Nano Spray Dryer Research Articles

Nanospray dryer assisted - Biogenic Synthesis of Graphene/Boron-Graphene Nanocomposites and their antibacterial efficacy

Nanospray dryer assisted - Biogenic Synthesis of Graphene/Boron-Graphene Nanocomposites and their antibacterial efficacy

Characterization of CNC Nanoparticles Prepared via Ultrasonic-Assisted Spray Drying and Their Application in Composite Films.

The ultrasonic-assisted spray dryer, also known as a nano spray dryer and predominantly used on a lab scale in the pharmaceutical and food industries, enables the production of nanometer-sized particles. In this study, the nano spray dryer was applied to cellulosic materials, such as cellulose nanofibrils (CNFs) and cellulose nanocrystals (CNCs). CNC suspensions were successfully dried, while the CNF suspensions could not be dried, attributable to their longer fibril lengths. The nano spray drying process was performed under different drying conditions, including nebulizer hole sizes, solid concentrations, and gas flow rates. It was confirmed that the individual particle size of nano spray-dried CNCs (nano SDCNCs) decreased as the nebulizer hole sizes and solid contents of the suspensions decreased. The production rate of the nano spray dryer increased with higher solid contents and lower gas flow rates. The resulting nano SDCNCs were added to a polyvinyl alcohol (PVA) matrix as a reinforcing material to evaluate their reinforcement behavior in a plastic matrix using solvent casting. After incorporating the 20 wt.% nano SDCNCs into the PVA matrix, the tensile strength and tensile modulus elasticity of the neat PVA nanocomposite film increased by 22% and 32%, respectively, while preserving the transparency of the films.

A design of experiment approach for optimized production of encapsulated trypsin using nano spray drying: Comparative physicochemical and kinetic characterization

Enzymes are challenging to formulate due to their inherent instability, particularly in solution. This study aims to use the design of experiment (DOE) approach to develop spray-dried encapsulated trypsin nano-powder (TrySP) with maximum activity and stability using a Büchi B-90 nano spray dryer. A 53 full factorial design with 26 randomly ordered experiments was created to study the impact of process variables on the quality attributes of TrySP. The additive concentration (%), mesh cap size (μm), inlet temperature (T inlet) (°C), trypsin concentration (%), and additive type (Mannitol or trehalose) were selected as the independent variables. The dependent parameters were yield value, particle size, residual enzyme activity, and moisture content. Further, comparative physicochemical and kinetic characterization of TrySP was performed. TrySP had diverse qualities (yield value 60.2–96.8%, residual activity >90–50%, particle size 314–1030 nm, and moisture content 0.7–2.2%). Optimized TrySP exhibited 89% yield value and 95% residual activity in the presence of 8% (w/w) mannitol. Kcat of TypSP increased from 22.5/s to 25.6/s with improved operational and storage stabilities. The half-life (t 1/2) of TrySP showed 6 folds increase. Furthermore, TrySP activation energy increased from 45,918 J/mol to 94,491 J/mol. The sustainable model presented in this study enables the development of a thermostable, encapsulated trypsin nano-powder with physical and chemical properties that are optimized for various biotechnological industrial applications.

Whey-pectin microcapsules improve the stability of grape marc phenolics during digestion.

Grape marc (GM) is an agri-food residue from the wine industry valuable for its high content of phenolic compounds. This study aimed to develop an encapsulation system for GM extract (GME) using food-grade biopolymers resistant to gastric conditions for its potential use as a nutraceutical. For this purpose, a hydroalcoholic GME was prepared with a total phenolics content of 219.62±11.50mg gallic acid equivalents (GAE)/g dry extract and 1389.71±97.33µmol Trolox equivalents/g dry extract antioxidant capacity, assessed through ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. Moreover, the extract effectively neutralized reactive oxygen species in Caco-2 cells, demonstrating an intracellular antioxidant capacity comparable to Trolox. The GME was encapsulated using whey protein isolate and pectin through nano spray drying (73% yield), resulting in spherical microparticles with an average size of 1±0.5µm and a polydispersity of 0.717. The encapsulation system protected the microcapsules from simulated gastrointestinal digestion (GID), where at the end of the intestinal phase, 82% of the initial phenolics were bioaccessible compared to 54% in the free GME. Besides, the encapsulated GME displayed a higher antioxidant activity by the ferric reducing antioxidant power assay than the free extract after GID. These results show the potential of this encapsulation system for applying GME as a nutraceutical with a high antioxidant capacity and protective effect against cellular oxidation.

Ketorolac Tromethamine Loaded Nano-Spray Dried Nanoparticles: Preparation, Characterization, Cell Viability, COL1A1 Gene Simulation and Determination of Anti-inflammatory Activity by In vivo HET-CAM Assay.

Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug from the heteroaryl acetic acid derivatives family. The most widely used new nanotechnological approaches for topical drug delivery are polymeric nanoparticles (NPs). Successful results have been obtained with low doses in many treatments, such as cancer, antimicrobial, pain, made with nanoparticle formulations of drug active ingredients. NPs were prepared using Nano Spray-Dryer. The cytotoxicity of the optimum formulation in BJ (ATCC® CRL-2522™) human fibroblast cells was determined by the WST- 1 method and the gene activity was elucidated by mRNA isolation and real-time polymerase chain reaction (RT-PCR). The in vivo HET- CAM assay was performed for anti-inflammatory activity. NPs presented PDI values lower than 0.5, and therefore particle size distribution was decided to be monodisperse. Positive zeta potential values of NPs highlighted the presence of the cationic ammonium group of Eudragit® RS 100. The release rates observed from KT-NP coded formulations after 24 hours were 78.4% ± 2.9, demonstrating extended release from all formulations, relative to pure KT. The lowest concentration of KT-NP increased fibroblast cell proliferation higher than the highest concentration of KT. The 5-fold increased effect of KT-NP formulation on collagen gene expression compared to KT is also related to the enhanced anti-inflammatory effect in line with the in vivo HET-CAM assay results. With the obtained cell viability, gene expression, and HET-CAM results, it has the hope of a successful nano-topical formulation, especially in both wound healing and anti-inflammatory treatment.

Investigation of Physico-Chemical Stability and Aerodynamic Properties of Novel "Nano-in-Micro" Structured Dry Powder Inhaler System.

Pulmonary drug transport has numerous benefits. Large surface areas for absorption and limited drug degradation of the gastrointestinal system are provided through the respiratory tract. The administration is painless and easy for the patient. Due to their better stability when compared to liquid formulations, powders have gained popularity among pulmonary formulations. In the pharmaceutical sector, quality assurance and product stability have drawn a lot of attention. Due to this, it was decided to perform a long-term stability study on a previously developed, nanosized dry powder inhaler (DPI) formulation that contained meloxicam. Wet milling was implemented to reduce the particle size, and nano spray-drying was used to produce the extra-fine inhalable particles. The particle diameter was determined using dynamic light scattering and laser diffraction. Scanning electron microscopy was utilized to describe the morphology. X-ray powder diffraction and differential scanning calorimetry were applied to determine the crystallinity. In an artificial lung medium, the in vitro dissolution was studied. The Andersen Cascade Impactor was used to investigate the in vitro aerodynamic characteristics. The stability test results demonstrated that the DPI formulation maintained its essential qualities after 6 and 12 months of storage. Consequently, the product might be promising for further studies and development.

Amorphization versus cocrystallization of celecoxib-tramadol hydrochloride using CO2-assisted nano-spray drying

The manipulation of both solid-state form and particle size is a versatile means by which physicochemical properties of pharmaceutical drugs may be improved/fine-tuned. The work presented herein describes the solid-state and particle size control of the most recently FDA-approved pharmaceutical cocrystal, composed of two APIs, Celecoxib-Tramadol hydrochloride (Seglentis®), using a continuous atomization technique, namely supercritical CO2-assisted nano-spray drying. Using a three-factorial design of experiments, both (co)amorphous and cocrystalline samples were generated, depending on processing conditions. Mean particle sizes ranged from 120 nm to 1160 nm, with solution flow rate showing the most significant effect due to its impact on atomized droplet sizes. While all (co)amorphous samples displayed a similar morphology, one set of conditions produced a (co)amorphous sample with a larger degree of intermolecular interactions, comparable with the hydrogen bonding network observed in the cocrystalline samples. Tabletting of four formulations was carried out to investigate the impact of particle size and solid-state on tabletability, compactability and compressibility. While all formulations performed adequately in these critical quality attributes, the formulations which contained cocrystalline particles underperformed regarding tabletability and compactability due to their irregular shape and larger size. However, due to the increased prevalence of intermolecular interactions, the cocrystalline and (co)amorphous samples with a larger degree of hydrogen bonding led to improved compressibility.

Nanoencapsulation of Phenolic Extracts from Native Potato Clones (Solanum tuberosum spp. andigena) by Spray Drying.

Native potato clones grown in Peru contain bioactive compounds beneficial to human health. This study aimed to optimize the spray-drying nanoencapsulation of native potato phenolic extracts utilizing a central composite design and response surface methodology, obtaining the optimal treatment to an inlet temperature of 120 °C and an airflow of 141 L/h in the nano spray dryer B-90, which allowed maximizing the yield of encapsulation, antioxidant capacity (DPPH), encapsulation efficiency (EE), total phenolic compounds, and total flavonoids; on the other hand, it allowed minimizing hygroscopicity, water activity (Aw), and moisture. Instrumental characterization of the nanocapsules was also carried out, observing a gain in lightness, reddening of the color, and spherical nanoparticles of heterogeneous size (133.09-165.13 nm) with a negative ζ potential. Thermal, infrared, and morphological analyses confirmed the encapsulation of the core in the wall materials. Furthermore, an in vitro release study of phenolic compounds in an aqueous solution achieved a maximum value of 9.86 mg GAE/g after 12 h. Finally, the obtained nanocapsules could be used in the food and pharmaceutical industry.

Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles.

Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood-brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.

Lactoferrin as a carrier of iron: Development and physicochemical characterization

Iron deficiency is the main cause of anemia, one of the most common nutritional deficiencies affecting millions of people worldwide. In addition, iron instability, sensitivity, and intense flavor limit its use in food fortification. In this work, lactoferrin (LF) particles were developed by Nano Spray Dryer (NSD) and its capacity to be used as an iron carrier was evaluated. The effect of NSD temperature (60 °C, 80 °C, and 100 °C) and LF concentrations (10 mg mL−1, 50 mg mL−1, and 100 mg mL−1) was evaluated on the LF structure and on the production and stability of a LF-iron carrier. Results showed that the NSD is suitable for producing LF particles with diameters ranged from 38.8 nm to 4533.6 nm. Although different surface morphologies were obtained, higher protein concentrations (100 mg mL−1) produced round shape and smooth surface particles, but for lower protein concentrations (10 mg mL−1 and 50 mg mL−1) wrinkled particles and doughnut shape particles were obtained. SDS-page electrophoresis and circular dichroism (CD) for secondary structure (185–260 nm) show that the characteristics of the structures were maintained, meaning that NSD does not cause protein degradation. CD for tertiary structure (250 nm–350 nm) and fluorescence tests confirmed the interaction between LF and iron, observed by an intensity decrease and a wavelength shift in fluorescence spectra. The CD tertiary structure analysis showed higher ellipticity for the Trp peak, meaning conformational changes in the neighbor amino acids due to protein-iron interaction. Iron release experiments were performed at different pH values (2.0 and 7.4) at 37 °C aiming to understand the release mechanism in different media. Results showed that at pH 2 the iron release could be described by the linear superposition model (Radj2 = 0.9879) (explained by Fick and relaxation phenomenon) and that at pH 7.4 there is no iron release, showing that particles are stable at neutral pH. NSD is a suitable technology for producing iron-loaded protein-based carriers that could be used in food applications.

Preparation and Characterization of Ibuprofen Containing Nano-Embedded-Microparticles for Pulmonary Delivery.

A fatal hereditary condition, cystic fibrosis (CF) causes severe lung problems. Ibuprofen (IBU), a non-steroidal anti-inflammatory drug, slows the progression of disease without causing significant side effects. Considering the poor water-solubility of the drug, IBU nanoparticles are beneficial for local pulmonary administration. We aimed to formulate a carrier-free dry powder inhaler containing nanosized IBU. We combined high-performance ultra-sonication and nano spray-drying. IBU was dissolved in ethyl acetate; after that, it was sonicated into a polyvinyl alcohol solution, where it precipitated as nanoparticles. Mannitol and leucine were added when producing dry particles using nano-spray drying. The following investigations were implemented: dynamic light scattering, laser diffraction, surface tension measurement, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, in vitro dissolution test, and in vitro aerodynamic assessment (Andersen Cascade Impactor). The particle diameter of the IBU was in the nano range. The spray-dried particles showed a spherical morphology. The drug release was rapid in artificial lung media. The products represented large fine particle fractions and proper aerodynamic diameters. We successfully created an inhalable powder, containing nano-sized IBU. Along with the exceptional aerodynamic performance, the ideal particle size, shape, and drug-release profile might offer a ground-breaking local therapy for CF.

Metal oxide encapsulated by 3D graphene oxide creates a nanocomposite with enhanced organic adsorption in aqueous solution.

The presence of organic contaminants (OCs) in aquatic systems is a threat to ecological and human health. Adsorption by graphene-based adsorbent is a promising technique for OC removal and we previously fabricated crumpled graphene balls (CGBs), via a novel nano-spray drying technique, which show robust adsorptive performance. Yet, since CGBs contain non-accessible surface area due to 2D graphene stacking, the goal of this research was to investigate the efficacy of maximizing the accessible CGB surface by synthesizing a nanocomposite composed of metal oxide nanoparticles encapsulated by crumpled graphene oxide (MGC). The metal oxides reduce graphene oxide stacking, expand the internal adsorptive surface area, and boost the adsorptive capacity of the MGC. MGC (fumed SiO2 or SiO2) exhibit an enhanced Langmuir adsorption capacity (qm, normalized by the % carbon) for an OC model, methylene blue (MB), achieving improvements of 60-86% compared to CGB, 3-4 fold compared to powder activated carbon (PAC) and 6-7 fold compared to granular activated carbon (GAC). MGCs display rapid adsorption reaching equilibrium after 9-12min of contact and remaining stable in wastewater effluent /surface water. A cost-efficiency comparison reveals MGCs achieve one ton of MB removal at similar or lower material costs than that of PAC/GAC.

Casein-Based Nanoparticles: A Potential Tool for the Delivery of Daunorubicin in Acute Lymphocytic Leukemia

The aim of this study was to develop casein-based nanoscale carriers as a potential delivery system for daunorubicin, as a pH-responsive targeting tool for acute lymphocytic leukemia. A coacervation technique followed by nano spray-drying was used for the preparation of drug-loaded casein nanoparticles. Four batches of drug-loaded formulations were developed at varied drug-polymer ratios using a simple coacervation technique followed by spray-drying. They were further characterized using scanning electron microscopy, dynamic light scattering, FTIR spectroscopy, XRD diffractometry, and differential scanning calorimetry. Drug release was investigated in different media (pH 5 and 7.4). The cytotoxicity of the daunorubicin-loaded nanoparticles was compared to that of the pure drug. The influence of the polymer-to-drug ratio on the nanoparticles' properties such as their particle size, surface morphology, production yield, drug loading, entrapment efficiency, and drug release behavior was studied. Furthermore, the cytotoxicity of the drug-loaded nanoparticles was investigated confirming their potential as carriers for daunorubicin delivery.

New water-based nanocapsules of poly(diallyldimethylammonium tetrafluoroborate)/ionic liquid for CO2 capture

Encapsulated ionic liquids as green solvents for CO2 capture are reported in this work. We present a novel combination of water-based poly(ionic liquid) and imidazolium-based ionic liquids (Emim[X]). Poly(diallyldimethylammonium tetrafluoroborate)/Emim[X] capsules were developed for the first time using Nano Spray Dryer B-90. Capsules were characterized by FTIR, SEM/EDX, TEM, TGA, DSC, CO2 sorption, and CO2/N2 selectivity, CO2 sorption kinetic and recycling were also demonstrated. Comparing the capsules reported in this work, the combination of poly(diallyldimethylammonium tetrafluoroborate) and the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (P[DADMA]/BF4) showed great potential for CO2 capture and CO2/N2 separation, providing higher results (53.4 mg CO2/g; CO2/N2 selectivity: 4.58).

Nose-to-brain delivery of galantamine loaded nanospray dried polyacrylic acid/taurodeoxycholate mixed matrix as a protective therapy in lipopolysaccharide-induced Alzheimer’s in mice model

One of the promising drug delivery approaches is performed by nanosizing the administered drug product using the nanospray drying technique. In this study, a combination of several formulation factors was integrated and exploited to augment the bioavailability of galantamine hydrobromide (GAL) via the intranasal route. Nanosized polymeric particles were fabricated using the mucoadhesive polymer, polyacrylic acid (PAA), and the permeability booster, sodium taurodeoxycholate (TDC). First, a preliminary study was conducted to adjust the nanospray drying conditions. Then, formulations were prepared on the basis of a mixed factorial experimental design and further analyzed using Design Expert® software. Different responses were investigated: particle size, polydispersity index, spray rate, drying efficiency, and percent yield. The optimized formulation was further assessed for physical morphology using the scanning electron microscope, flowability, in vitro drug release, and in vivo brain cell uptake using confocal laser scanning microscopy. The promising formulation (F6), composed of equal ratio of PAA and TDC and 20 mg GAL, exhibited a particle size of 185.55 ± 4.3 nm, polydispersity index of 0.413 ± 0.02, and yield-value of 69.58 ± 5.82 %. It also displayed good flowability, complete drug release within 2 h, and enhanced in vivo fluorescent dye uptake and penetration in brain cells. The efficacy of the optimized formulation was examined using lipopolysaccharide-induced Alzheimer’s in mice. Results revealed the advantageous influence of the optimized formulation (F6) through downregulation of NF-κβ, IL-1β and GFAP as well as upregulating TGF-1β in adult mice.

Nano Spray Dryer as an Advancement in Preparation of Nanoformulations: An Editorial

Nano Spray Dryer as an Advancement in Preparation of Nanoformulations: An Editorial

Synthesis and Investigation of the Properties of Al2O3–Y2O3 Powders Using Nanospray Drying

Synthesis and Investigation of the Properties of Al2O3–Y2O3 Powders Using Nanospray Drying

Novel quinizarin spray-dried nanoparticles for treating melanoma with photodynamic therapy

Melanoma is the most aggressive skin cancer. Moreover, it resists most of the currently available therapeutic protocols that aim to control its lethal progression. Photodynamic therapy (PDT) is a well-established photoprocess that can be used as co-adjuvant treatment to classic cancer treatment and surgery. Indeed, PDT is a minimally invasive procedure that exerts photoinduced and selective cytotoxicity against some types of cancer, including less aggressive types of skin cancer. Quinizarin (QZ), a dye, has been employed as a photosensitizer in PDT. However, this molecule is highly hydrophobic, which prevents its direct application under physiological conditions. In an attempt to solve this problem, we have prepared a novel Whey Protein and polymethyl methacrylate QZ-based nano-drug delivery system (QZ-PP-NP) by the layer-by-layer emulsion method combined with nanospray drying and characterized it in terms of size, particle distribution, zeta potential, and morphology. Then, we conducted biological tests on the cell lines fibroblastoids (NIH-3T3) and cancerous cells of melanocytic origin (B16-F10) in vitro, to find that application of QZ-PP-NP and PDT decreased cell viability to less than 5%.

Modelación de las condiciones de modificación de almidones para utilizarse como materiales de pared en la nano-encapsulación mediante secado por aspersión

In the present work, time-variable modeling of high-energy mechanical grinding (0, 20, 30, 40, 50, 60, 70, and 80 min), was carried out to obtain the best grinding conditions process for obtaining modified starches with applications as wall materials with favorable viscosity and particle size characteristics for the nano-encapsulation of bioactive compounds by means of nano-spray drying. The pasting profile was affected by the different mechanical grinding times, since the maximum viscosity (95 ºC) decreased as the grinding time increased, but this was not the case in the cooling stage (30 ºC) since at times of 30 and 40 min the viscosity was more significant than the maximum viscosity. The modified starches showed larger particle sizes compared to their native counterpart, indicating the formation of agglomerations. The model presents an adequate fit with respect to the experimental data and the feasible and infeasible conditions of this process are represented.

Designing a ‘Ready-to-Use’ powder formulation platform for the inhaled protein therapeutics

New biologics development coupled with an emerging biosimilars manufacturing scene are poised to stimulate growth in the biotechnology industry. Parenteral delivery, currently the mainstay of therapy, is often associated with pain, infection risks, high costs and poor patient compliance. Hence, non-invasive routes are preferred. The oral route is limited by low bioavailability, while the pulmonary route has been advocated as an attractive non-invasive yet efficacious alternative that could be applied for both local and systemic therapies. The dry powder inhaler (DPI), being a stable, convenient and non-invasive delivery device, is increasingly being considered for biologics delivery. However, balancing the concurrent demands for optimal aerosolization, bioactivity and stability is often difficult, requiring considerable expertise and development times. This work has therefore utilized the Taguchi experimental design to innovatively scrutinize several equipment and formulation parameters, and to propose and develop a ‘Ready-to-Use’ powder formulation platform which could be used to minimize development times and be applied as a useful starting template for biologics DPI development. Via the application of a model protein (lysozyme) and the following template conditions: Nano Spray Dryer, trehalose at 20% w/w, NaCl at 5% w/w and l-leucine at 15–20% w/w, fine particle fractions (FPFs) and bioactivities as high as 68.3 ± 2.3% and 95.2 ± 5.0%, respectively, were readily obtained. It was found that optimal FPF and bioactivity was less dependent on the spray dryer type, and more reliant on the type and concentration of protective and lubricating excipients. The powders obtained through this platform, exhibited strong aerosolization-promoting features in their particles (e.g. surface corrugation, hollow cavities), had particles with d50 of ∼2.30 ± 0.04 μm and were also stable to moisture-induced transformations. Potentially, this platform could be a useful precursor formulation suited to a variety of inhaled biomolecules, with just minor adaptations required for niche demands/applications.