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Spray freeze dried niclosamide nanocrystals embedded dry powder for high dose pulmonary delivery

Shengyu Zhang, Shen Yan, Kangwei Lu, Shixuan Qiu, Xiao Dong Chen, Winston Duo Wu

Abstract

Based on the drug repositioning strategy, niclosamide (NCL) has shown potential applications for treating COVID-19. However, the development of new formulations for effective NCL delivery is still challenging. Herein, NCL-embedded dry powder for inhalation (NeDPI) was fabricated by a novel spray freeze drying technology. The addition of Tween-80 together with 1,2-Distearoyl-sn-glycero-3-phosphocholine showed the synergistic effects on improving both the dispersibility of primary NCL nanocrystals suspended in the feed liquid and the spherical structure integrity of the spray freeze dried (SFD) microparticle. The SFD microparticle size, morphology, crystal properties, flowability and aerosol performance were systematically investigated by regulating the feed liquid composition and freezing temperature. The addition of leucine as the aerosol enhancer promoted the microparticle sphericity with greatly improved flowability. The optimal sample (SF_{– 80}D-N₂₀L₂D₂T₁) showed the highest fine particle fraction of ∼47.83%, equivalently over 3.8 mg NCL that could reach the deep lung when inhaling 10 mg dry powders.

Keywords

Fine particle fraction, NCL-embedded dry powder for inhalation (NeDPI), Particle formation mechanism, Spray freeze drying, Structure-performance relationship

Crystal Size Dependence of the Photo-Electrochemical Water Oxidation on Nanoparticulate CaTiO3

Monika Klusáčková, Roman Nebel, Kateřina Minhová Macounová, Petr Krtil

Abstract

Nanocrystalline CaTiO₃ materials with controlled particle size were prepared using spray-freezing/freeze-drying approach utilizing gelatine as a structure-directing agent. The resulting materials show characteristic particle size between 19 and 60 nm. The shape of the nanocrystals changes from cube-like single crystal containing particles into less regular isometric particles. Prepared materials as identified by X-ray diffraction analysis are formed by orthorhombic perovskite with small admixture of cubic phase. The ratio of both perovskite phases is independent of the particle size or prevailing crystal shape. All prepared materials show n-semiconducting character with band gap of ca 3.6 eV. They also show photo-electrochemical activity in water oxidation in acid media if a bias greater than 400 mV with respect to the flat band potential is applied. The specific photo-electrochemical activity decreases with increasing specific surface area. This behavior is attributed to increased probability of the electron transfer at the illuminated CaTiO₃ surface facilitated by the surface states. The CaTiO₃ materials also generate significant amount of ozone upon illumination in oxygen saturated solutions. The tendency to form ozone increases with increasing particle size suggesting that the ozone formation is hindered on materials with large number of low dimensionality states (crystal edges and vertices).

Keywords

Calcium titanate, Photo-electrochemistry, Water oxidation, Ozone formation, Spray-freezing/freeze-drying synthesis

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

Strategies for stabilization and preservation of liposomes

Pintu Chowdhary, L. Mahalakshmi, Sayantani Dutta, J.A. Moses, C. Anandharamakrishnan

Abstract

The stabilization of liposomes is an important aspect for maintaining the integrity of liposome structure. The stability of liposomes reduces in terms of uncontrollable fusion, undesirable payload loss, short shelf life, and unexpected mixing. Additionally, liposomes undergo physical as well as chemical degradation, causing low efficiency and quality of the formulation, and also the possibility of product degradation with undesirable side effects. Various factors influence the stability of liposomes, such as temperature, pH, surface charge, and lipid composition. To overcome this, various approaches have been implemented to stabilize them. This chapter describes various methods of liposome stabilization, such as surface modification, stabilizing membrane, changing lipid composition, and the addition of surfactants and nanoparticles. Furthermore, drying techniques such as freeze drying, spray drying, spray-freeze drying, electrohydrodynamic, and supercritical methods are also discussed for the preservation of liposomes.

Keywords

Drying techniques, Lipid composition, Stabilization, Surface modification

Development and performance evaluation of amorphous microencapsules containing lutein nanoparticles via antisolvent precipitation followed by spray/freeze-drying

Gang Zhang, Shihong Hu, Xiao Wang, Yanna Zhao, Min Liu, Jun Han, Sangeeta Prakash, Zhengping Wang, Zhuang Ding

Summary

This study developed nano-sized lutein-loaded solid microcapsules using antisolvent precipitation followed by spray/freeze-drying methods to improve chemical stability and dissolution efficiency. In antisolvent precipitation, lutein nanosuspensions with a particle size of 201.1 ± 4.3 nm were obtained with maltodextrin–Tween 80 as combined stabilisers. The effects of two drying methods on the performance characteristics of the microencapsulated powders were investigated. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analyses revealed the amorphous state of lutein and potential hydrogen bond interactions in the solid microcapsules. Stability testing showed that microencapsulation greatly reduced lutein loss (>80% plateau retention value (RV)) and retained the product colour (<1.5 ΔC) during long-term storage. The release behaviour of lutein in the microencapsulated powder was evaluated via dissolution studies, which indicated that the spray-dried microcapsules displayed faster and more complete dissolution behaviour (>90% within 10 min). In conclusion, an amorphous nanoparticle strategy based on antisolvent precipitation and spray-drying can be utilised to obtain commercially available lutein formulations with high stability and fast release.

Research Progress and Perspectives of Solid Fuels Chemical Looping Reaction with Fe-Based Oxygen Carriers

Yu Guan, Yinhe Liu, Xiaolong Lin, Bo Wang, Qiang Lyu

Abstract

Chemical looping (CL) is regarded as a promising technology in industrial applications, because of its inherent characteristic of CO₂ capture. The technique of CL is applied in solid fuels fields, including chemical looping combustion (CLC), chemical looping gasification (CLG), chemical looping reforming (CLR), chemical looping water splitting (CLWS), and oxygen carrier aided combustion (OCAC). Oxygen carrier is a core media in chemical looping reaction, which plays the role of transporting oxygen and has the function of decreasing the energy penalty of air separation. Among all oxygen carriers, iron-based (Fe-based) materials are of most possibilities to be applied in industrial field, because of its economical and eco-friendly characteristics. Some reviews have reported the Fe-based oxygen carrier in CL application. However, the related preparation methods, overall application of CL and theoretical reaction calculation of Fe-based oxygen carriers have not been covered comprehensively. In this Review, the general view of Fe-based oxygen carrier including iron ores and artificial synthesis are reviewed. In addition, the different synthesis methods of Fe-based oxygen carrier are meticulously and profoundly summarized, involving mechanical mixing, impregnation, spraying drying, freeze granulation, sol–gel, solution combustion, and coprecipitation method. Then, the characteristics of Fe-based oxygen carrier from the perspectives of thermodynamics, redox kinetics analysis, antisintering and wear property of iron oxides are discussed in detail. Furthermore, the chemical looping reaction mechanism of Fe-based oxygen carriers is reviewed from the perspectives of reaction and oxygen carrier migration mechanism. Moreover, this review summarizes the application of Fe-based oxygen carrier in CLC, CLG, CLR, CLWS, and OCAC. And the recent progress of reaction mechanism of oxygen carrier by density functional theory (DFT) calculations and machine learning are further presented. Finally, the challenges and prospects for Fe-based oxygen carrier with the corresponding effective strategies are proposed. It is expected that this Review may provide insights into the Fe-based oxygen carrier and the practical application of chemical looping.

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

Abstract

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.

Keywords

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

Book Description

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

Abstract

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 T_max (0.5–1.0 h) after oral administration of lyospheres® to rats (compared with T_max 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.

Keywords

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

Abstract

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.