Spray Freeze Drying Research Articles

Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.

Development of favipiravir dry powders for intranasal delivery: An integrated cocrystal and particle engineering approach via spray freeze drying

The therapeutic potential of pharmaceutical cocrystals in intranasal applications remains largely unexplored despite progressive advancements in cocrystal research. We present the application of spray freeze drying (SFD) in successful fabrication of a favipiravir-pyridinecarboxamide cocrystal nasal powder formulation for potential treatment of broad-spectrum antiviral infections. Preliminary screening via mechanochemistry revealed that favipiravir (FAV) can cocrystallize with isonicotinamide (INA), but not nicotinamide (NCT) and picolinamide (PIC) notwithstanding their structural similarity. The cocrystal formation was characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy, and unit cell determination through Rietveld refinement of powder X-ray analysis. FAV-INA crystalized in a monoclinic space group P21/c with a unit cell volume of 1223.54(3) Å3, accommodating one FAV molecule and one INA molecule in the asymmetric unit. The cocrystal was further reproduced as intranasal dry powders by SFD, of which the morphology, particle size, in vitro drug release, and nasal deposition were assessed. The non-porous flake shaped FAV-INA powders exhibited a mean particle size of 19.79 ± 2.61 μm, rendering its suitability for intranasal delivery. Compared with raw FAV, FAV-INA displayed a 3-fold higher cumulative fraction of drug permeated in Franz diffusion cells at 45 min (p = 0.001). Dose fraction of FAV-INA deposited in the nasal fraction of a customized 3D-printed nasal cast reached over 80 %, whereas the fine particle fraction remained below 6 % at a flow rate of 15 L/min, suggesting high nasal deposition whilst minimal lung deposition. FAV-INA was safe in RPMI 2650 nasal and SH-SY5Y neuroblastoma cells without any in vitro cytotoxicity observed. This study demonstrated that combining the merits of cocrystallization and particle engineering via SFD can propel the development of advanced dry powder formulations for intranasal drug delivery.

Electrostatic spray drying: Advantages for thermosensitive actives

Spray drying (SD) and freeze drying (FD) represent common methods utilized across various industries to achieve powdered final products. Electrostatic spray drying (ESD) is an emerging alternative as a continuous process to dry sensitive products without degradation, challenging the established drying techniques. This study aims to explore the efficacy of this process (ESD) in preserving the integrity of active components like oils, lactic acid bacteria (LAB), and enzymes. Additionally, a life cycle assessment (LCA) of these three drying technologies was conducted for a comprehensive evaluation. In oil encapsulation, the study showed that oxidation was significantly influenced by the formulation and the drying processes employed, where higher encapsulation efficiency resulted in lower degradation. This was observed, for instance, in the saponin composition dried with ESD. For LAB encapsulation, the results demonstrated higher preservation using FD and ESD. However, the impact of climate change using FD is twice superior to the ESD process. Finally, for enzyme application, β-gal activity was retained maximally while encapsulating using skim milk or maltodextrin. Specifically, regardless of drying technique, maltodextrin exhibited a maximum retention of β-gal activity, exceeding 30%. In all the case studies, ESD proved to excel in encapsulating thermosensitive actives, highlighting superior retention of native viability and properties compared to SD. Additionally, ESD generated results comparable to those achieved with FD. Therefore, ESD appears to be a promising method for high powder quality and a more sustainable process than FD and SD.

Development of dairy‐free soybean‐based yoghurt by active dry starter culture from kombucha: an investigation into microencapsulation, curd formation, protein and texture profiles during storage

SummaryIncreasing demand for the production and use of non‐dairy products has resulted from the rapid increase of vegetarian and lactose‐intolerant populations. In this study, non‐dairy yoghurt was developed from soybeans using microencapsulated starter culture consisting of Levilactobacillus brevis and Saccharomyces cerevisiae isolated from kombucha based on spray drying and freeze drying techniques using 20% maltodextrin (MD) and gum Arabic‐maltodextrin mixture (GA‐MD) as carriers. Scanning electron microscopy revealed high integrity and effective microbial protection within the carrier matrices, especially for freeze‐dried samples with L. brevis density being in the range of 6.1–6.4 log CFU/g. During 21‐day storage of microcapsules at 4 °C, L. brevis density decreased to 4.4–5.1 log CFU/g for all carriers while GA‐MD was incapable of preserving its viability at 30 °C. Meanwhile, the soybean‐based yoghurt was produced using these four microcapsules as active dry starter culture for the investigation of warm incubation/curd formation and subsequent refrigeration. Regarding warm incubation, in contrast to conventional yoghurt, there was no drop in pH or total acidity over the first 7–8 h of storage, followed by their sudden decline which led to the curd formation in the next hour at pH and total acidity of 5.42–5.75 and 2.29–3.06 g lactic acid/L respectively. Furthermore, GA‐MD samples exhibited more severe syneresis and surface cracks than MD during refrigeration in which the hardness and gumminess of yoghurt increased over time. Electrophoresis results also confirmed the proteolytic activity of lactic acid bacteria and yeast on β‐conglycinin and glycinin fractions of soy proteins.

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

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

Spray freeze dried uniform mannitol microspheres

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.

Physicochemical, structural characterization and evaluation of encapsulated hesperidin from natural sources: Comparison of two encapsulation techniques; spray drying and freeze drying

Freeze drying and spray drying techniques were evaluated for encapsulation of pure hesperidin and hesperidin from citrus peel extract in Maltodextrin and Gum Arabic in order to improve hesperidin stability and solubility. Physicochemical and structural properties of the microcapsules were determined and compared with the standardized high-purity hesperidin. Solubility of obtained microcapsules, defined by high WAI (0.202–0.697 g/g), WSI (88.02–99.746 %) and OAI (2.174–4.56 g/g), caused mainly by the amorphization of hesperidin structure was significantly improved. It was also confirmed with PXRD analyses. Microcapsules were of light colour, characterized by colour changes in the range from 12.57 to 47.49 and high whiteness index (64.12–94.45). The beneficial effect of encapsulation techniques is evident in flow properties where the Hausner ratio was in the range of 1.023–1.304 and Carr's index in the range of 2.26–23.273 %. Obtained microcapsules had satisfying hesperidin retention with encapsulation efficiency from 7.56 to 65.29 % and thermal stability above 110 °C. The best results were obtained for pure hesperidin encapsulated with freeze drying, satisfying results were obtained for citrus peel extract encapsulated in maltodextrin using spray drying. Obtained results indicate that the encapsulation of hesperidin can protect its bioactivities from environmental conditions and improve its solubility and flow properties, hence increasing its functional capabilities as pharmaceutical and cosmetic ingredients or additives.

Tailoring Dry Microparticles for Pulmonary Drug Delivery: Ultrasonic Spray Freeze-Drying with Mannitol and Salbutamol Sulphate

Spray freeze-drying has emerged as a valid alternative to traditional spray drying to produce therapeutic dry microparticles. In particular, the spherical shape and high porosity of spray freeze-dried microparticles make them suitable for pulmonary drug delivery through dry powder inhalers. However, an appropriate particle size and fine particle fraction are required to guarantee lung deposition. This study used ultrasonic spray freeze-drying to generate dry microparticles composed of mannitol either alone or added with the bronchodilator salbutamol sulphate. The influence of the solid concentration and the feed flow rate on the particle size, morphology, surface area, porosity, and crystallinity was investigated. Growing particle size was observed, increasing the concentration and feed flow rate. Similarly, the addition of the drug led to a larger particle size and surface area. The in vitro simulation of drug deposition highlighted the dependence of the aerodynamic properties on the solid concentration and feed flow rate. Due to the lower density and particle geometric size, the highest fine particle fraction (26%) and smallest mass median aerodynamic diameter (4.4 μm) were reached at the lowest solid concentration and feed flow rate.

Microencapsulation of bioactive compound extracts using maltodextrin and gum arabic by spray and freeze-drying techniques

Microencapsulation techniques establish a protective barrier around a sensitive compound, reducing vulnerability to external influences and offering controlled release. This work evaluates microencapsulation of Brazilian seed known as pink pepper (Schinus terebinthifolius) extract incorporated with green propolis extract, (main propolis font from the South America native plant Baccharis dracunculifolia DC) to enhancement antioxidant activity through synergic interaction, comparing to the extracts individually. Four treatments were produced using maltodextrin and combined with gum arabic as encapsulating agent, employing two different microencapsulation technique applied (spray drying and freeze drying) to assess their impact on physicochemical properties. The incorporation of gum arabic into matrix yielded higher encapsulation efficiency values, exhibiting significant differences for both encapsulation techniques. Combining the two encapsulation agents afforded greater protection of the bioactive compounds, resulting in an increase of approximately 31 % in the inhibition of the DPPH● radical. In controlled release analysis, maltodextrin exhibits the best protective effect on total phenolic compounds during intestinal release, whereas combining maltodextrin and gum arabic enhanced protection during gastric phase. Microcapsules may contribute to the protection of important bioactive compound, possessing a wide range of applications such as flavors encapsulation in food industry, lipids, antioxidants and pharmaceutical industry for controlled drug release.

TAT decorated siRNA polyplexes for inhalation delivery in anti-asthma therapy

In this work, a novel protonable copolymer was designed to deliver siRNA through the inhalation route, as an innovative formulation for the management of asthma. This polycation was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)D,L-aspartamide (PHEA) first with 1,2-Bis(3-aminopropylamino)ethane (bAPAE) and then with a proper amount of maleimide terminated poly(ethylene glycol) (PEG-MLB), with the aim to increase the superficial hydrophilicity of the system, allowing the diffusion trough the mucus layer. Once the complexation ability of the copolymer has been evaluated, obtaining nanosized polyplexes, polyplexes were functionalized on the surface with a thiolated TAT peptide, a cell-penetrating peptide (CPP), exploiting a thiol-ene reaction. TAT decorated polyplexes result to be highly cytocompatible and able to retain the siRNA with a suitable complexation weight ratio during the diffusion process through the mucus. Despite polyplexes establish weak bonds with the mucin chains, these can diffuse efficiently through the mucin layer and therefore potentially able to reach the bronchial epithelium. Furthermore, through cellular uptake studies, it was possible to observe how the obtained polyplexes penetrate effectively in the cytoplasm of bronchial epithelial cells, where they can reduce IL-8 gene expression, after LPS exposure. In the end, in order to obtain a formulation administrable as an inhalable dry powder, polyplexes were encapsulated in mannitol-based microparticles, by spray freeze drying, obtaining highly porous particles with proper technological characteristics that make them potentially administrable by inhalation route.

Effect of Encapsulation Techniques on Aroma Retention of Pistacia terebinthus L. Fruit Oil: Spray Drying, Spray Freeze Drying, and Freeze Drying.

The primary aim of this investigation was to assess the impact of varying the ratio of gum arabic to maltodextrin and employing diverse encapsulation techniques on the properties of the powdered substance and the capacity to retain the aromatic attributes of terebinth fruit oil. Distinct ratios of gum arabic to maltodextrin (75:25, 50:50, and 25:75) were employed to fabricate oil-in-water emulsions. The utmost stability of the emulsion was realized at a gum arabic to maltodextrin ratio of 75:25, characterized by a minimal creaming index and an even and small-scale dispersion. The encapsulation techniques employed included spray drying (SD), spray freeze-drying (SFD), and freeze-drying (FD). These methodologies were compared based on encapsulation efficiency, desiccation yield, powder attributes, and the capacity to retain aroma. The encapsulation efficiencies were notably higher (>90%) in SD, particularly with the application of an ultrasonic nozzle and a two-fluidized nozzle (2FN), in contrast to those obtained through SFD and FD. Notably, SD employing an ultrasonic nozzle exhibited superior preservation of volatiles (73.19%) compared to FD (24.45%), SD-2FN (62.34%), and SFD (14.23%). Among the various components, α-pinene and linalool stood out with near-perfect retention rates, close to 100%.

The physicochemical properties, functionality, and digestibility of hempseed protein isolate as impacted by spray drying and freeze drying

Hempseed protein has gained increasing attention for its sustainability and nourishment. This study aimed to investigate the effects of spray drying and freeze drying on the physicochemical properties, functionality, and digestibility of hempseed protein isolate (HPI). Compared to undried-HPI, both drying techniques altered physicochemical and structural properties. Particularly, protein denaturation temperature increased in freeze-dried HPI (FD-HPI) and spray-dried HPI (SD-HPI) samples (∼90 °C) than in undried-HPI (82.5 °C). Lysine content decreased from 38.26 mg/g in undried-HPI to 35.03 and 33.18 mg/g in FD-HPI and SD-HPI, respectively. Results revealed the loss of 26 and 17 kDa bands after drying. Notably, FD-HPI exhibited higher emulsifying stability and oil-holding capacity than SD-HPI. While both FD-HPI and SD-HPI had higher digestibility than undried-HPI, a 50% reduction in the liberation of free α-amino groups after digestion was found. This study provided information regarding changes in HPI after drying, offering insights for HPI production and application in the food industry.

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

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.

Reducing total nitrogen and dimethyl sulfide content of dry malt extract powder via spray-freeze drying method

Abstract Dry malt extract (DME) is powder prepared by dehydrating the wort, which is mainly produced by spray drying on the market. In addition, the beer industry has problems with the nitrogen content of wort, which is not easily controlled, and with the undesired volatile dimethyl sulfide (DMS), which is caused unpleasant odors in beer. In this study, DME was prepared using spray-freeze drying (SFD) technology by comparing with freeze dried DME and spray dried DME. The results show that SFD can be used as a novel engineering technique to improve the physical properties of DME having a narrow particle size distribution as well as high solubility and flowability. The freezing process was found to migrate proteins to the droplet surface by elemental analysis, and the drying process partially modified the surface protein and SFD powder fragility characteristics to achieve the purpose of reducing nitrogen content in DME.

Evaluation of the Physicochemical Characteristics of a Blend Fruit Juice Powder Mixed with Lactiplantibacillus plantarum: A Comparison of Spray Drying and Freeze Drying

The physicochemical properties and the survival of Lactiplantibacillus plantarum mixed with blend of fruit juice powders dried by spray and freeze drying methods were investigated. A formula containing maltodextrin 14% and malt extract 6% as a carrier and juices of red grape 20.4%, mulberry 75.6%, and strawberry 4.0% along with the bacterium (Lpb. plantarum) with 3 × 10 9 CFU/mL were dried by spray drying and freeze drying methods, separately. The physicochemical properties including color attribute, nutritional properties of the powders such as antioxidant, and phenolic content were measured. Drying efficiency of freeze-dried was 80.48%, which was higher than the spray-dried powders (50.84%). The higher antioxidant (87.95) and total phenolic content (3032.6 mg GAE/L) was achieved by freeze drying technique; however, lower moisture content and flowability as well as higher solubility and bulk density were obtained for spray-dried powders. The survival of probiotics in freeze-dried powders was higher than the spray-dried powders which can be related to mild conditions. The study indicated that the juice powders are suitable carriers for Lpb. plantarum and constitute good alternatives to highly acidic fruit juices.

Nondestructive monitoring of freeze drying and spray freeze drying endpoint by temperature-pressure method

The determination of the drying endpoint is crucial for the success of the freeze-drying process. However, nondestructive determination methods of the freeze-drying endpoint are often not applicable in spray freeze-drying equipment and process. To address this issue, an integrated spray freeze-drying equipment was developed that atomizes and freezes materials in the drying room through an atomizer, and freezes the frozen particles in the same drying room for vacuum freeze-drying to achieve one-step drying to prepare freeze-dried powder. The temperature and pressure method is used for real-time nondestructive monitoring of the entire drying process while ensuring no pollution in the materials. Experimental studies using pure water and milk as typical materials showed that a heating temperature of 45 °C and a pressure drop to 4.4 Pa can be considered as the drying endpoint, applicable to the monitoring of spray freeze-drying process. The temperature pressure method can be used as a method for judging the sublimation endpoint of spray freeze-drying. The relationship between temperature and pressure of the drying chamber can reflect the dry basis water content of freeze-dried materials.

Screening of sugars and cyclodextrins as carriers in montelukast dry powder inhalers processed by spray freeze drying

The purpose of this study was to develop a site targeting montelukast sodium (MTK) microparticles as a respiratory drug delivery system using the spray freeze drying (SFD) process. A range of sugars and cyclodextrins (CDs) were screened as carrier in order to find compatible excipients for the preparation of dry powder inhalers (DPIs). The physical characteristics of collected powders were studied by scanning electron microscopy (SEM), laser light scattering, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The aerodynamic behavior of the particles was also assessed using twin stage impinge (TSI). In the presence of simple sugars as carriers, highly porous particles in irregular shapes were produced. The use of CDs resulted in the formation of spherical particles with high porosity. Among all carriers that were used during the preparation of powders, raffinose had the best aerodynamic behavior with a fine particle fraction (FPF) of 60 % in sugar groups, while the lowest FPF was related to trehalose as carrier. Powders containing CDs mostly showed proper aerodynamic behavior, especially in formulations containing alfa-cyclodextrin (A-CD), beta-cyclodextrin (β-CD), and highly branched cyclic dextrin (HBCD). Overall, data indicated that the CDs were excellent excipients for use with MTK for respiratory drug delivery.

Screening of Cyclodextrins in the Processing of Buserelin Dry Powders for Inhalation Prepared by Spray Freeze-Drying.

In this study, we prepared inhalable buserelin microparticles using the spray freeze-drying (SFD) method for pulmonary drug delivery. Raffinose as a cryoprotectant carrier was combined with two levels of five different cyclodextrins (CDs) and then processed by SFD. Dry powder diameters were evaluated by laser light scattering and morphology was determined by scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were utilized for the determination of crystalline structures. The aerodynamic properties of the spray freeze-dried powders were evaluated by twin stage impinger (TSI) and the stability of prepared samples was assessed under normal and accelerated conditions. The prepared powders were mostly porous spheres and the size of microparticles ranged from 9.08 to 13.53 μm, which are suitable as spray-freeze dried particles. All formulations showed amorphous structure confirmed by DSC and XRD. The aerosolization performance of the formulation containing buserelin, raffinose and 5% beta-cyclodextrin (β-CD), was the highest and its fine particle fraction (FPF) was 69.38%. The more circular and separated structures were observed in higher concentrations of CDs, which were compatible with FPFs. The highest stability was obtained in the formulation containing hydroxypropyl beta-cyclodextrin (HP-β-16. CD) 5%. On the contrary, sulfobutylether beta-cyclodextrin (SBE-β-CD) 5% bearing particles showed the least stability. By adjusting the type and ratio of CDs in the presence of raffinose, the prepared formulations could effectively enhance the aerosolization and stability of buserelin. Therefore, they can be proposed as a suitable career for lung drug delivery.

Solidification and oral delivery of biologics to the colon- A review

The oral delivery of biologics such as therapeutic proteins, peptides and oligonucleotides for the treatment of colon related diseases has been the focus of increasing attention over the last years. However, the major disadvantage of these macromolecules is their degradation propensity in liquid state which can lead to the undesirable and complete loss of function. Therefore, to increase the stability of the biologic and reduce their degradation propensity, formulation techniques such as solidification can be performed to obtain a stable solid dosage form for oral administration. Due to their fragility, stress exerted on the biologic during solidification has to be reduced with the incorporation of stabilizing excipients into the formulation. This review focuses on the state-of-the-art solidification techniques required to obtain a solid dosage form for the oral delivery of biologics to the colon and the use of suitable excipients for adequate stabilization upon solidification. The solidifying processes discussed within this review are spray drying, freeze drying, bead coating and also other techniques such as spray freeze drying, electro spraying, vacuum- and supercritical fluid drying. Further, the colon as site of absorption in both healthy and diseased state is critically reviewed and possible oral delivery systems for biologics are discussed.

Evaluating spray gelation and spray freeze drying as the granulation method to prepare oral tablets of amorphous drug nanoplex

Amorphous drug nanoplex represents one of the most promising solubility enhancement strategies of poorly-soluble drugs. Solubility enhancement capability of nanoplex hitherto has been demonstrated for nanoplex suspension and lyophilized/spray-dried nanoplex, but not for its oral tablets. Using ciprofloxacin as the model poorly-soluble drug, we investigated spray gelation (SG) of alginate and spray freeze drying (SFD) with cryoprotective mannitol, as the nanoplex’s granulation methods. Both granules were evaluated in terms of their morphology, physical form, flowability, drug content, preparation yield, dissolution profile, drug solubility enhancement, and storage stability. Subsequently, tablets of the granules were prepared and characterized in terms of their drug content uniformity, weight variation, friability, hardness, dissolution profile, and solubility enhancement. The results showed that nanoplex in SG granules was embedded in dense amorphous alginate matrix, while nanoplex in SFD granules was dispersed in porous crystalline mannitol particles. Despite their distinct morphology, physical form, and dissolution profile, the two granules exhibited similar drug solubility enhancements. Both granules were readily compacted into tablets with minimal changes in their dissolution and solubility enhancement after tableting. The present work demonstrated SG and SFD as viable granulation methods of nanoplex, with SG granules exhibiting superior flowability, stability, but lower yield.