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Ketoconazole (K) is a poorly water-soluble drug that faces significant challenges in achieving therapeutic efficacy. This study aimed to enhance the dissolution rate of ketoconazole by depositing spray-dried ketoconazole (SK) onto the surface of ground trehalose dihydrate (T) using spray drying. Ketoconazole-trehalose surface solid dispersions (SKTs) were prepared in ratios of 1:1 (SK1T1), 1:4 (SK1T4), and 1:10 (SK1T10), and characterized them using particle size analysis, scanning electron microscopy, powder X-ray diffraction, and in vitro dissolution studies. Results showed that the dissolution rates of the dispersions were significantly higher than those of pure ketoconazole, with the 1:10 ratio showing the highest dissolution rate. The improved dissolution was attributed to the formation of a new crystalline phase and better dispersion of ketoconazole particles. These findings suggest that the surface solid dispersion approach could be a valuable method for enhancing the bioavailability of poorly water-soluble drugs., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus ® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO 3 ) and ammonium bicarbonate (NH 4 HCO 3 ) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Hypericum perforatum (HP) contains valuable and beneficial bioactive compounds that have been used to treat or prevent several illnesses. Encapsulation technology offers protection of the active compounds and facilitates to expose of the biologically active compounds in a controlled mechanism. Microcapsulation of the hydroalcoholic gum arabic and maltodextrin have hot been used as wall materials in the encapsulation of HP extract. Therefore, the optimum microencapsulation parameters of Hypericum perforatum (HP) hydroalcoholic extract were determined using response surface methodology (RSM) for the evaluation of HP extract. Three levels of three independent variables were screened using the one-way ANOVA. Five responses were monitored, including total phenolic content (TPC), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), carr index (CI), hausner ratio (HR), and solubility. Optimum drying conditions for Hypericum perforatum microcapsules (HPMs) were determined: 180 °C for inlet air temperature, 1.04/1 for ratio of maltodextrin to gum arabic (w/w), and 1.98/1 for coating to core material ratio (w/w). TPC, antioxidant activity, CI, HR, and solubility values were specified as 316.531 (mg/g GAE), 81.912%, 6.074, 1.066, and 35.017%, respectively, under the optimized conditions. The major compounds of Hypericum perforatum (hypericin and pseudohypericin) extract were determined as 4.19 μg/g microcapsule and 15.09 μg/g microcapsule, respectively. Scanning electron microscope (SEM) analysis revealed that the mean particle diameter of the HPMs was 20.36 µm. Based on these results, microencapsulation of HPMs by spray drying is a viable technique which protects the bioactive compounds of HP leaves, facilitating its application in the pharmaceutical, cosmetic, and food industries., (© 2024. The Author(s).)

This study aimed to develop the solid astaxanthin-encapsulated self-microemulsifying delivery system (S-AST SMEDS) spray-dried particles and investigate the effect of materials in formulations on product characteristics. The optimized liquid AST SMEDS incorporated with a polymeric precipitation inhibitor (PI) was solidified with a solid carrier by spray drying. Physicochemical properties of S-AST SMEDS spray-dried powders including morphology, particle size and distribution, flowability, solid-state characters, moisture content, yield, loading capacity of AST, and reconstitution properties were examined. Polymeric PIs seemed to have an impact on particles' size, surface smoothness, and flowability while solid carriers had an effect on the particles' moisture content and droplet size of microemulsions obtained after reconstitution. The amount of AST encapsulated in S-SMEDS powder was influenced by both polymer and solid carriers. Dissolution and short-term stability of S-AST SMEDS were also studied. Our developed spray-dried solid SMEDS particles helped enhance AST dissolution rate., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Aqueous colloidal dispersions of water-insoluble polymers (APDs) avoid hassles associated with the use of organic solvents and offer processing advantages related to their low viscosity and short processing times. Therefore, they became the main vehicle for pharmaceutical coating of tablets and multiparticulates, a process commonly employed using pan and fluidized-bed machinery. Another interesting although less common processing approach is co-spray drying APDs with drugs in aqueous systems. It enables the manufacture of capsule- and matrix-type microspheres with controllable size and improved processing characteristics in a single step. These microspheres can be further formulated into different dosage forms. This systematic review is based on published research articles and aims to highlight the applicability and opportunities of co-spray drying drugs with APDs in drug delivery., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Gefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant (P < 0.05) increase in the ZD dissolution and release was observed from HPMC-based solid dispersion at pH 7.2 (up to 95% in 15 h), practically no drug was released at pH 1.2 and pH 6.5. Furthermore, the HPMC-based solid dispersions displayed enhanced mucoadhesive properties compared with PVP-based ones. Interestingly, cell viability studies using the neutral red assay showed that PVP and HPMC-based solid dispersions had no additional inhibitory effect on Caco-2 cell line compared to the pure drug., (© 2021. The Author(s).)

Galeterone, a novel prostate cancer candidate treatment, was discontinued after a Phase III clinical trial due to lack of efficacy. Galeterone is weakly basic and exhibits low solubility in biorelevant media (i.e., ~ 2 µg/mL in fasted simulated intestinal fluid). It was formulated as a 50-50 (w/w) galeterone-hypromellose acetate succinate spray-dried dispersion to increase its bioavailability. Despite this increase, the bioavailability of this formulation may have been insufficient and contributed to its clinical failure. We hypothesized that reformulating galeterone as an amorphous solid dispersion by KinetiSol® compounding could increase its bioavailability. In this study, we examined the effects of composition and manufacturing technology (Kinetisol and spray drying) on the performance of galeterone amorphous solid dispersions. KinetiSol compounding was utilized to create galeterone amorphous solid dispersions containing the complexing agent hydroxypropyl-β-cyclodextrin or hypromellose acetate succinate with lower drug loads that both achieved a ~ 6 × increase in dissolution performance versus the 50-50 spray-dried dispersion. When compared to a spray-dried dispersion with an equivalent drug load, the KinetiSol amorphous solid dispersions formulations exhibited ~ 2 × exposure in an in vivo rat study. Acid-base surface energy analysis showed that the equivalent composition of the KinetiSol amorphous solid dispersion formulation better protected the weakly basic galeterone from premature dissolution in acidic media and thereby reduced precipitation, inhibited recrystallization, and extended the extent of supersaturation during transit into neutral intestinal media., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The present study adopted a Quality by Design (QbD) approach to spray dry indomethacin nanosuspension (IMC-NS) consisting of HPC-SL, poloxamer 407, and lactose monohydrate. The Box-Behnken Design was used to systematically evaluate the effects of inlet temperature, aspiration rate, and feed rate on the critical quality attributes (CQAs) [redispersibility index (RDI; minimize), % yield (maximize), and % release at 15 min (maximize)] of the indomethacin spray dried nanosuspension (IMC-SD-NS). To identify significant main and quadratic effects, two-way interactions, and create a predictive model for the spray drying process, regression analysis and ANOVA were utilized. Following optimization, the IMC-SD-NS was analyzed for its physicochemical properties using X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. Statistical analysis revealed significant independent variables, including inlet temperature, feed rate, and aspiration rate, that critically impacted the solidified end product's RDI, % yield, and % release at 15 min. The models developed for critical quality attributes (CQAs) were significant at a p-value of 0.05. The crystalline state of IMC was maintained in the solidified product, as confirmed by XRPD, and no interactions were observed between IMC and the excipients as evaluated by FTIR. In vitro dissolution studies showed improved dissolution rate for the IMC-SD-NS (3.82-fold increase in overall drug release), which may be attributed to the readily redispersible nanosized drug particles. The implementation of a well-designed study, utilizing Design of Experiments (DoE) methodology, played a crucial role in the development of a highly effective spray drying process., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The aim of this study was to prepare HY-038 solid dispersions (SDs) with single carrier at high drug loading and then forming a tablet to enhance solubility, dissolution, and bioavailability via spray drying technology. At the same time, we hope to develop a more convenient in vitro method to predict the absorption behavior of different formulations in vivo. Different solid dispersions, varying in drug/polymer ratios, were prepared. Infrared spectroscopy, differential scanning calorimetry, scanning electron microscope, and X-ray diffraction were used to perform solid-state characterizations of the pure drug and SDs. Contact angle of water, dissolution in pH = 6.8 phosphate buffer, and in vivo absorption in dogs were studied. As a result, solid-state characterization demonstrated the transformation of the crystalline HY-038 to an amorphous state in the solid dispersions, and the in vivo exposure followed with the trend of the dissolution curve combined with contact angle. Compared with the prototype formulation, the C max and AUC 0-∞ of optimized formulation SD2 (HY-038-HPMCAS 3:1) increased by about 5 ~ 9 times at the same dose. More importantly, the SD2 formulation showed approximately linear increases in C max and AUC 0-∞ as the dose increased from 50 to 100 mg, while the prototype formulation reached absorption saturation at 50 mg. SD2 (HY-038-HPMCAS 3:1) was selected as the best formulation for the downstream development., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Abstract Nanoporous zirconia with high surface area and crystallinity has a wide range of industrial applications, such as in inorganic exchangers for ion exchange columns, catalyst substrates, and packing material for HPLC. Spherical particles of crystalline nanoporous zirconia are highly desired in various industries due to easy handling of the materials in a fluidized bed. Here, spray drying was adopted to produce spherical nanoporous zirconia powders in both laboratory scale and pilot plant scale. Effect of salts on spray-dried ZrO2 powders and their crystallization behavior was studied. It was found that addition of salts to the zirconia precursors has a huge effect on the crystallization of nanoporous zirconia powders. These results have a great impact on the development of microspheres of nanocrystalline ZrO2 and potentially open up a new opportunity to the low-cost production of porous ceramic microspheres with the salt templating method, in general.

To prevent the sticking of Corni fructus extract (CFE) during spray drying, the anti-sticking effects of different excipients were compared. Hydroxypropyl methylcellulose (HPMC)-VLV showed a higher powder yield at a lower dosage (8% of total solids), and a lower solution viscosity, compared with HPMC-E5. Therefore, HPMC-VLV is a more effective excipient for reducing CFE sticking during spray drying. The spray-drying process parameters were optimized by central composite rotatable design/response surface methodology, and spray drying was conducted under the following conditions: Inlet air temperature, 126 °C; atomization pressure, 1.05 bar; pump speed, 7.7 mL/min. Scanning electron microscopy showed that the powder comprised shrunken spherical particles with particle sizes in the range of 2-30 μm. Analysis of dynamic surface tension and chemical elements on the powder surface showed that HPMC-VLV rapidly moved to the droplet surface owing to its surface activity. HPMC covered the droplet surface and reduced surface tension, achieving an anti-sticking effect. In conclusion, HPMC-VLV at a solid content of 8% significantly improved the spray drying and reduced sticking of CFE. The spray-drying process parameters were nonlinearly related to the dry product yield. Graphical Abstract., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Spray-drying dispersion (SDD) is a well-established manufacturing technique used to prepare amorphous solid dispersions (ASDs), allowing for poorly soluble drugs to have improved bioavailability. However, the process of spray-drying with multiple factors and numerous variables can lead to a lengthy development timeline with intense resource requirements, which becomes the main obstacle limiting spray-drying development at the preclinical stage. The purpose of this work was to identify optimized preset parameters for spray-drying to support the early development of ASDs suitable for most circumstances rather than individual optimization. First, a mini-DoE (Design of Experiment) study was designed to evaluate the critical interplay of two key variables for spray-drying using a BUCHI B-290 mini spray dryer: solid load and atomizing spray gas flow. The critical quality attributes (CQAs) of the ASDs, including yield, particle size, morphology, and in vitro release profile, were taken into account to identify the impact of the key variables. The mini-DoE results indicated that a 5% solid load (w/v %) and 35 mm height atomizing spray gas flow were the most optimized parameters. These predefined values were further verified using different formulation compositions, including various polymers (Eudragit L100-55, HPMCAS-MF, PVAP, and PVP-VA64) and drugs (G-F, GEN-A, Indomethacin, and Griseofulvin), a range of drug loading (10 to 40%), and scale (200 mg to 200 g). Using these predefined parameters, all ASD formulations resulted in good yields as well as consistent particle size distribution. This was despite the differences in the formulations, making this a valuable and rapid approach ideal for early development. This strategy of leveraging the preset spray-drying parameters was able to successfully translate into a reproducible and efficient spray-drying platform while also saving material and reducing developmental timelines in early-stage formulation development., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Respiratory diseases are among the leading causes of morbidity and mortality worldwide. Innovations in biochemical engineering and understanding of the pathophysiology of respiratory diseases resulted in the development of many therapeutic proteins and peptide drugs with high specificity and potency. Currently, protein and peptide drugs are mostly administered by injections due to their large molecular size, poor oral absorption, and labile physicochemical properties. However, parenteral administration has several limitations such as frequent dosing due to the short half-life of protein and peptide in blood, pain on administration, sterility requirement, and poor patient compliance. Among various noninvasive routes of administrations, the pulmonary route has received a great deal of attention and is a better alternative to deliver protein and peptide drugs for treating respiratory diseases and systemic diseases. Among the various aerosol dosage forms, dry powder inhaler (DPI) systems appear to be promising for inhalation delivery of proteins and peptides due to their improved stability in solid state. This review focuses on the development of DPI formulations of protein and peptide drugs using advanced spray drying. An overview of the challenges in maintaining protein stability during the drying process and stabilizing excipients used in spray drying of proteins and peptide drugs is discussed. Finally, a summary of spray-dried DPI formulations of protein and peptide drugs, their characterization, various DPI devices used to deliver protein and peptide drugs, and current clinical status are discussed.

Byline: M. Jimenez (1,2), H. S. Garcia (1), C. I. Beristain (2) Keywords: Oxidative stability; Whey protein; Encapsulation; Conjugated linoleic acid Abstract: Conjugated linoleic acid (CLA) as the free acid was microencapsulated using whey protein concentrate (WPC) as a wall material. An emulsion of CLA was prepared using an emulsifier formulated with a 1:4 (w/w) ratio of a 30% WPC solution and was spray-dried with a laboratory unit. Microcapsules were stored at 35 and 45 degC at different water activities. Oxidation was monitored by measuring the CLA concentration, and peroxide, anisidine and total oxidation values. The encapsulation efficiency was 89.60% with a surface oil concentration of 1.77 g/100 g of sample. Microcapsules stored at a.sub.w=0.743--0.898 had very good stability against oxidation for at least 60 days therefore WPC is considered as an effective microencapsulating agent. Author Affiliation: (1) Instituto Tecnologico de Veracruz, Miguel A. de Quevedo No. 2779, 91897, Veracruz, Ver., Mexico (2) Instituto de Ciencias Basicas, Universidad Veracruzana, Apdo. Postal 575, Rafael Sanchez Altamirano, Industrial-Animas, 91000, Xalapa Veracruz, Mexico Article History: Registration Date: 20/07/2004 Received Date: 22/03/2004 Online Date: 12/10/2004

The human immunodeficiency virus (HIV) impacts up to 37 million people globally, of which 1.8 million are children. To date, there is no cure for HIV, although treatment options such as antiretroviral therapy (ART) are available. ART, which involves a patient taking a combination of antiretrovirals, is being used to treat HIV clinically. Despite the effectiveness of ART, there is currently no palatable pediatric formulation to treat HIV in children, which has hindered patient compliance and overall treatment efficacy. In addition, anti-HIV therapeutics are often poorly water-soluble, and hence have poor bioavailability. In the present study, we developed a pediatric-friendly formulation for anti-HIV therapeutics with improved dissolution characteristics of the therapeutic agents. Lopinavir (LPV) and ritonavir (RTV), available as FDA-approved fixed-dose combination products, were chosen as model ART drugs, and the formulation and processing parameters of spray-dried cyclodextrin (CD)-based LPV and RTV complexes were studied. Results showed that the spray-dried complexes exhibited enhanced dissolution profiles in comparison to pure drugs, particularly spray-dried β-CD complexes, which showed the most favorable dissolution profiles. This current formulation with enhanced dissolution and taste-masking ability through the use of cyclodextrin has the potential to address the unmet need for the development of suitable pediatric formulations.

Cocrystals have gained a lot of consideration regarding its superior role in enhancement of solubility and dissolution of the included API. Cocrystals could be converted to coamorphous systems via different techniques like milling and quench cooling; however, the use of spray-drying technique has not been investigated before. So, the aim of this study was to explore the effect of spray drying on the amorphization of indomethacin/nicotinamide, INDNIC, as model cocrystals. Spray-drying operating parameters were optimized using the Taguchi design of experiment for maximum powder yield and low moisture content. The obtained INDNIC spray-dried cocrystals were characterized for their degree of crystallinity, morphology, moisture content, and dissolution performance. In addition, stability study was performed at different temperature and humidity conditions. Experimental design results delineate that spray-drying inlet temperature and cocrystal concentrations as the most influential factors for maximum powder yield and low moisture content. Powder X-ray diffraction and differential scanning calorimetry studies revealed the conversion of INDNIC cocrystals to a partial coamorphous or coamorphous structure without dissociation of INDNIC molecular structure. INDNIC coamorphous powders showed a significantly higher release of IND compared with cocrystals and remain physically stable for 2 months when stored in the refrigerator.

The purpose of this study was to develop and evaluate a new formulation of ziprasidone (ZIP) for improved fasted state absorption and sustained drug release. ZIP solid dispersions were produced via spray drying using Soluplus®, an amphiphilic polymer, as the solubility enhancer. Physicochemical analysis proved that ZIP presented at amorphous state in the spray-dried microparticles and the dissolution rate of ZIP from the Soluplus®-ZIP composite microparticles was significantly increased compared with that of the physical mixtures. Commonly used encapsulation materials including Eudragit® RL, Eudragit® S100 and Ethyl Cellulose were incorporated into the solid dispersions to regulate the drug release kinetics. The formulation containing ethyl cellulose provided the most sustained release behaviors. Pharmacokinetic studies in beagle dogs confirmed that there was no significant difference in oral bioavailability of the microparticles under fasted and fed states, and a prolonged T max value was simultaneously achieved compared with the commercial ZIP capsules.

Spray drying is an efficient technique that is used not only for rapid evaporation of the solvent from different systems but also for designing ultra-fine particles with various desirable characteristics. The obtained powders demonstrate reasonably narrow size distribution with a submicron-to-micron size range. It is one of the recent techniques applied to present acceptable solutions to enhance the absorption and bioavailability of some challenging drugs. In view of that, the purpose of this review is to shed some light on the wide variety of the recently developed fine particulate products that can be produced from spray-drying technique. This article reports the most outstanding advantages and challenges that could be overcome by exploiting the spray-drying technique for the production of different pharmaceuticals, including pure drug particles and drug-loaded polymeric carriers. The potential of this technique, whether used alone or in combination with other methods, in order to develop reproducible and scalable procedures for the best translation of bench-to-bedside innovation of pharmaceutical products is hereby discussed.

The addition of matrix formers within a formulation provides a means for enhancing the redispersibility of nanoparticles (NPs) enabling them to retain their advantageous properties imparted onto them by their sub-micron size. In this work, NPs were isolated in the solid state via spray drying with a range of sugars. The processed powders were characterized, establishing that itraconazole (ITR) nanostructured microparticles (NMPs) spray dried in the presence of mannitol and trehalose had favorable redispersibility confirmed by dynamic light scattering and nanoparticle tracking analysis. Solid-state analysis confirmed the crystalline nature of NMPs based on mannitol and the amorphous character of trehalose-based NMPs. The NMPs powders were compacted at a range of pressures, producing tablets with high tensile strength without compromising their disintegration time. A greater amount of ITR was solubilized from trehalose NMPs compared to the mannitol-based compacts in 0.1 M HCl, showing a promise for enhanced in vivo activity. Overall, as trehalose exhibited superior carrier properties for ITR NMPs, this type of excipient included in the formulation warrants careful consideration. The structured approach to matrix former selection and tabletting studies can reduce the amount of material and time required for testing in the initial stages of product development.

Spherical-like MgO nanostructures have been synthesized efficiently via spray-drying combined with calcination using magnesium acetate as magnesium source. The products were characterized by means of X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and the specific surface areas were calculated using the Brunauer-Emmett-Teller (BET) method. The obtained spherical-like MgO nanostructures exhibit uniform pore sizes (7.7 nm) and high specific surface areas (180 m 2  g -1 ). The adsorption kinetics and isotherm data agree well with pseudo-second-order model and Langmuir model, indicating the monolayer chemisorption of heavy metal ions. The spherical-like MgO nanostructures exhibited high adsorption performance for Pb(II) and Cd(II) ions, and the maximum adsorption capacities were up to 5214 mg g -1 and 4187 mg g -1 , respectively. These values are much higher than those reported MgO-based adsorbents. Moreover, in less than 10 min, Pb(II) and Cd(II) ions in solution can be almost removed, which means that the spherical-like MgO possesses a high adsorption rate. XRD and FTIR analysis revealed the adsorption mechanism of Pb(II) and Cd(II) ions on MgO, which was mainly due to hydroxyl functional groups and ion exchange between Mg and heavy metal ions on the surface of MgO. These favorable performances recommend that the synthesized spherical-like MgO nanostructures would be a potential adsorbent for rapid removal of heavy metal ions from wastewater.

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.

Dry powder inhalers (DPIs) have been proposed as an alternative administration route for protein and peptide drugs. However, DPI particles are easy to aggregate due to the strong interactions between the particles, leading to poor aerosolization performance. In this study, fragmented particles containing octreotide acetate (OA) were prepared by spray drying technique for dry powder inhalation, which were expected to decrease the particle-particle interaction by reducing the contact sites. Mannitol and ammonium carbonate were used as protein stabilizer and fragment-forming agent, respectively. The obtained fragmented particles presented larger particle size, lower density, better dispersibility, and well in vitro aerodynamic behavior (emitted dose > 97%, fine particle fraction ≈ 40%). The circular dichroism spectrum results indicated that OA maintained the stability throughout the spray drying process. The relative bioavailability of dry powder inhalation (DPI) compared with subcutaneous injection of commercial product was up to 88.0%, demonstrating the feasibility of DPI for OA delivery. These results confirmed that the proposed fragmented particles had great potential for pulmonary delivery of protein and peptide drugs in a painless, rapid, and convenient manner.

Nanoscale tungsten (W) powder is used in some special materials. In this study, a hollow superstructure W powder consisting of nanoparticles was synthesized by spray drying combined with two-step calcination from commercial (NH 4 ) 6 W 7 O 24 ·6H 2 O. The high-pressure gas (HPG) was the significant factor in spray drying process, which affect the BET surface area and average particles size of the spray-dried powders. The detailed influences of calcined steps and calcination temperature in the microstructure and average particles size of final W particles were investigated. The size distribution of as-synthesized nanoscale W particles with hollow superstructure was from 40 to 200 nm, and the average size was about 100 nm. The as-synthesized W powder shows good sintering properties. It should be noted that the powder technology in this study can be used to synthesize other powders with high-performance requirements. .

Microbial inoculant preparation is a prerequisite for its application in large-scale bioremediation. In the present study, Sphingomonas sp. DC-6, an efficient acetochlor-degrading strain, was used to investigate the process of preparing the inoculant. Optimization of submerged fermentation (SmF) by response surface methodology (RSM) resulted in a first 22% increase in biomass of liquid inoculant. Then, a biomass increase of 2.18 times with 14.58% shortened incubation period was further obtained in optimized medium using a 7.5-l bioreactor. However, less than 0.4% viable cells in liquid inoculant survived after 180-days storage. Thus, optimized spray drying conditions were subsequently employed for the production of high viability powder (2.11 × 10 12  cfu g - 1 powder) without additive and its survival ratio (SR) after 180-days storage was still maintained at 90.5%. Both the 180-days stored powder and the original powder showed the same degradation performance, being able to completely degrade 200 mg l - 1 acetochlor within 48 h. This study demonstrated that strain DC-6 was suitable for industrial production of bacteria powder and provided a potential approach for the preparation of pesticide-degrading microbial inoculant., Competing Interests: Compliance with ethical standardsOn behalf of all authors, the corresponding author states that there is no conflict of interest.

Spray drying is appropriate for the preservation of halophilic microorganisms due to the nature of these microorganisms, as they survive in adverse environmental conditions by being encapsulated in salt crystals. Artificial neural networks were in this study used to optimize practically significant spray-drying regimes of the C 50 -carotenoids producer Halobacterium salinarum. Immediately after drying, the samples contained up to 54% halobacterial biomass and less than 5% moisture, and the level of preservation of carotenoids was 95-97%. The storage of biomass at 4 °C resulted in the gradual degradation of the carotenoids, which reached 58-64% in the best samples after 1 year. A comprehensive study of changes in halobacteria biomass after spray drying and the nature of the damage provided new data on the survival and preservation of cells and biologically active substances in the various spray-drying regimes and at different storage times.

Many commonly used tablet fillers are not suitable for direct compaction process due to insufficient properties, mainly of flowability and compactability. This work therefore aimed to use co-spray drying with HPMC as a platform to improve direct compaction properties of various tablet fillers. Starch, calcium hydrogen phosphate dihydrate (DCPD), and mannitol were chosen as a representative of three types of commonly used fillers (i.e. organic macromolecules, water-insoluble inorganic salts, and water-soluble small molecular carbohydrates), respectively. The five-level central composite design-response surface methodology was used (i) to investigate the effects of HPMC level and solid content of the feed on various powder, tableting, and tablet properties of composite excipients, and (ii) to optimize the composition. The results showed that the impacts of the two factors on various properties of composite excipients showed great similarity, despite of significantly different primary properties of the parent fillers, and the HPMC level was the main contributor to the majority of the impacts. An increase in HPMC level significantly improved tablet tensile strength and various tableting parameters. For all the three fillers, their optimized composite excipients provided by the established models showed excellent performances as predicted. The platform suggested is confirmed to be effective and promising.

The present investigation was carried out to develop and characterize a multifunctional co-processed excipient for improving the compressibility of poorly compressible drugs. Etodolac was used as a model drug. Microcrystalline cellulose (MCC), lactose monohydrate (lactose), and StarCap 1500 (StarCap) were selected as components of the co-processed excipient. The spray drying method was used for co-processing of excipients. D-optimal mixture design was applied to optimize the proportion of component excipients. Statistical analysis of the D-optimal mixture design revealed that all response variables were significantly affected by the independent variables (p value < 0.05). Optimized composition was obtained from the desirability function. The optimized composition of the co-processed excipient was found to be 30% MCC, 25% lactose, and 45% StarCap. This optimized batch was evaluated for flow properties, compressibility parameters such as Kawakita's and Kuno's equation and Heckel's equation, and dilution potential. Evaluation parameters for flow properties (angle of repose, Carr's index, and Hausner's ratio) suggested excellent flow character. The parameters of Kawakita's and Kuno's equation and Heckel's equation suggested improvement in the compressibility of the model drug. Dilution potential was found to be 40%, and based on that, tablets of the model drug were formulated and evaluated for general evaluation parameters of tablets. All the parameters were found to be within the acceptance criteria which concluded that the multifunctional directly compressible co-processed excipient was prepared successfully that improved the compressibility of the poorly compressible model drug etodolac along with spray drying as an efficient method for the preparation of co-processed excipient.

The purpose of this study was to develop a combination method of wet milling and spray-drying technologies to prepare the solid dispersion and improve the dissolution rate of poorly water-soluble drug candidates. Azilsartan (AZL) was selected as the model drug for its poor water solubility. In the study, AZL-loaded solid dispersion was prepared with polyethylene glycol 6000 (PEG6000) and hydroxypropyl cellulose with super low viscosity (HPC-SL) as stabilizers by using combination of wet grinding and spray-drying methods. The high AZL loading solid dispersion was then characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Besides, dissolution test was carried out by the paddle method and stability investigation was also conducted. As a result, the dissolution rate of the solid dispersion tablets was found to be greater than conventional tablets, but in close agreement with market tablets. Furthermore, the formulation was shown to be stable at 40 ± 2°C and 75 ± 5% for at least 6 months, owing to its decreased particle size, morphology, and its crystal form. It was concluded that the combination of wet milling and spray-drying approaches to prepare solid dispersion would be a prospective method to improve the dissolution rate of poorly water-soluble drugs.

Spray-drying (SD) is widely considered a suitable method to preserve microorganisms, but data regarding yeasts are still scanty. In this study, the effect of growing media, process variables and carriers over viability of a wild wine Saccharomyces (S.) cerevisiae LM52 was evaluated. For biomass production, the strain was grown (batch and fed-batch fermentation) in a synthetic, as well as in a beet sugar molasses based-medium. Drying of cells resuspended in several combinations of soluble starch and maltose was performed at different inlet and outlet temperatures. Under the best conditions-suspension in soluble starch plus maltose couplet to inlet and outlet temperatures of 110 and 55 °C, respectively-the loss of viability of S. cerevisiae LM52 was 0.8 ± 0.1 and 0.5 ± 0.2 Log c.f.u. g(-1) for synthetic and molasses-based medium, respectively. Similar results were obtained when S. cerevisiae strains Zymoflore F15 and EC1118, isolated from commercial active dry yeast (ADY), were tested. Moreover, powders retained a high vitality and showed good fermentation performances up to 6 month of storage, at both 4 and -20 °C. Finally, fermentation performances of different kinds of dried formulates (SD and ADY) compared with fresh cultures did not show significant differences. The procedure proposed allowed a small-scale production of yeast in continuous operation with relatively simple equipment, and may thus represent a rapid response-on-demand for the production of autochthonous yeasts for local wine-making.

Plant growth promoting bacteria and nitrogen-fixing bacteria (NFB) used for crop inoculation have important biotechnological potential as a sustainable fertilization tool. However, the main limitation of this technology is the low inoculum survival rate under field conditions. Microencapsulation of bacterial cells in polymer matrices provides a controlled release and greater protection against environmental conditions. In this context, the aim of this study was to isolate and characterize putative NFB associated with lupin nodules and to evaluate their microencapsulation by spray drying. For this purpose, 21 putative NFB were isolated from lupin nodules and characterized (16S rRNA genes). Microencapsulation of bacterial cells by spray drying was studied using a mixture of sodium alginate:maltodextrin at different ratios (0:15, 1:14, 2:13) and concentrations (15 and 30% solids) as the wall material. The microcapsules were observed under scanning electron microscopy to verify their suitable morphology. Results showed the association between lupin nodules of diverse known NFB and nodule-forming bacteria belonging to Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Bacteroidetes. In microencapsulation assays, the 1:14 ratio of sodium alginate:maltodextrin (15% solids) showed the highest cell survival rate (79%), with a microcapsule yield of 27% and spherical microcapsules of 5-50 µm in diameter. In conclusion, diverse putative NFB genera and nodule-forming bacteria are associated with the nodules of lupine plants grown in soils in southern Chile, and their microencapsulation by spray drying using sodium alginate:maltodextrin represents a scalable process to generate a biofertilizer as an alternative to traditional nitrogen fertilization.

The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC>THF-URE>THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.

Moisture content and aerodynamic particle size are critical quality attributes for spray-dried protein formulations. In this study, spray-dried insulin powders intended for pulmonary delivery were produced applying design of experiments methodology. Near infrared spectroscopy (NIR) in combination with preprocessing and multivariate analysis in the form of partial least squares projections to latent structures (PLS) were used to correlate the spectral data with moisture content and aerodynamic particle size measured by a time of flight principle. PLS models predicting the moisture content were based on the chemical information of the water molecules in the NIR spectrum. Models yielded prediction errors (RMSEP) between 0.39% and 0.48% with thermal gravimetric analysis used as reference method. The PLS models predicting the aerodynamic particle size were based on baseline offset in the NIR spectra and yielded prediction errors between 0.27 and 0.48 μm. The morphology of the spray-dried particles had a significant impact on the predictive ability of the models. Good predictive models could be obtained for spherical particles with a calibration error (RMSECV) of 0.22 μm, whereas wrinkled particles resulted in much less robust models with a Q (2) of 0.69. Based on the results in this study, NIR is a suitable tool for process analysis of the spray-drying process and for control of moisture content and particle size, in particular for smooth and spherical particles.

Due to the fact that the number of new poorly soluble active pharmaceutical ingredients is increasing, it is important to investigate the possibilities of improvement of their solubility in order to obtain a final pharmaceutical formulation with enhanced bioavailability. One of the strategies to increase drug solubility is the inclusion of the APIs in cyclodextrins. The aim of this study was to investigate the possibility of aripiprazole solubility improvement by inclusion in (2-hydroxy)propyl-β-cyclodextrin (HPBCD) and simultaneous manipulation of pH of the medium and addition of polyvinylpyrrolidone. Aripiprazole-HPBCD complexes were prepared by spray drying aqueous drug-HPBCD solutions, and their properties were compared with those prepared by solvent-drop co-grinding and physical mixing. The obtained powders were characterized by thermoanalytical methods (TGA and DSC), FTIR spectroscopy, their dissolution properties were assessed, while the binding of aripiprazole into the cavity of HPBCD was studied by molecular docking simulations. The solubilization capacity was found to be dependent on pH as well as the buffer solution's ionic composition. The presence of PVP in the formulation could affect the solubilization capacity significantly, but further experimentation is required before its effect is fully understood. On the basis of solubility studies, the drug/HPBCD stoichiometry was found to be 1:3. The spray-dried products were free of crystalline aripiprazole, they possessed higher solubility and dissolution rate, and were stable enough over a prolonged period of storage. Spray drying of cyclodextrin solutions proved to be an appropriate and efficient technique for the preparation of highly soluble inclusion compounds of aripiprazole and HPBCD.

Solid-state characterisation of a drug following pharmaceutical processing and upon storage is fundamental to successful dosage form development. The aim of the study was to investigate the effects of using different solvents, feed concentrations and spray drier configuration on the solid-state nature of the highly polymorphic model drug, sulfathiazole (ST) and its sodium salt (STNa). The drugs were spray-dried from ethanol, acetone and mixtures of these organic solvents with water. Additionally, STNa was spray-dried from pure water. The physicochemical properties including the physical stability of the spray-dried powders were compared to the unprocessed materials. Spray drying of ST from either acetonic or ethanolic solutions with the spray drier operating in a closed cycle mode yielded crystalline powders. In contrast, the powders obtained from ethanolic solutions with the spray drier operating in an open cycle mode were amorphous. Amorphous ST crystallised to pure form I at ≤35 % relative humidity (RH) or to polymorphic mixtures at higher RH values. The usual crystal habit of form I is needle-like, but spherical particles of this polymorph were generated by spray drying. STNa solutions resulted in an amorphous material upon processing, regardless of the solvent and the spray drier configuration employed. Moisture induced crystallisation of amorphous STNa to a sesquihydrate, whilst crystallisation upon heating gave rise to a new anhydrous polymorph. This study indicated that control of processing and storage parameters can be exploited to produce drugs with a specific/desired solid-state nature.

The main objective of this study was to evaluate the stability of astaxanthin after drying and storage at different conditions during a 9-week period. Recovery of astaxanthin was evaluated by extracting pigments from the dried powders and analysing extracts by HPLC. The powders obtained were stored under different conditions of temperature and oxygen level and the effects on the degradation of astaxanthin were examined. Under the experimental conditions conducted in this study, the drying temperature that yielded the highest content of astaxanthin was 220°C, as the inlet, and 120°C, as the outlet temperature of the drying chamber. The best results were obtained for biomass dried at 180/110°C and stored at -21°C under nitrogen, with astaxanthin degradation lower than 10% after 9 weeks of storage. A reasonable preservation of astaxanthin can be achieved by conditions 180/80°C, -21°C nitrogen, 180/110°C, 21°C nitrogen, and 220/80°C, 21°C vacuum: the ratio of astaxanthin degradation is equal or inferior to 40%. In order to prevent astaxanthin degradation of Haematococcus pluvialis biomass, it is recommended the storage of the spray dried carotenized cells (180/110ºC) under nitrogen and -21°C.

The effects of spray-drying process and acidic solvent system on physicochemical properties of chitosan salts were investigated. Chitosan used in spray dryings was obtained by deacetylation of chitin from lobster (Panulirus argus) origin. The chitosan acid salts were prepared in a laboratory-scale spray drier, and organic acetic acid, lactic acid, and citric acid were used as solvents in the process. The physicochemical properties of chitosan salts were investigated by means of solid-state CP-MAS (13)C nuclear magnetic resonance (NMR), X-ray powder diffraction (XRPD), differential scanning calorimetry, and Fourier transform infrared spectrometry (FTIR) and near-infrared spectroscopy. The morphology of spray-dried chitosan acid salts showed tendency toward higher sphericity when higher temperatures in a spray-drying process were applied. Analysis by XRPD indicated that all chitosan acid salts studied were amorphous solids. Solid-state (13)C NMR spectra revealed the evidence of the partial conversion of chitosan acetate to chitin and also conversion to acetyl amide form which appears to be dependent on the spray-drying process. The FTIR spectra suggested that the organic acids applied in spray drying may interact with chitosan at the position of amino groups to form chitosan salts. With all three chitosan acid salts, the FTIR bands at 1,597 and 1,615 cm(-1) were diminished suggesting that -NH groups are protonated. The FTIR spectra of all chitosan acid salts exhibited ammonium and carboxylate bands at 1,630 and 1,556 cm(-1), respectively. In conclusion, spray drying is a potential method of preparing acid salts from chitosan obtained by deacetylation of chitin from lobster (P. argus) origin.

This article describes the preparation of starch particles, by spray drying, for possible application to a dry powder coating process. Dry powder coating consists of spraying a fine powder and a plasticizer on particles. The efficiency of the coating is linked to the powder morphological and dimensional characteristics. Different experimental parameters of the spray-drying process were analyzed, including type of solvent, starch concentration, rate of polymer feeding, pressure of the atomizing air, drying air flow, and temperature of drying air. An optimization and screening of the experimental parameters by a design of the experiment (DOE) approach have been done. Finally, the produced spray-dried starch particles were conveniently tested in a dry coating process, in comparison to the commercial initial starch. The obtained results, in terms of coating efficiency, demonstrated that the spray-dried particles led to a sharp increase of coating efficiency value.

Solid amorphous dispersions are frequently used to improve the solubility and, thus, the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Spray-drying, a well-characterized pharmaceutical unit operation, is ideally suited to producing solid amorphous dispersions due to its rapid drying kinetics. This paper describes a novel flowchart methodology based on fundamental engineering models and state-of-the-art process characterization techniques that ensure that spray-drying process development and scale-up are efficient and require minimal time and API. This methodology offers substantive advantages over traditional process-development methods, which are often empirical and require large quantities of API and long development times. This approach is also in alignment with the current guidance on Pharmaceutical Development Q8(R1). The methodology is used from early formulation-screening activities (involving milligrams of API) through process development and scale-up for early clinical supplies (involving kilograms of API) to commercial manufacturing (involving metric tons of API). It has been used to progress numerous spray-dried dispersion formulations, increasing bioavailability of formulations at preclinical through commercial scales.