Spray drying and nano spray drying as manufacturing methods of drug-loaded polymeric particles.

In this review, benefits and drawbacks of the process of spray drying and nano spray drying with regard to the manufacturing of polymeric particles for pharmaceutical applications are discussed. Spray drying has been used for many years in the food, chemical and pharmaceutical industries for converting liquids into solids, in order to form products of uniform appearance. The construction of spray dryer enables to atomize the liquid into small droplets, which ensures a large surface area for heat and mass transfer, and significantly shortens the processing. Each droplet dries to an individual solid microparticle of characteristic features that can be tailored by optimizing formulation variables and critical process parameters. Since spray drying technology is easy to scale up and can be used for drying almost any drug in a solution or suspension, there are numerous examples of products in clinical use, in which this process has been successfully applied to improve drug stability, enhance bioavailability or control its release rate. In recent years, nano spray drying technology has been proposed as a method for lab-scale manufacturing of nanoparticles. Such an approach is of particular interest at early stages of drug development, when a small amount of new chemical entities is available. Here, the nebulization technique is used for feed atomization, while laminar gas flow in the drying chamber ensures gentle drying conditions. Moreover, electrostatic collectors have gradually replaced cyclone separators, ensuring high effectiveness in producing solid nanoparticles, even if a small volume of the sample is processed.

Exploring the Nano Spray-Drying Technology as an Innovative Manufacturing Method for Solid Lipid Nanoparticle Dry Powders.

To take advantage of solid-state properties, the nano spray-drying (NSD) technique was investigated as an innovative one-step method to produce solid lipid nanoparticles (SLN) in the form of a dry powder starting from a lipid/leucine O/W emulsion. Compritol was chosen as wall-forming lipid. Rapamycin (Rp) was employed as a model drug to be loaded into SLN. Based on an initial screening, Lutrol F68 was chosen as surfactant and high-shear homogenization as an emulsification method. A two-level fractional factorial design and an extended factorial design were employed to determine critical factors and best preparation conditions. Compritol concentration, L-leucine/lipid ratio, and Lutrol F68 concentration resulted critical. Best conditions granted 51% yield, 3.2 µm L-leucine/SLN particle size, and a SLN population around 150 nm. All samples showed the presence of lipid aggregates. Material loss in the emulsification step was found responsible for SLN aggregation and low yield. The almost quantitative Rp loading increased SLN population span. Replacing compritol with cetyl palmitate produced aggregation of dry powders and SLN. Overall, NSD was found a fast method to produce SLN dry powders. More insightful assessment of the emulsification step and lipid property effects will be critical to the optimization of the NSD process. Hypotheses account for direct coupling of high-pressure homogenization with NSD for future successful development of this promising manufacturing method.

Nano spray-dried sodium chloride and its effects on the microbiological and sensory characteristics of surface-salted cheese crackers.

Reducing particle size of salt to approximately 1.5 µm would increase its surface area, leading to increased dissolution rate in saliva and more efficient transfer of ions to taste buds, and hence, perhaps, a saltier perception of foods. This has a potential for reducing the salt level in surface-salted foods. Our objective was to develop a salt using a nano spray-drying method, to use the developed nano spray-dried salt in surface-salted cheese cracker manufacture, and to evaluate the microbiological and sensory characteristics of cheese crackers. Sodium chloride solution (3% wt/wt) was sprayed through a nano spray dryer. Particle sizes were determined by dynamic light scattering, and particle shapes were observed by scanning electron microscopy. Approximately 80% of the salt particles produced by the nano spray dryer, when drying a 3% (wt/wt) salt solution, were between 500 and 1,900 nm. Cheese cracker treatments consisted of 3 different salt sizes: regular salt with an average particle size of 1,500 µm; a commercially available Microsized 95 Extra Fine Salt (Cargill Salt, Minneapolis, MN) with an average particle size of 15 µm; and nano spray-dried salt with an average particle size of 1.5 µm, manufactured in our laboratory and 3 different salt concentrations (1, 1.5, and 2% wt/wt). A balanced incomplete block design was used to conduct consumer analysis of cheese crackers with nano spray-dried salt (1, 1.5, and 2%), Microsized salt (1, 1.5, and 2%) and regular 2% (control, as used by industry) using 476 participants at 1wk and 4mo. At 4mo, nano spray-dried salt treatments (1, 1.5, and 2%) had significantly higher preferred saltiness scores than the control (regular 2%). Also, at 4mo, nano spray-dried salt (1.5 and 2%) had significantly more just-about-right saltiness scores than control (regular 2%). Consumers' purchase intent increased by 25% for the nano spray-dried salt at 1.5% after they were notified about the 25% reduction in sodium content of the cheese cracker. We detected significantly lower yeast counts for nano spray-dried salt treatments (1, 1.5, and 2%) at 4mo compared with control (regular) salt (1, 1.5 and 2%). We detected no mold growth in any of the treatments at any time. At 4mo, we found no significant differences in sensory color, aroma, crunchiness, overall liking, or acceptability scores of cheese crackers using 1.5 and 1% nano spray-dried salt compared with control. Therefore, 25 to 50% less salt would be suitable for cheese crackers if the particle size of regular salt was reduced 3 log to form nano spray-dried salt. A 3-log reduction in sodium chloride particle size from regular salt to nano spray-dried salt increased saltiness, but a 1-log reduction in salt size from Microsized salt to nano spray-dried salt did not increase saltiness of surface-salted cheese crackers. The use of salt with reduced particle size by nano spray drying is recommended for use in surface-salted cheese crackers to reduce sodium intake.

A robust self-regenerating graphene-based adsorbent for pharmaceutical removal in various water environments.

The presence of active pharmaceutical ingredients (APIs) in wastewater effluents and natural aquatic systems threatens ecological and human health. While activated carbon-based adsorbents, such as GAC and PAC, are widely used for API removal, they exhibit certain deficiencies, including reduced performance due to the presence of natural organic macromolecules (NOMs) and high regeneration costs. There is growing demand for a robust, stable, and self-regenerative adsorbent designed for API removal in various environments. In this study, we synthesized a self-generating metal oxide nano-composite (S-MGC) containing titanium dioxide (TiO2) and silicon dioxide (SiO2) combined with 3D graphene oxide (GO) to adsorb APIs and undergo regeneration via light illumination. We determined optimal TiO2:SiO2:GO compositions for the S-MGCs through experiments using a model contaminant, methylene blue. The physical and chemical properties of S-MGCs were characterized, and their adsorption and photodegradation capabilities were studied using five model APIs, including sulfamethoxazole, carbamazepine, ketoprofen, valsartan, and diclofenac, both in single-component and multi-component mixtures. In the absence of TiO2/SiO2, 3D graphene oxide (CGB) displayed better adsorption performance compared to GAC, and S-MGCs further improve CGB's adsorption capacity. This performance remained consistent in two complex water environments: aqueous solutions at varying NOM levels and artificial urine. TiO2 supported on the GO surface exhibits similar photocatalytic activity to suspended TiO2. In a continuous fixed-bed column test, S-MGCs demonstrated robust API adsorption performance that is maintained in the presence of NOM or urine, and can be regenerated through multiple cycles of adsorption and light illumination.

Nano-Spray-Dried Levocetirizine Dihydrochloride with Mucoadhesive Carriers and Cyclodextrins for Nasal Administration.

Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was composed of hydroxypropyl methylcellulose polymer, including LC as a zwitterion, after neutralization by NaOH, and XRD investigations verified its amorphous state. This and a sulfobutylated-beta-cyclodextrin sodium salt-containing sample showed crystal peaks due to NaCl content as products of the neutralization reaction in the solutions before drying. The average particle size of the spherical microparticles was between 2.42 and 3.44 µm, except for those containing a polyvinyl alcohol excipient, which were characterized by a medium diameter of 29.80 µm. The drug was completely and immediately liberated from all the samples at pH 5.6 and 32 °C; i.e., the carriers did not change the good dissolution behavior of LC. A permeability test was carried out by dipping the synthetic cellulose ester membrane in isopropyl myristate using modified horizontal diffusion cells. The spray-dried powder with ß-cyclodextrin showed the highest permeability (188.37 µg/cm2/h), as this additive was the least hydrophilic. Products prepared with other cyclodextrins (randomly methylated-beta-cyclodextrin, sulfobutylated-beta-cyclodextrin sodium salt and (hydroxypropyl)-beta-cyclodextrin) showed similar or slightly higher penetration abilities than LC. Other polymer excipients resulted in lower penetration of the active agent than the pure LC.

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 ± 11.50 mg gallic acid equivalents (GAE)/g dry extract and 1389.71 ± 97.33 µmol 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 ± 0.5 µm 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.

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.

Development of Vinpocetine-Loaded Nasal Polymeric Micelles via Nano-Spray-Drying.

In this present formulation study, vinpocetine-loaded nano-spray-dried polymeric micelles were developed via nano-spray-drying. Three different mucoadhesive excipients were applied in the studies, namely chitosan, hyaluronic acid and hydroxypropyl methylcellulose. In all cases, the formulations had a proper particle size and drug content after drying with spherical morphology and amorphous structure. After rapid dissolution in water, the polymeric micelles had a particle size around 100-130 nm, in monodisperse size distribution. The high encapsulation efficiency (>80%) and high solubilization (approx. 300-fold increase in thermodynamic solubility) contributed to rapid drug release (>80% in the first 15 min) and fast passive diffusion at simulated nasal conditions. The formulated prototype preparations fulfilled the demands of a low-viscosity, moderately mucoadhesive nasal drug delivery system, which may be capable of increasing the overall bioavailability of drugs administered via the auspicious nasal drug delivery route.

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.

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 9-12 min 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.

Topical Formulation of Nano Spray-Dried Levocetirizine Dihydrochloride against Allergic Edema.

Levocetirizine dihydrochloride active ingredient was microencapsulated using nano spray-drying technology for preparing microparticles containing topical gel against edema. Hydroxyl propyl methyl cellulose (HPMC) was used as a carrier polymer during spray drying. The active ingredient content of the nano spray-dried products was 52.81% (w/w) and 51.33% (w/w) for ex vivo and in vivo experiments, respectively, and the average particle size was 2.6 µm. X-ray diffraction analysis indicated an amorphous state of the active ingredient embedded in the amorphous matrix of the polymer. Dermal oil gels composed of Miglyol 812 gelated by Dermofeel viscolid included 5% (w/w) (for ex vivo) and 10% (w/w) (for in vivo) active ingredient without or with 0.05% (w/w) menthol penetration enhancer. Qualitative ex vivo penetration studies using a confocal Raman microscopic correlation mapping were executed on human abdominal skin. The results showed that the active ingredient was enriched in the epidermis and upper dermis layer of the skin using oleogel loaded with the nano spray-dried drug-HPMC composite. Menthol addition to the oleogel resulted in the concentration of levocetirizine in the dermis. In vivo tests were performed on a mouse model of croton oil-induced ear edema. Negative control and Fenistil-treated groups were compared using the prepared oil gels with and without menthol. Without penetration enhancer, 20 µL of our oil gel loaded with nano spray-dried levocetirizine dihydrochloride composite showed similar effectiveness to the same volume of Fenistil gel, while 5 µL menthol containing sample was sufficient to eliminate the skin irritation similarly to 20 µL Fenistil.

Obtaining and Characterizing Andean Multi-Floral Propolis Nanoencapsulates in Polymeric Matrices.

Propolis is a substance with significant anti-inflammatory, anticancer, and antiviral activity, which could be used more efficiently at the nano level as an additive in the food industry. The aim was to obtain and characterize nanoencapsulated multi-floral propolis from the agro-ecological region of Apurimac, Peru. For nanoencapsulation, 5% ethanolic extracts propolis with 0.3% gum arabic and 30% maltodextrin were prepared. Then, the mixtures were dried by nano spraying at 120 °C using the smallest nebulizer. The flavonoid content was between 1.81 and 6.66 mg quercetin/g, the phenolic compounds were between 1.76 and 6.13 mg GAE/g, and a high antioxidant capacity was observed. The results of moisture, water activity, bulk density, color, hygroscopicity, solubility, yield, and encapsulation efficiency were typical of the nano spray drying process. The total organic carbon content was around 24%, heterogeneous spherical particles were observed at nanometer level (between 11.1 and 562.6 nm), with different behaviors in colloidal solution, the thermal gravimetric properties were similar in all the encapsulates, the FTIR and EDS analysis confirmed the encapsulation and the X-ray diffraction showed amorphous characteristics in the obtained material; stability and phenolic compound release studies indicated high values of 8.25-12.50 mg GAE/g between 8 and 12 h, the principal component analysis confirmed that the flora, altitude, and climate of the propolis location influenced the content of bioactive compounds, antioxidant capacity, and other properties studied. The nanoencapsulate from the district of Huancaray was the one with the best results, allowing its future use as a natural ingredient in functional foods. Nevertheless, technological, sensory, and economic studies should still be carried out.

Particle Engineering by Nano Spray Drying: Optimization of Process Parameters with Hydroethanolic versus Aqueous Solutions.

Nano spray drying has emerged as an outstanding platform for engineering micro- and nanoparticles, with growing applications in various areas of drug delivery. As a new technology involving distinct technical design, parameters of the nano spray drying process are not fully elucidated. In a quality-by-design approach, the aim of the current study was to gain thorough understanding of critical determinants of product characteristics in the Büchi Nano Spray Dryer B-90. Following a factorial experimental design, a series of spray drying experiments were conducted to gain new insights into the influences of the inlet temperature, the spray solvent, and the solute concentration in the spray solution on the yield, the moisture content, and the particle size of the nano spray-dried powder material. Special consideration was given to the potential of using hydroethanolic in comparison with aqueous solvent systems and to particle engineering for pulmonary drug delivery. Lactose and mannitol, widely used as excipients in dry powder inhalation formulations, were used as model materials. Lactose and mannitol are known to spray dry in amorphous and crystalline forms, respectively. The yields of spray drying of lactose and mannitol amounted generally to 71.1 ± 6.6% w/w and 66.1 ± 3.5% w/w, respectively. The spray-dried materials exhibited generally a number-weighted median particle diameter of 1.6 ± 0.2 µm and a volume-weighted median particle diameter of 5.1 ± 1.0 µm. A detailed analysis of the results improved understanding of the interplay between process parameters in the Nano Spray Dryer. The results demonstrate that optimization of spray generation is the key to yield optimization. On the other hand, particle size is determined by the spray mesh pore size and the spray solution degree of saturation. Selection of an appropriate spray solvent and using spray solution additives could optimize spray flow. In parallel, the spray solvent and the solute concentration in the spray solution determine the degree of saturation. Guidance on optimization of particle engineering by nano spray drying is provided.

Synthesis and Characterization of Magnetic Composite Theragnostics by Nano Spray Drying.

Composites of magnetite nanoparticles encapsulated with polymers attract interest for many applications, especially as theragnostic agents for magnetic hyperthermia, drug delivery, and magnetic resonance imaging. In this work, magnetite nanoparticles were synthesized by coprecipitation and encapsulated with different polymers (Eudragit S100, Pluronic F68, Maltodextrin, and surfactants) by nano spray drying technique, which can produce powders of nanoparticles from solutions or suspensions. Transmission and scanning electron microscopy images showed that the bare magnetite nanoparticles have 10.5 nm, and after encapsulation, the particles have approximately 1 µm, with size and shape depending on the material's composition. The values of magnetic saturation by SQUID magnetometry and mass residues by thermogravimetric analysis were used to characterize the magnetic content in the materials, related to their magnetite/polymer ratios. Zero-field-cooling and field-cooling (ZFC/FC) measurements showed how blocking temperatures of the powders of the composites are lower than that of bare magnetite, possibly due to lower magnetic coupling, being an interesting system to study magnetic interactions of nanoparticles. Furthermore, studies of cytotoxic effect, hydrodynamic size, and heating capacity for hyperthermia (according to the application of an alternate magnetic field) show that these composites could be applied as a theragnostic material for a non-invasive administration such as nasal.

Development of extra-fine particles containing nanosized meloxicam for deep pulmonary delivery: In vitro aerodynamic and cell line measurements.

Pulmonary drug administration provides a platform for the effective local treatment of various respiratory diseases. Application of nano-sized active ingredients results in higher bioavailability because of their large specific surface area. Extra-fine dry powder inhalers reach the smaller airways, further improving therapeutic efficiency. Poorly water-soluble meloxicam was the selected active ingredient. We aimed to decrease the particle size into the nano range by wet milling and producing extra-fine inhalable particles via nano spray-drying. The diameter of the drug was reduced to 138 nm. The particle size of the dry products was between 1.1 and 1.5 µm, and the dispersed diameter was between 500 and 800 nm. Owing to the excipients (poly-vinyl-alcohol, leucine), the spray-dried particles presented nearly spherical morphology. The drug became partially amorphous. Thanks to the improved surface area, the solubility and the released and the diffused amount of the meloxicam increased in artificial lung media. The in vitro aerodynamic measurements showed that the leucine-containing formulations had outstanding fine particle fraction (FPF) deposition with 1.3 µm mass median aerodynamic diameter (MMAD). The aerodynamic particle counter test also proved the extra-fine aerodynamic particle size. The in vitro cell line experiments revealed the non-cytotoxicity of the products and the suppression of the interleukin concentration. Overall, the powders are suitable for deep pulmonary delivery and the local treatment of lung inflammations.

Nano Spray-Dried Drugs for Oral Administration: A Review.

Spray drying is an important technology that is fast, simple, reproducible, and scalable. It has a wide application range, that is, in food, chemicals, and encapsulation of pharmaceuticals. The technology can be divided into conventional spray drying and nano spray drying. The key advantage of nano spray drying is the production of drug-loaded nanosized particles for various drug delivery applications. The recent developments in nano spray dryer technology and the market launch of the Nano Spray Dryer B-90 by Büchi Labortechnik AG in 2009 enabled the production of submicron spray-dried particles. This review focuses on nanosized drug delivery systems intended for oral administration produced by nano spray drying. First, the nano spray drying concept, the basic technologies implemented in the equipment, and the effects of the various process parameters on the final dry submicron powder properties are presented. Then, the topics of new formulation strategies of oral drugs are highlighted with examples that have entered the research literature in recent years. Next, the subjects of direct conversion of poorly water-soluble drugs, encapsulation of drugs, and drying of preformed nanoparticles are considered. Finally, topics such as morphology, particle size, size distribution, surface analysis, bioavailability, drug release, release kinetics, and solid-state characterization (by differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, nuclear magnetic resonance) of oral drug delivery systems produced by nano spray drying are discussed. The review attempts to provide a comprehensive knowledge base with current literature and foresight to researchers working in the field of pharmaceutical technology and nanotechnology and especially in the field of nano spray drying.

Casein Micelles as Nanocarriers for Benzydamine Delivery.

The aim of the present work was to optimize the process parameters of the nano spray drying technique for the formulation of benzydamine-loaded casein nanoparticles and to investigate the effect of some process variables on the structural and morphological characteristics and release behavior. The obtained particles were characterized in terms of particle size and size distribution, surface morphology, production yield and encapsulation efficiency, drug-polymer compatibility, etc., using dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, and Fourier transformed infrared spectroscopy. Production yields of the blank nanoparticles were significantly influenced by the concentration of both casein and the crosslinking agent. The formulated drug-loaded nanoparticles had an average particle size of 135.9 nm to 994.2 nm. Drug loading varied from 16.02% to 57.41% and the encapsulation efficiency was in the range 34.61% to 78.82%. Our study has demonstrated that all the investigated parameters depended greatly on the polymer/drug ratio and the drug release study confirmed the feasibility of the developed nanocarriers for prolonged delivery of benzydamine.

Physico-Chemical, In Vitro and Ex Vivo Characterization of Meloxicam Potassium-Cyclodextrin Nanospheres.

Nasal drug delivery has many beneficial properties, such as avoiding the first pass metabolism and rapid onset of action. However, the limited residence time on the mucosa and limited absorption of certain molecules make the use of various excipients necessary to achieve high bioavailability. The application of mucoadhesive polymers can increase the contact time with the nasal mucosa, and permeation enhancers can enhance the absorption of the drug. We aimed to produce nanoparticles containing meloxicam potassium (MEL-P) by spray drying intended for nasal application. Various cyclodextrins (hydroxypropyl-ß-cyclodextrin, α-cyclodextrin) and biocompatible polymers (hyaluronic acid, poly(vinylalcohol)) were used as excipients to increase the permeation of the drug and to prepare mucoadhesive products. Physico-chemical, in vitro and ex vivo biopharmaceutical characterization of the formulations were performed. As a result of spray drying, mucoadhesive nanospheres (average particle size <1 µm) were prepared which contained amorphous MEL-P. Cyclodextrin-MEL-P complexes were formed and the applied excipients increased the in vitro and ex vivo permeability of MEL-P. The highest amount of MEL-P permeated from the α-cyclodextrin-based poly(vinylalcohol)-containing samples in vitro (209 µg/cm2) and ex vivo (1.47 µg/mm2) as well. After further optimization, the resulting formulations may be promising for eliciting a rapid analgesic effect through the nasal route.

Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device.

Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler® and the high resistance Handihaler® as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler® and the Handihaler®. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 ± 0.67% w/w and particle mass median aerodynamic diameters of down to 1.90 ± 0.20 µm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 ± 3.46% w/w and particle mass median aerodynamic diameters of down to 6.79 ± 0.82 µm. When leucine was used as an excipient, using 50% w/w rather than 25% w/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w/w (95% confidence interval = 6.40-12.73% w/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler® outperformed the Handihaler® as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w/w (95% confidence interval = 8.17-10.16% w/w).

Characterization of Oregano Essential Oil (Origanum vulgare L. subsp. hirtum) Particles Produced by the Novel Nano Spray Drying Technique.

Oregano essential oil (OEO), due to its wide variety of biological activities, could be a "green" alternative to chemical preservatives. On the other hand, the difficulties in its use or storage have turned researchers' interest in encapsulation strategies as a way to face stability and handling issues. Fabrication of OEO-loaded particles, using nano spray drying technique (NSD) and whey protein isolate-maltodextrin mixtures (1:1, 1:3) as wall materials appears to be a novel and promising strategy. The obtained particles were characterized in terms of volatile composition, encapsulation efficiency, and physicochemical, molecular, morphological, and antibacterial properties. The results confirmed that encapsulation of OEO using NSD achieved high levels of powder recovery (>77%) and encapsulation efficiency (>98%) while assisting in the retention of the main bioactive compounds. The partial replacement of WPI by MD significantly affected particles' physical properties. FTIR analyses revealed the possible structural stabilization of core and wall materials, while SEM verified the very fine size and spherical shape. Finally, antibacterial studies demonstrated their activity against Escherichia coli and Staphylococcus aureus, which is much stronger in comparison with that of pure OEO, proving the positive effect of NSD and particles' potential in future food applications.