Radio Frequency – Assisted Ultrasonic Spray Freeze Drying for Pharmaceutical Protein Solids
Tarun Tejasvi Mutukuri, Ahmad Darwish, Andrew David Strongrich, Dimitrios Peroulis, Alina Alexeenko, Qi (Tony) Zhou
This study examined physical stability of spray freeze dried (SFD) bovine serum albumin (BSA) solids produced using the radio frequency (RF)-assisted drying technique. BSA formulations were prepared with varying concentrations of trehalose and mannitol, using an excipient-free formulation as control. These formulations were produced using either traditional ultrasonic spray freeze drying (SFD) or RF-assisted ultrasonic spray freeze drying (RFSFD). The dried formulations were then characterized using Karl Fischer moisture content measurement, powder X-ray diffraction (PXRD), size exclusion chromatography (SEC), and solid-state hydrogen/deuterium exchange with mass spectrometry (ssHDX-MS). Moisture content did not have a good correlation with the physical stability of the formulations measured by SEC. ssHDX-MS metrics such as deconvoluted peak areas of the deuterated samples showed a satisfactory correlation (R2 = 0.914) with the SEC stability data. RFSFD improved the stability of formulations with 20 mg/ml of trehalose and no mannitol, and had similar stability with all other formulations as compared to SFD. This study demonstrated that RFSFD technique can significantly reduce the duration of primary drying cycle from 48.0 h to 27.5 h while maintaining or improving protein physical stability as compared to traditional lyophilization.
Spray freeze drying, Radio frequency spray freeze drying, Protein structure, Biopharmaceutical processing, Solid formulation
Spray-Freeze-Drying of Foods and Bioproducts: Theory, Applications and Perspectives
S. Padma Ishwarya
Spray-freeze-drying (SFD) is a synergistic drying technology that imbibes in it the merits of both spray drying and freeze-drying, whilst overcoming the limitations of these predecessor technologies. SFD produces uniquely powdered food and pharmaceutical products with porous microstructure and superior quality attributes. Owing to its atomization step and ultra-low-temperature operation, SFD is a competent drying technique for the production of valuable but sensitive bioactive components. Despite the costs and complexities involved, SFD has a competitive edge over the conventional drying techniques in providing distinctive product attributes. The applications of spray-freeze-drying in the area of food and bioproducts span across the product categories of instant food powders, dry flavors, active pharmaceutical ingredients, poorly water-soluble drugs, probiotics, proteins, enzymes and vaccines.
Spray-Freeze-Drying of Foods and Bioproducts: Theory, Applications and Perspectives is the first exclusive title on this interesting drying technique. It provides a comprehensive understanding of the fundamentals of SFD and its food and pharmaceutical applications.
The scope of this book, comprising 12 chapters, has been organizedunder four major headings: fundamentals of process-stages, applications with case-studies, recent advancements and the processing bottlenecks and solutions.
Rivaroxaban lyospheres prepared by a dimethyl sulfoxide-based spray-freeze-drying process
Jan Kožák, Claire Chrétien, Yann Pellequer, Alf Lamprecht
Spray-freeze-drying (SFD) processes are usually using aqueous solvent systems, which however, exclude the use of SFD for poorly water-soluble drugs/excipients. Here, we evaluated dimethyl sulfoxide for its suitability in formulating SFD particles (lyospheres®). Rivaroxaban was spray-freeze-dried from DMSO solutions containing polyvinyl pyrrolidone (PVP; Kollidon® 25), vinylpyrrolidone-vinyl acetate copolymer (PVP-VA; Kollidon® VA64) or polyvinyl alcohol 4–88 (PVA) forming porous lyospheres® (median particle size 250 to 350 µm). Rivaroxaban was amorphous with all three polymers, which in combination with the high porosity resulted in rapid dissolution in vitro within 10 min. Consequently, this translated in lower Tmax (0.5–1.0 h) after oral administration of lyospheres® to rats (compared with Tmax of 4 h with coarse rivaroxaban). Lyosphere formulations achieved a distinct bioavailability increase (AUC(0-inf) = 1487 ± 657 ng*h/ml with PVP; 4426 ± 1553 ng*h/ml with PVP-VA; 9569 ± 3868 ng*h/ml with PVA lyospheres®; whereas 385 ± 145 ng*h/ml with coarse rivaroxaban). These in vitro and in vivo results underlined the benefit of using DMSO in SFD that can broaden the applicability of the SFD process to a much larger repertoire of poorly water-soluble drugs/excipients.
Spray-freeze-drying, Dissolution-enhancement, Dimethyl sulfoxide, Rivaroxaban
Synthesis of hierarchical ZSM-5 microspheres with superior performance for catalytic methanol-to-olefin conversion
Yali Zhang, Kai Zhang, Chao Shang, Xiaoning Wang, Lei Wu, Guoqing Huang, Hao Wang, Qiming Sun, Xiao Dong Chen, Zhangxiong Wu
Methanol-to-olefin (MTO) conversion on zeolites has encountered severe coke deposition and rapid deactivation. Creating different levels of porosity is essential to mitigate such issues. Herein, we demonstrate a facile and green strategy to synthesize uniform and hierarchically macro/mesoporous ZSM-5 microspheres by combining spray-freeze drying and steaming-assisted crystallization (SAC). The structure, crystallinity, and porosity of the zeolite microspheres are controlled by adjusting the water/gel mass ratio and time in the SAC process. The structure evolution during the SAC process is revealed. In the catalytic MTO reaction, the representative hierarchically porous ZSM-5 catalyst exhibits superior catalytic performance. At a very high weight hourly space velocity of 18 h−1, it shows a dramatically prolonged lifetime (47 h at >99% conversion) and much-improved selectivity to ethylene and propylene compared with the conventional microporous ZSM-5 and nano-sized ZSM-5. The enhanced performance is originated from the hierarchical structure and suitable acidity of the ZSM-5 microspheres.
Nanoencapsulation of antioxidant peptides from Lupinus mutabilis in chitosan nanoparticles obtained by ionic gelling and spray freeze drying intended for colonic delivery
Arturo Intiquilla, Karim Jiménez-Aliaga, Amparo Iris Zavaleta, Alexander Gamboa, Nelson Caro, Mario Diaz, Martin Gotteland, Lilian Abugoch, Cristian Tapia
Oxidative stress has long been associated with the pathogenesis of inflammatory bowel disease (IBD), and it has been suggested that the combined administration of antioxidants and anti-inflammatory agents may be helpful for its treatment. Biopeptides from plant proteins, such as soybean glycinin tripeptide VPY, effectively inhibit pro-inflammatory mediators in intestinal epithelial and immune cells, which are both involved in the pathogenesis of IBD. This study aimed to produce antioxidant biopeptides from proteins of Lupinus mutabilis seeds and then encapsulate them in chitosan nanoparticles (NPs) for colonic delivery. An antioxidant peptide fraction of less than three kDa (UF3) was obtained and added at different concentrations (0.1–0.4 mg/ml) in chitosan solutions. The NPs were prepared by gelation with tripolyphosphate (CTPP-UF3) or spray freeze-drying of the chitosan solution (SFDC-UF3). Sizes of 332 ± 13 and 465 ± 58 nm and maximum encapsulation efficiencies of 63.80 and 71.75%, respectively, were obtained. UF3 maintained its antioxidant capacity (>80%) and showed different release profiles in 1X PBS buffer at pH 7.4, depending on the encapsulation method. FT-IR showed hydrogen bonding and electrostatic interactions between the peptide and chitosan. Both nanosystems maintained cell viability greater than 70% in colonic cell lines HT-29. These results show that both methods are appropriate for the nanoencapsulation of UF3 and can be used to design nanoparticles for colonic delivery.
Antioxidant, Peptidic fraction, Lupinus mutabilis, chitosan nanoparticles
Whey protein hydrolysates as prebiotic and protective agent regulate growth and survival of Lactobacillus rhamnosus CICC22152 during spray/freeze-drying, storage and gastrointestinal digestion
Hexiang Xie, Yang Liao, Meng Wai Woo, Hua Xiong, Qiang Zhao
Probiotic products are receiving increasing attention because of their tremendous beneficial health effects. However, it is still a great challenge to preserve probiotic viability during processing, storage and gastrointestinal digestion. Encapsulation is a widely known technology for enhancing bacterial viability and product stability. Hence highly hydrolyzed whey protein hydrolysate (HWPH) and moderately hydrolyzed whey protein hydrolysate (MWPH) used as a one-step culture medium and wall material for Lactobacillus rhamnosus were investigated.
H/MWPH-substitutive medium for the growth of Lactobacillus rhamnosus presented double the biomass production compared to other media. The H/MWPH-substitutive medium in combination with freeze drying also led to the highest survival ratio (97.13 ± 9.16%) and cell viability (10.62 log CFU g−1). The highest survival rate of spray-dried cells was 85.56 ± 7.4%. In addition, the cell viability of spray-dried Lactobacillus rhamnosus with MWPH as culture and dry medium was 0.79 log CFU g−1 higher than that of HWPH. Images confirmed that spray-dried Lactobacillus rhamnosus in MWPH provided better protection and it showed greater sustained viability after gastrointestinal digestion.
Overall, WPH just as carrier provides better thermal protection and MWPH is a preferable two-in-one medium for probiotics. © 2022 Society of Chemical Industry.
Grain size analysis and characterization by Raman spectroscopy of a homogeneous sintered MOX fuel
Marion Le Guellec, Florent Lebreton, Laure Ramond, Philippe Martin, Abibatou Ndiaye, Thierry Gervais, Guillaume Bernard-Granger
The grain size distribution of an U0.89Pu0.11O2 MOX fuel, sintered from a freeze-granulated powder to 97% of the theoretical density at 1700 °C during 4 h, for an oxygen potential set to − 387 kJ/mol, was investigated. The sintered microstructure is constituted by 8.5 vol% of clusters of small grains, having an average grain size around 1.5 µm, dispersed in a polycristalline matrix made of larger grains having an average grain size around 7–8 µm. Characterizations by Raman micro-spectroscopy showed that the Pu/(U+Pu) content was not the same depending on the type of grain. The large grains constituting the sintered polycrystalline matrix have a Pu/(U+Pu) content in the range 9.0–11.0 mol%, which is close to the overall target. The small grains agglutinated in the form of clusters are however clearly depleted in Pu.
Microstructure, Grain size, Raman spectroscopy, MOX
Spray-freeze-dried lyospheres: Solid content and the impact on flowability and mechanical stability
Annika Rautenberg, Alf Lamprecht
Handling low-density pharmaceutical products, such as lyophilisates, presents a challenge. Spray-freeze-dried (SFD) particles, overcoming many of these challenges, were analysed regarding flowability, mechanical stability, product properties (morphology, particle size) and physicochemical properties of the spraying solution (density, viscosity, freezing point, glass transition). Mannitol-polyvinylpyrrolidone 25 (PVP 25) solutions in concentrations ranging from 2.5 to 20% (w/w) were spray-freeze-dried with three different nozzle-diameters (25, 50, 100 μm). Results show it is not only possible to spray SFD solutions with various physicochemical properties (viscosity ≤3.07 ± 0.04 mPa·s, freezing point depravation ≤1.867 ± 0.058 °C) to produce a free-flowable powder but also the possibility to regulate median particle size via nozzle diameter and solid content of the solution (147–458 μm). All formulations containing at least 0.1 g/ml solid content exhibit a flowability comparable to commercially available excipients products with ten times higher densities, a good or passable flowability (angle of repose ≤40°) and no significant decrease in median particle size after mechanical stability testing (p ≥ 0.05), which can both be attributed to their high average sphericity (> 0.90). This shows that SFD is a suitable method to produce freeze-dried flowable products that maintain their mechanical stability.
Spray-freeze-drying, Lyospheres, Low-density powder
Characterization by electron probe microanalysis, Raman spectroscopy and transmission electron microscopy of a MOX fuel sintered from a freeze-granulated powder
Julie Simeon, Florent Lebreton, Laure Ramond, Philippe Martin, Doris Drouan, Catherine Sabathier, Guillaume Bernard-Granger
The microstructure of a 98.7 % dense U0.856Pu0.144O1.993 sintered sample (average grain size around 1.5 µm) has been characterized by electron probe microanalysis, Raman spectroscopy and transmission electron microscopy. Raman spectroscopy gives results comparable to electron probe microanalysis in terms of studying the spatial distribution of plutonium in a homogeneous sintered MOX fuel. The use of transmission electron microscopy allows additional characterizations of great interest for investigating the chemical homogeneity of sintered MOX fuels. At the scale of the elementary grains constituting the sintered polycrystal, a variation in the Pu/(U+Pu) content has been observed which can change typically from 0 to about 40 at% over a short distance (from 100 to 150 nm). Thereby, the thorough characterization of the microstructure of MOX fuels by transmission electron microscopy is a critical step to understand their genesis and to apprehend their dissolution properties with a view to their reprocessing.
Microstructure, EPMA, Raman spectroscopy, TEM, Oxides, MOX
Selectivity of Ru-rich Ru-Ti-O oxide surfaces in parallel oxygen and chlorine evolution reactions
Kateřina Minhová Macounová, Rebecca Katharina Pittkowski, Roman Nebel, Andrea Zitolo, Petr Krtil
The electrocatalytic behaviour of single-phase Ru1-xTixO2 materials was studied to outline general trends controlling the selectivity of oxide-based anodes in parallel oxygen evolution and chlorine evolution reactions. Materials with x ranging between 0 and 0.2 were prepared by spray freeze freeze drying approach. Prepared materials show a non-homogeneous distribution of Ti in the structure with dominant clustering of the Ti along the (001) direction. For materials with x higher than 0.1 the dominant linear clustering of Ti along the z-axis changes, including Ti clustering also along (111) direction. Prepared materials are active in both oxygen evolution and chlorine evolution reactions. The Ti has a pronounced effect on the selectivity of the prepared materials. Ti presence affects the selectivity of the prepared materials in a complex manner. Materials featuring a low Ti content (x∼0.05) retain a preference for oxygen evolution reaction even in presence of chlorides and are more selective for oxygen evolution than pure RuO2. The selectivity towards chlorine evolution increases with increasing Ti content and, apparently, also with clustering of Ti along the (111) direction. The selectivity towards chlorine evolution may be related to the tendency of the prepared catalysts to evolve the oxygen via lattice oxygen evolution reaction (LOER) reflecting the ability of the catalyst surface to form active sites under operando conditions.
Ru-Ti-O oxides, oxygen evolution, chlorine evolution, selectivity, local structure