; pharmaceuticals; spray drying; freeze drying Spray freeze drying

Porous silicon nitride–based drug delivery carrier

Michal Hičák, Ľubomír Medvecký, Miroslav Hnatko, Radoslava Stulajterová, Mária Giretová, Monika Tatarková, Zoltán Lenčéš, Pavol Šajgalík

Abstract

Tetracalcium phosphate/monetite biocement was modified with the addition of 30 wt% highly porous silicon nitride/α-tricalcium phosphate (α-TCP) microgranules. The volume ratio of Si3N4 and α-TCP in microgranules was 1:1 and showed good in vitro simulated body fluid bioactivity with precipitation of hydroxyapatite particles. The intention of addition of microgranules to the biocement was to have a carrier of drug, which can be released into the body in due time. Granules prepared by the freeze granulation of starting mixture of silicon nitride and calcium phosphate and subsequent sintering at 1100°C have a suitable pore structure for the foreseen use. The pore volume was almost 1000 mm3/g with the open porosity of 77 vol%. This porosity and the biocompatible composition of silicon nitride–based granules gave a chance to fabricate a suitable composite cement for dexamethasone (DMZ) drug release into the human body. An accelerated release of dexamethasone from composite cement was observed and the full amount of DMZ was released from the composite biocement after 10 days. The presented results are a good base to adjust the total drug release time by the mixing of an appropriate amount of drug infiltrated ceramic granules with the tetracalcium phosphate/monetite cement.

Keywords

biocement, bioceramics, calcium phosphate, dexamethasone, drug release, silicon nitride

Physical properties of feeds for novel bioactives – encapsulating bead formation

Hansen, Mackenzie M.

Abstract

Encapsulation involves the entrapment of sensitive bioactive compounds with structure- forming food components to enhance protection and delivery. Blends of proteins and glass- forming carbohydrates are often used as encapsulation matrices and for structure formation. When bioactives intended for encapsulation are mixed with structuring proteins under acidic and neutral pH conditions and ambient temperatures, weak, non-covalent protein-bioactive interactions have been reported to occur. Complex formation may influence the physical properties of dispersions as well as dried products formed by feed mixtures. We hypothesized that: (i) Processes forming concentrated protein-carbohydrate feed dispersions into dry, solid beads could be developed, and (ii) formulation composition changes such as varied total solids, protein-carbohydrate ratios, protein isolates with different purities and structures, carbohydrate types, bioactives contents, and bioactives sources with diverse structures and sizes of predominant compounds would result in changes to the physico-chemical properties and drop formation abilities of dispersions, as well as the physical characteristics of dry beads formed. Key objectives of the present study were: (i) the development of two different simple, continuous processes forming feed dispersions into dried, novel bead structures, and (ii) characterization of the effects of changes in formulation compositions on the physical properties of liquid feeds and resulting dry beads.

Keywords

Protein, Bioactives, Encapsulation, Physico-chemical properties, Freeze granulation

Sintering and microstructure development of SFR MOX nuclear fuel

Julie Simeon

Abstract

For the manufacture of FNR (Fast Neutron Reactor) MOX (Mixed Oxide) fuel, (U,Pu)O2-x, consolidation of green compacts shaped from the raw powders, is performed by sintering at high temperature. Thus, the detailed study of the sintering is based on coupling of dilatometric tests in controlled reducing atmospheres to multi-scale microstructural characterizations in order to plot sintering maps and to establish predictive sintering models.In this study, three batches of powders were obtained by cryogenic granulation with target Pu/(U+Pu) contents of 15, 26 and 33 %mol. A single sintering trajectory was obtained from the relative density and grain size of each sample (raw and sintered). It is independent not only of the heat cycle (heating rate, sintering temperature and soak time) but also of the plutonium content and the oxygen stoichiometry.A batch with a Pu/(U+Pu) content of 26 %mol was prepared by direct co-milling (based on an industrial method for nuclear fuel fabrication). The trajectory observed for this batch differs from that of the three others.For all batches (granulated and co-milled), calculations of the diffusion coefficients from dilatometry data and the sintering map show that the densification is governed by the self-diffusion of plutonium at the grain boundaries. Furthermore, transmission electron microscopy results, in agreement with results obtained by X-ray diffraction, electron microprobe and Raman spectroscopy, show that grain growth is controlled by grain boundaries.A single sintering trajectory allows the calculation of the densification activation energy through methods exploiting the data collected by dilatometry. Thus, the activation energy of densification is evaluated at 454 ± 64 kJ/mol for all batches resulting from freeze granulation and at 548 ± 33 kJ/mol for the co-milled batch. These values allow the establishment of predictive sintering models that were used to lower the maximum temperature and duration required during sintering without affecting the fuel with the specifications.

Keywords

Microstructure, Sintering, Nuclear Fuel