News on how Freeze Granulation can improve our powder properties

ASEPTIC SPRAY FREEZE DRYING AS A TOOL FOR SUPPLY CHAIN FLEXIBILISATION

F. Kongoli, S. Buchmann, G. Imanidis, I. Karim, G. Kimura, G. Knipp, M. Makanga, N. Menshutina, P. Swaan, M. Tanner, H. Tarabishi

Abstract

Spray Freeze Drying (SFD) is an innovative lyophilization technology that is now entering industrial applications in lab, pilot and manufacturing scale for aseptic processing in pharmaceutical applications, as well as for the areas of medical devices, diagnostics and fine chemicals.

SFD applies the bulkware concept from solid dosage form processing to the area of aseptic freeze drying. It yields in highly homogeneous, free flowing bulkware which can be stored and accurately dosed. Filling is done after lyophilization, with a high degree of flexibility regarding dosing, primary packaging device design and unit number.
Accordingly, the supply chain becomes highly flexible and allows for patient centricity by even providing personalized medication, but also by bringing the required medication to the market or patient very fast.

In addition, product innovation potential is achieved by e.g. enabling to process high solid concentrations up to 40%, with still fast reconstitution characteristics of the lyophilized product. Furthermore, it allows for combinatory products by filling the various lyophilized compounds as required.

Many approaches have been taken to freeze material into particles for subsequent drying under cold condition. From dripping liquids directly into liquid nitrogen [1] to spraying in an cold air flow [2, 3].

The bulk freeze drying process can be carried out at atmospheric pressure (e.g. in a fluidized bed), in conventional freeze-dryers as a layer in trays, which are positioned on the shelfs or as shown here in a dynamic system with continous mixing to provide effecient mass and heat transfer. Drying at atmospheric pressure is feasible in lab scale but have been failing so far in the scale-up due to, in the frozen state, low glass transition temperature (Tg’). Vacuum freeze drying seems to be the gold standard. While tray freeze drying requires a lot of manual handling, which is especially difficult in the light of the recently published Annex 1 of the GMP guideline [4], dynamic freeze drying offers a contained processing with nearly no manual interference.required.

Keywords:

Spray freeze drying; Manufacturing Flexibility; Supply chain; Lyophilization; Freeze-drying

Lowering compaction pressure and sintering temperature of alumina using spray freeze granulation dried granules

Naoki Kondo1, Akihiro Shimamura, Mikinori Hotta, Junichi Tatami and Shinya Kawaguchi

Abstract

Spray drying (SD) and spray freeze granulation drying (SFGD) are the granulation processes of ceramic powder. Alumina green body made from SFGD granules via compaction has a relatively uniform structure without inter-granular pores, resulting in higher density and strength in the sintered body. This gives SFGD granules an advantage over SD granules. This study investigates the compaction pressure and sintering temperature of alumina granules produced by SD and SFGD. Using SFGD granules allows for the production of dense highstrength sintered alumina at lower compaction pressures and sintering temperatures. Even with higher compaction pressures applied to SD granules, the achieved sintered density falls short of that obtained with SFGD granules. These findings highlight the additional benefits of using SFGD granules over SD granules.

Keywords:

Spray drying, spray freeze granulation drying, alumina granule, Compaction pressure, Sintering temperature, Sintered density, Strength

Effect of spray freeze drying on the structural modification and rehydration characteristics of micellar casein powders

Jinbo Ren, Minjie Liao, Lingjun Ma, Fang Chen, Xiaojun Liao, Xiaosong Hu, Song Miao, John Fitzpatrick, Junfu Ji

Abstract

Micellar casein (MC) is usually spray-dried into powder form for transportation and storage. However, the micellar structure maintained by colloidal calcium phosphate (CCP) and hydrophobic forces leads to poor rehydration ability of MC powders, which limits its potential applications. Here, spray freeze drying (SFD) with controlled droplet size was used to produce MC powders. Their effects on the structure of MC and the subsequent rehydration characteristics including wetting, dispersion and dissolution were investigated. The results showed SFD powders obtained from smaller droplet size caused more than 50% of serum Ca2+ and PO43− to release from the micellar structure. These powder particles exhibited extremely high porosity (92%) and spherical morphology, which thus greatly shortened their wetting time. Furthermore, the smallest droplets during SFD were believed to produce the MC powders with the quickest dispersion and best solubility, as over 80% of the solids could be completely dissolved in just 15 min.

Keywords:

Spray freeze drying

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

Freezing behaviour and spray freeze granulation drying of silicon nitride slurries prepared from tert-butyl alcohol and cyclohexane solvent mixtures

Riko Yamazaki, Junichi Tatami, Motoyuki Iijima, Shinya Kawaguchi, Naoki Kondo

Abstract

A spray freeze granulation drying technique is suitable for obtaining soft and homogeneous granules, but the use of an aqueous slurry could degrade raw materials such as nitride. In this study, the freezing behaviour of silicon nitride slurries prepared from tert-butyl alcohol, cyclohexane, and their solvent mixtures was investigated, and granules were obtained from these slurries by the spray freeze granulation drying technique. An in situ optical coherence tomography observation of the freezing behaviour showed that the slurry from a solvent mixture of the eutectic composition froze in a single step in a shorter time than the other solvent mixtures. The solvent mixture of the eutectic composition yielded a homogeneous internal structure with fine pores in the freeze-dried body. The granules of that composition prepared by spray freeze granulation drying had a smaller size and a narrower size distribution, which resulted in a homogeneous internal structure of silicon nitride ceramics.

Keywords:

spray freeze granulation, freeze-drying

Spray freeze-drying for inhalable L-leucine, mannitol-based microparticles: The impact of process variables, L-leucine, and crystallinity on Aerosolization properties

Lorena Pasero, Adamo Sulpizi, Tomaso Guidi, Roberto Pisano

Abstract

In this study, microparticles carrying salbutamol sulphate were produced by pneumatic spray freeze-drying. The optimal particle size was assessed through a model, associated with a design of experiments. Growing solid concentrations and flow rate led to decreasing geometric diameters, while an opposite effect was associated with the feed flow rate. The aerodynamic diameter, instead, increased at increasing solid concentrations. Moreover, the role of crystallinity in determining the microparticles’ flowability was evaluated upon the incorporation of L-leucine. The addition of the amino acid induced the formation of two morphologies with different degrees of crystallinity. The absence of recrystallization significantly improved the aerosolization properties of the microparticles up to a maximum fine particle fraction (48 %) and a minimum mass median aerodynamic diameter (2 μm) at 10 % (w/w db) L-leucine. This result disclosed the influence of polymorphism on the microparticles’ cohesiveness, proving the dependency of the microparticles’ aerodynamics on L-leucine and mannitol crystallinity.

Keywords:

Spray freeze-drying, Inhalable microparticles, Inter-particle cohesiveness, Leucine, Polymorphism, Aerosolization

Effect of freeze drying and spray drying on physical properties, morphology and in vitro release kinetics of vitamin D3 nanoparticles

Iqra Bashir, Sajad Mohd Wani, Auqib Ahmad Bhat, Akhtar Ali Khan, Syed Zameer Hussain, Shaiq Ahmad Ganai, Nadira Anjum

Abstract

Encapsulation is a viable and effective technique for protection and stability of vitamin D3 during processing. In the present experiment, the effect of ultrasonication on encapsulation of vitamin D3 using gum arabic was studied. Nanoreduction of gum arabic emulsion largely increased the encapsulation profile of the process. Freeze drying and spray drying methods were employed for the drying of vitamin D3 nanoemulsions to obtain powdered encapsulates. Powders obtained by both techniques were analyzed in terms of physical properties, surface morphology, encapsulation efficiency and in vitro release kinetics. Parameters such as moisture content, product yield, encapsulation efficiency, particle size and zeta potential showed significant difference (p ≤ 0.05). While comparing release behavior, spray dried encapsulates presented better controlled release performance than freeze dried encapsulates. The findings revealed that spray drying technique present a better scope for encapsulating vitamin D3 due to its better encapsulation efficiency and release than freeze drying technique.

Spray freeze drying – A synergistic drying technology and its applications in the food industry to preserve bioactive compounds

Nisha Chhabra, Mehak Arora, Diksha Garg, Mahesh Kumar Samota

Abstract

In the food industry, drying is a crucial unit process for extending product shelf life. Many methods are available for drying of foods but spray drying and freeze drying have been widely adopted for industrial drying of a variety of heat-sensitive foods keeping in mind the drying efficiency as well as retention of nutritive components of foods. More recently a novel cutting-edge technique spray freeze drying (SFD) has started evolving in the food sector to accomplish this highly significant unit operation of drying. The advantages of traditional freeze-drying and spray-drying methods are combined in this process. This article explains various spray freeze-drying methods, both new and old, based on a number of factors, particularly the chilling medium and atomization settings. The method with freeze drying and spray drying is then compared, particularly in terms of the morphology and other significant characteristics of the final product obtained. The article also covers how this technology is used in the food sector to preserve bioactive compounds, which serves as confirmation for the comparison made above in terms of data pertaining to the obtained end goods. A brief description is given for its applications in food industry where it first evolved. The technology’s scope and potential difficulties have finally been briefly covered. The review was put together using data from roughly ten years’ worth of research and analysis in the area of this unique technology.

Keywords:

Spray freeze drying, freeze-drying, preserve bioactive compounds

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