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Using two-fluid nozzle for spray freeze drying to produce porous powder formulation of naked siRNA for inhalation.

Using two-fluid nozzle for spray freeze drying to produce porous powder formulation of naked siRNA for inhalation.

Liang W, Chow MYT, Chow SF, Chan HK, Kwok PCL, Lam JKW

Abstract

Spray freeze drying is an attractive technology to produce powder formulation for inhalation. It can be used to generate large porous particles which tend to aerosolize efficiently and do not aggregate readily. It also avoids material to be exposed to elevated temperature. In this study, we reported the use of two-fluid nozzle to produce spray freeze dried powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA powder was produced at various atomization gas flow rates. The particles produced were highly porous as examined with the scanning electron microscopy, and the structural integrity of the siRNA was demonstrated with gel electrophoresis. The gene-silencing effect of the siRNA was also successfully preserved in vitro. The best performing siRNA formulation was prepared at the highest atomization gas flow rate investigated with a moderate FPF of 30%. However, this was significantly lower than that obtained with the corresponding hsDNA counterparts (FPF ∼57%). A direct comparison between the hsDNA and siRNA formulations revealed that the former exhibited a lower density, hence a smaller aerodynamic diameter despite similar geometric size.

Keywords

Gene silencing; Next generation impactor; Pulmonary delivery; Spray freeze drying; siRNA

Processing of sintered and CVD coated SiC/CNFs thin composite tubes

Processing of sintered and CVD coated SiC/CNFs thin composite tubes

Mubina Shaik, Asit Kumar Khanra, Bhaskar Prasad Saha

Abstract

Silicon carbide (SiC) and its composite powders dispersed with 1–3 wt% carbon nano-fibres (CNFs) were spray freeze granulated to produce spherical granules with uniform composition. Powders were shaped to thin dense tubes for use in a harsh environment by cold isostatic pressing followed by pressureless sintering at 2150 °C for 1 h in argon and SiC coating by chemical vapour deposition (CVD) technique. The physical, microstructural and thermo – mechanical properties of the composite tubes were evaluated and compared with bare SiC tubes. Good dispersibility of CNFs and sintering additives in the matrix by spray freeze granulation processing technique resulted in more than 98.5% theoretical density of the composite tubes with superior mechanical properties. SEM & EBSD analysis show grains are platy and equiaxed in nature with many CNFs trapped at the triple points hindering the SiC grain growth which is also confirmed by TEM analysis. The thermal conductivity value of the composite was also found higher than bare SiC at all temperatures when measured up to 1000 °C due to uniform distribution of CNFs in the matrix.

Keywords

SiC composites, Spray freeze granulation, Cold isostatic pressing, Sintering, CVD

Drying Technologies for the Stability and Bioavailability of Biopharmaceuticals

Drying Technologies for the Stability and Bioavailability of Biopharmaceuticals

Fakhrossadat Emami, Alireza Vatanara, Eun Ji Park, Dong Hee Na

Abstract

Solid dosage forms of biopharmaceuticals such as therapeutic proteins could provide enhanced bioavailability, improved storage stability, as well as expanded alternatives to parenteral administration. Although numerous drying methods have been used for preparing dried protein powders, choosing a suitable drying technique remains a challenge. In this review, the most frequent drying methods, such as freeze drying, spray drying, spray freeze drying, and supercritical fluid drying, for improving the stability and bioavailability of therapeutic proteins, are discussed. These technologies can prepare protein formulations for different applications as they produce particles with different sizes and morphologies. Proper drying methods are chosen, and the critical process parameters are optimized based on the proposed route of drug administration and the required pharmacokinetics. In an optimized drying procedure, the screening of formulations according to their protein properties is performed to prepare a stable protein formulation for various delivery systems, including pulmonary, nasal, and sustained-release applications.

Keywords

Biopharmaceuticals, drying technology, protein stability, bioavailability, pharmacokinetics

Influence of process variables on physical characteristics of spray freeze dried cellulose nanocrystals

Influence of process variables on physical characteristics of spray freeze dried cellulose nanocrystals

Wissam Abdallah, Musa R. Kamal

Abstract

This study compares the characteristics of cellulose nanocrystal (CNC) agglomerates prepared using spray drying, freeze drying, and spray freeze drying. Moreover, the effect of the concentration of CNC in the initial aqueous dispersion (~ 0.5–10.0 wt%) on the morphology, particle size distribution, porosity and crystalline structure of the spray freeze dried CNC agglomerates were investigated. Scanning electron microscopy was used to characterize the morphology and particle size distribution, nitrogen adsorption–desorption isotherms were used to analyze the porous structure of the particles, and X-ray diffraction was used to analyze the crystalline structure of the particles. Spray drying of CNC resulted in 0.5–30 μm dense agglomerates of slightly deformed elliptical and mushroom cap shaped particles with no porous structure. Freeze drying resulted in large irregular shape flakes of various sizes ranging mainly between 150 and 350 μm. On the other hand, spray freeze drying of CNC from dilute suspensions (~ 0.5 wt%) resulted in larger (4–240 μm) light spherical particles that were highly porous (~ 110 times larger in BET surface area), with web-like inter-connected structure consisting of 10–30 nm thick nanofibrils. Increasing the concentration to 5 wt% produced slightly denser spherical particles (13–110 μm) with slightly less porous web-like structure.

Keywords

Cellulose nanocrystals, Spray freeze drying, Morphology, Particle size distribution, Porosity Crystallinity

Ultrasonic spray-freeze drying of partially purified microbial transglutaminase

Ultrasonic spray-freeze drying of partially purified microbial transglutaminase

Hilal Isleroglu, Izzet Turker, Mehmet Tokatli, Banu Koc

Abstract

Ultrasonic spray-freeze drying (USFD) was evaluated to produce partially purified microbial transglutaminase (mTGase) powder, and the effects of the process conditions (a nozzle frequency of 48–120 kHz and a flow rate of 2–8 ml/min) on enzyme activity and particle size were determined. Furthermore, the relative activity changes at each step of USFD and the behavior of the dried enzyme at extreme pH levels, high temperature and presence of the metal ions were investigated. Additionally, the final product produced by USFD and the powder produced by conventional freeze drying (CFD) were compared in terms of relative activities and physical properties. The results showed that atomizing conditions affected the particle size and, hence the enzyme activity. The enzyme activity was enhanced by ultrasonic atomizing at all conditions while most of the activity loss occurred in the drying step. The USFD provided higher enzyme activity, smaller particle size, better particle morphology and better reconstitution properties than CFD, which are explained by the ultrasonic atomizing and accelerated freezing steps of USFD. Also, the USFD sample preserved its stability in tough conditions, such as extreme pH levels, high temperature and the presence of metal ions better than the CFD counterpart.

Keywords

Spray-freeze drying, Ultrasonic atomization, Transglutaminase, Relative activity, Particle size

Encapsulation of cationic iridium(III) tetrazole complexes into a silica matrix: synthesis, characterization and optical properties

Encapsulation of cationic iridium(III) tetrazole complexes into a silica matrix: synthesis, characterization and optical properties

Ilaria Zanoni, Valentina Fiorini, Marcos Rosado, Belén Ballesteros, Maria Androulidaki, Magda Blosi, Simona Ortelli, Stefano Stagni, Michele Dondia and Anna Luisa Costa

Abstract

Herein we report the easy incorporation of brightly phosphorescent cationic iridium(III) tetrazole complexes into a silica based matrix via an easily scalable colloidal process. For this purpose, two cationic Ir(III) emitters bearing 5-aryl tetrazole ligands (R-CN4) were selected: blue [F2IrPTZ-Me]+ (C^N = F2ppy; N^N = PTZ-Me – 2-(2-methyl-2H-tetrazol-5-yl)pyridine) and red [IrQTZ-Me]+ (C^N = ppy; N^N = QTZ-Me – 2-(2-methyl-2H-tetrazol-5-yl)quinoline). The cationic complexes were readily adsorbed to negatively charged silica nanoparticles and trapped in the sol–gel matrix. The sol-to-solid phase transfer was performed by using an innovative spray-freeze-drying technique, leading to the formation of phosphorescent solid micro-granules. The structural and optical characterisation of the Ir(III) complexes together with SiO2 nanoparticles, nanosols (Ir@SiO2) and powders (Ir@SiO2 powders), revealed how the presence of the Ir(III)-based complexes did not alter the morphology of the colloidal silica or granulated phases. Moreover, the silica matrix did not interfere with the optical properties of the embedded complexes. The distribution of [F2IrPTZ-Me]+ and [IrQTZ-Me]+ in the spray-freeze-dried powders was qualitatively evaluated by fluorescence microscopy, revealing how the luminescent particles were homogeneously dispersed all over the silica matrix. Interestingly, in aqueous solution the release of complex [F2IrPTZ-Me]+ from the corresponding Ir@SiO2 powder is almost negligible, therefore suggesting that a strong interaction occurs between the host–silica matrix and the Ir(III) guest complex.

Spray freeze-dried monolithic silica aerogel based on water-glass with thermal superinsulating properties

Spray freeze-dried monolithic silica aerogel based on water-glass with thermal superinsulating properties

Yuelei Pan, Xudong Cheng, Ting zhou, Lunlun Gong, Heping Zhang

Abstract

In this study, silica aerogels were prepared using water-glass precursor based on two drying strategies, namely conventional freeze drying (C-FD) and spray freeze drying (S-FD). It was known that the pore structure of silica aerogel can be optimized uniformly based on S-FD method when tert-butyl alcohol is directly utilized as a solvent. As a result, silica aerogels obtained by the S-FD method are monolithic with high thermal stability and low thermal conductivity, showing a great potential of thermal insulation materials for high-temperature environment.

Keywords

Silica aerogels, Spray, Freeze drying, Thermal insulation, Thermal stability

Porous Microparticles Containing Raloxifene Hydrochloride Tailored by Spray Freeze Drying for Solubility Enhancement

Porous Microparticles Containing Raloxifene Hydrochloride Tailored by Spray Freeze Drying for Solubility Enhancement

Seyyed Pouya Hadipour Moghaddam, Sajjad Farhat, Alireza Vatanara

Abstract

Purpose: The goal of this study was to improve the solubility and dissolution behavior of Raloxifene Hydrochloride (RH) using Spray Freeze Drying (SFD) technique. Methods: For achieving this goal, series of samples containing RH with polyvinylpyrrolidone (PVP) or hydroxypropyl beta cyclodextrin (HPβCD) used as solubility enhancers were prepared and microparticles were formed via SFD. The resultant microparticles were physicochemically characterized. Morphology of the microparticles were observed using Scanning Electron Microscopy (SEM). High Performance Liquid Chromatography (HPLC) was used for analyzing the solubility and dissolution profile of the samples. Results: Fourier Transmission Infrared (FTIR) spectra showed that SFD processed compositions did not affect chemical structure of RH. SEM and Thermal Gravimetric Analysis (TGA) revealed that the fabricated spherical and highly porous microparticles were in amorphous state. SFD processed powders showed superior solubility and dissolution behavior; where, 80% of the drug was dissolved within 5 minutes. Conclusion: SFD method can be a promising alternative for enhancing the solubility of poorly water soluble compounds.

Keywords

Dissolution profile, Porous microparticles, Raloxifene, Solubility, Spray freeze drying

Spray-Freeze Drying: a Suitable Method for Aerosol Delivery of Antibodies in the Presence of Trehalose and Cyclodextrins.

Spray-Freeze Drying: a Suitable Method for Aerosol Delivery of Antibodies in the Presence of Trehalose and Cyclodextrins.

Pouya MA, Daneshmand B, Aghababaie S, Faghihi H, Vatanara A

Abstract

We aimed to prepare spray-freeze-dried powder of IgG considering physicochemical stability and aerodynamic aspects. Spray-freeze drying (SFD) exposes proteins to various stresses which should be compensated by suitable stabilizers. The competence of cyclodextrins (CDs), namely beta-cyclodextrin (βCD) and hydroxypropyl βCD (HPβCD), at very low concentrations, was investigated in the presence of separate mannitol- and trehalose-based formulations. Spray-freeze-dried preparations were quantified in terms of monomer recovery and conformation by size exclusion chromatography (SEC-HPLC) and Fourier transform infrared (FTIR) spectroscopy, respectively. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) were employed to identify the thermal characteristics of powders. Particle morphology was visualized by scanning electron microscopy (SEM). Aerodynamic behavior of powders was checked through an Anderson cascade impactor (ACI). Although all formulations protected antibody from aggregation during the SFD process (aggregation < 1%), mannitol-containing ones failed upon the storage (19.54% in the worst case). Trehalose-HPβCD incomparably preserved the formulation with fine particle fraction (FPF) of 51.29%. Crystallization of mannitol resulted in IgG destabilization upon storage. Although employed concentration of CDs is too low (less than 50:1 molar ratio to protein), they successfully served as stabilizing agents in SFD with perfect improvement in aerosol functionality. Graphical Abstract ᅟ.

Keywords

IgG; aerodynamic property; cyclodextrins; spray-freeze drying; stability; trehalose

Second day at Ceramics Expo 2018

– Homogeneous and spherical granules of your powders made by Freeze Granulation, many interesting and good discussions in our stand at Ceramics Expo 2018 in Cleveland OH.