Isolation and Physical Property Optimization of an Amorphous Drug Substance Utilizing a High Surface Area Magnesium Aluminometasilicate (Neusilin(®) US2).

Control and optimization of the physical properties of a drug substance (DS) are critical to the development of robust drug product manufacturing processes and performance. A lack of isolatable, for example, crystalline, DS solid forms can present challenges to achieving this control. In this study, an isolation scheme for an amorphous DS was developed and integrated into the synthetic route producing DS with optimized properties. An inert absorbent excipient (Neusilin® US2) was used to isolate the DS via a novel antisolvent scheme as the final step of the route. Isolation was executed at kilogram scale utilizing conventional equipment. The resulting 50 wt% DS:Neusilin complex had improved physical stability and exceptional micromeritic and tableting properties. Improved dissolution was observed and attributed to enhanced dispersion and increased surface area. Characterization data suggest a high degree of penetration of the DS into the Neusilin, with DS occupying 70% of mesopore and 12% of macropore volume. This approach has application in the isolation and particle engineering of difficult to isolate DS without additional unit operation, such as spray drying, and has the potential for a high degree of optimization and control of physical properties over the course of DS development.

Struvite recovery from anaerobically digested dairy manure: A review of application potential and hindrances.

Anaerobically digested dairy manure is rich in ammonium, orthophosphates, and magnesium, indicating a high potential for struvite recovery. Continuous generation of large amounts of dairy manure plus increasing global interest in anaerobic digestion of dairy manure suggest a huge market for struvite production with anaerobically digested dairy manure. However, the complex chemical composition of digested dairy manure presents hindrances to struvite recovery. This review paper assesses the significance and potential of struvite recovery from anaerobically digested dairy manure, identifies the factors hindering struvite recovery, and discusses the methods to overcome hindrances and the measures to improve phosphorus speciation of dairy manure for struvite formation. This paper proposes using "struvite recovery potential" or Pstruvite based on the least molar activity of struvite component ions in addition to "supersaturation ratio" to identify the potential for struvite recovery. The probable hindrances mainly include high Ca(2+) concentration and molar activity ratios of Ca(2+): Mg(2+) and Ca(2+): PO4(3-), high ionic strength, and high alkalinity. Struvite formation and purity is likely a function of all the interfering variables, rather than just a single factor with digested dairy manure. Potential enhancement measures need to be tested for technical and economic feasibility and applicability to various sources of digested dairy manure. This review paper provides guidance to overcoming the hindrances of digested dairy manure to struvite formation.

Efficient magnesium lactate production with in situ product removal by crystallization.

In this paper, attempts were made to develop an in situ product removal process for magnesium lactate production based on crystallization. The crystallization was conducted at 42°C without seed crystal addition. The product concentration, productivity and yield of fermentation coupled with in situ product removal (ISPR) reached 143 g L(-1), 2.41 g L(-1)h(-1) and 94.3%. In four cycles of crystallization, the average reuse rate of fermentation medium and removal rate of product reached 64.0% and 77.7%. At the same time, ISPR fermentation saved 40% water, 41% inorganic salts and 43% yeast extract (YE) as compared to fed-batch fermentation. The process introduces an effective way to reduce the amount of waste water and the raw material cost in magnesium lactate fermentation.

Effect of magnesium dose on amount of pharmaceuticals in struvite recovered from urine.

Phosphorus (P) recovery was carried out through struvite precipitation from urines. Human urine, however, contains not only high nutrients for plants, such as P and nitrogen, but also pharmaceuticals and hormones. In this work, effects of magnesium (Mg) dose (in terms of Mg:P ratio) on P recovery efficiency and pharmaceutical amounts contained in struvite were investigated. Batch-scale experiments of synthetic and human urines revealed that struvite precipitation formed more X-shaped crystals with an increased molar ratio of Mg:P, while the amount of pharmaceuticals (tetracycline, demeclocycline, and oxytetracycline) in struvite decreased with an increased molar ratio of Mg:P. The lowest pharmaceutical amounts in struvite were found at the Mg:P ratio of 2:1 from both samples. Moreover, the maximum P recovery efficiency, quantity and purity of struvite were found in the range of 1.21 to 2:1. It indicated that the molar ratio of Mg:P has a significant impact on struvite precipitation in terms of pharmaceutical amounts in struvite; morphology, quantity and purity of struvite; and P recovery.

Effect of humic substances on phosphorus removal by struvite precipitation.

Humic substances (HS) are a major fraction of dissolved organic matters in wastewater. The effect of HS on phosphorus removal by struvite precipitation was investigated using synthetic wastewater under different initial pH values, Mg/P molar ratios and HS concentrations. The composition, morphology and thermal properties of harvested precipitates were analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM) and thermo-gravimetric analysis (TGA), respectively. It showed that inhibition effect of HS reached its maximum value of 48.9% at pH 8.0, and decreased to below 10% at pH>9.0. The increase of Mg/P ratio enhanced phosphorus removal efficiency, and thus reduced the influence of HS on struvite precipitation. At pH 9.0, the inhibitory effect of initial HS concentration matched the modified Monod model with half maximum inhibition concentration of 356mgL(-1), and 29% HS was removed in conjunction with struvite crystallisation. XRD analysis revealed that the crystal form of struvite precipitates was changed in the presence of HS. The morphology of harvested struvite was transformed from prismatic to pyramid owing to the coprecipitation of HS on crystal surface. TGA results revealed that the presence of HS could compromise struvite purity.

A new algorithm for design, operation and cost assessment of struvite (MgNH4PO4) precipitation processes.

Deliberate struvite (MgNH4PO4) precipitation from wastewater streams has been the topic of extensive research in the last two decades and is expected to gather worldwide momentum in the near future as a P-reuse technique. A wide range of operational alternatives has been reported for struvite precipitation, including the application of various Mg(II) sources, two pH elevation techniques and several Mg:P ratios and pH values. The choice of each operational parameter within the struvite precipitation process affects process efficiency, the overall cost and also the choice of other operational parameters. Thus, a comprehensive simulation program that takes all these parameters into account is essential for process design. This paper introduces a systematic decision-supporting tool which accepts a wide range of possible operational parameters, including unconventional Mg(II) sources (i.e. seawater and seawater nanofiltration brines). The study is supplied with a free-of-charge computerized tool (http://tx.technion.ac.il/~agrengn/agr/Struvite_Program.zip) which links two computer platforms (Python and PHREEQC) for executing thermodynamic calculations according to predefined kinetic considerations. The model can be (inter alia) used for optimizing the struvite-fluidized bed reactor process operation with respect to P removal efficiency, struvite purity and economic feasibility of the chosen alternative. The paper describes the algorithm and its underlying assumptions, and shows results (i.e. effluent water quality, cost breakdown and P removal efficiency) of several case studies consisting of typical wastewaters treated at various operational conditions.

Membrane-integrated physico-chemical treatment of coke-oven wastewater: transport modelling and economic evaluation.

A modelling and simulation study with economic evaluation was carried out for an advanced membrane-integrated hybrid treatment process that ensures reuse of water with recovery of ammoniacal nitrogen as struvite from coke-oven wastewater. Linearized transport model was developed based on extended Nernst-Plank and concentration polarization modulus equation. Effects of pH, transmembrane pressure and cross-flow rate of interest on membrane charge density, solute rejection and solvent flux were investigated. The membrane module was successful in yielding a pure water flux as high as 120 L m(-2) h(-1) removing more than 95 and 96% of the cyanide and phenol, respectively, while permeating more than 90% NH4 (+)-N at a transmembrane pressure of only 15 × 10(2) KPa and at a pH of 10 for a volumetric cross-flow rate of 800 L h(-1). The Fenton's reagents were used to degrade more than 99% of pollutants present in the concentrated stream. The developed model could successfully predict the plant performance as reflected in the very low relative error (0.01-0.12) and overall high correlation coefficient (R(2) > 0.96). Economic analysis indicated that such a membrane-integrated hybrid system could be quite promising in coke wastewater treatment at low cost i.e. $0.934/m(2) of wastewater.

Enhanced struvite recovery from wastewater using a novel cone-inserted fluidized bed reactor.

The feasibility of struvite recovery at low (12.5 mg/L) and high (120 mg/L) phosphorus concentrations was studied by constructing a novel fluidized bed reactor with cones (FBRwc) and without cones (FBRwoc). The crystallization process was continuously operated for 133 days under different hydraulic retention times (HRT = 1-10 hr), pH (7.5-10), and molar ratios of Mg/P (0.75-1.75), N/P (1-10) and Ca/Mg (0-2). The optimum operating conditions of HRT, pH, Mg/P and N/P molar ratios were found to be 2 hr, 9, 1.25, and 7.5, respectively. Under these optimum conditions, the phosphorus precipitation efficiencies of FBRwc were 93% for low and 98% for high phosphorus influent; however, the efficiencies were 78% and 81% for FBRwoc, respectively. Due to crystal losses at each junction (17%-31%), the crystal recovery efficiency of FBRwoc was relatively low (47%-65%) for both influent concentrations. However, the losses were minimal in FBRwc, which showed 75% and 92% crystal recovery for low and high phosphorus concentrations, respectively. At low calcium concentration, crystal chemical analysis showed the product to be pure struvite (> 99%). The scanning electron microscope and X-ray diffraction results further confirmed that the crystal recovered from FBRwc contained pure struvite, which could be considered a high quality fertilizer. Except HRT, all parameters (pH, Mg/P, N/P and Ca/Mg) were found to be influencing factors for FBRwc performance. Overall, inserting cones in each part of the reactor played a significant role in enhancing struvite recovery from a wide range of phosphorus-containing wastewater.

Recovery of struvite via coagulation and flocculation using natural compounds.

One of the major setbacks of struvite recovery processes is the difficulty in harvesting struvite crystals. This study evaluates the use of different coagulants to improve precipitation of struvite (MgNH4PO4.6H20) crystals. Chitosan and poly(diallyldimethyl ammonium chloride) (Poly-DADMAC) as a coagulant-flocculent and alginate and bentonite as a coagulant aid have been examined in jar tests. Also, a continuous three-phase process, i.e., struvite crystallization, coagulation/flocculation and precipitation process, was set up for real wastewater. Addition of chitosan as the coagulant and bentonite as the coagulant aid was significantly more efficient in forming struvite flocs in comparison to Poly-DADMAC alone or with coagulant aid, which did not show any positive effect. The calculated average settling velocity of struvite with chitosan-bentonite addition in synthetic and in real wastewater increased by approximately 5.3 and 2.8 folds, respectively, compared with that of no coagulant/flocculent addition. Phosphorus recovery of over 70% was achieved by the continuous process. Findings in this study clearly confirmed the possibility of using chitosan and bentonite as an efficient coagulant-flocculent to enhance the recovery of struvite crystals.

Electrochemical struvite precipitation from digestate with a fluidized bed cathode microbial electrolysis cell.

Microbial electrolysis cells (MECs) can be used to simultaneously convert wastewater organics to hydrogen and precipitate struvite, but scale formation at the cathode surface can block catalytic active sites and limit extended operation. To promote bulk phase struvite precipitation and minimize cathode scaling, a two-chamber MEC was designed with a fluidized bed to produce suspended particles and inhibit scale formation on the cathode surface. MEC operation elevated the cathode pH to between 8.3 and 8.7 under continuous flow conditions. Soluble phosphorus removal using digester effluent ranged from 70 to 85% with current generation, compared to 10-20% for the control (open circuit conditions). At low current densities (≤2 mA/m(2)), scouring of the cathode by fluidized particles prevented scale accumulation over a period of 8 days. There was nearly identical removal of soluble phosphorus and magnesium from solution, and an equimolar composition in the collected solids, supporting phosphorus removal by struvite formation. At an applied voltage of 1.0 V, energy consumption from the power supply and pumping (0.2 Wh/L, 7.5 Wh/g-P) was significantly less than that needed by other struvite formation methods based on pH adjustment such as aeration and NaOH addition. In the anode chamber, current generation led to COD oxidation (1.1-2.1 g-COD/L-d) and ammonium removal (7-12 mM) from digestate amended with 1 g/L of sodium acetate. These results indicate that a fluidized bed cathode MEC is a promising method of sustainable electrochemical nutrient and energy recovery method for nutrient rich wastewaters.

Modeling phosphorus removal and recovery from anaerobic digester supernatant through struvite crystallization in a fluidized bed reactor.

The cost associated with the disposal of phosphate-rich sludge, the stringent regulations to limit phosphate discharge into aquatic environments, and resource shortages resulting from limited phosphorus rock reserves, have diverted attention to phosphorus recovery in the form of struvite (MAP: MgNH4PO4·6H2O) crystals, which can essentially be used as a slow release fertilizer. Fluidized-bed crystallization is one of the most efficient unit processes used in struvite crystallization from wastewater. In this study, a comprehensive mathematical model, incorporating solution thermodynamics, struvite precipitation kinetics and reactor hydrodynamics, was developed to illustrate phosphorus depletion through struvite crystal growth in a continuous, fluidized-bed crystallizer. A thermodynamic equilibrium model for struvite precipitation was linked to the fluidized-bed reactor model. While the equilibrium model provided information on supersaturation generation, the reactor model captured the dynamic behavior of the crystal growth processes, as well as the effect of the reactor hydrodynamics on the overall process performance. The model was then used for performance evaluation of the reactor, in terms of removal efficiencies of struvite constituent species (Mg, NH4 and PO4), and the average product crystal sizes. The model also determined the variation of species concentration of struvite within the crystal bed height. The species concentrations at two extreme ends (inlet and outlet) were used to evaluate the reactor performance. The model predictions provided a reasonably good fit with the experimental results for PO4-P, NH4-N and Mg removals. Predicated average crystal sizes also matched fairly well with the experimental observations. Therefore, this model can be used as a tool for performance evaluation and process optimization of struvite crystallization in a fluidized-bed reactor.

Redox tuning and species distribution in Maya Blue-type materials: a reassessment.

Maya Blue-type specimens prepared from indigo (1 wt %) plus kaolinite, montmorillonite, palygorskite, sepiolite, and silicalite are studied. Liquid chromatography with diode array detection, ultra-performance liquid chromatography coupled with mass spectrometry, and pyrolysis-silylation gas chromatography-mass spectrometry analyses of the extracts from these specimens combined with spectral and solid-state voltammetry, electrochemical impedance spectroscopy, and scanning electrochemical microscopy techniques provide evidence for the presence of a significant amount of dehydroindigo and isatin accompanying indigo and other minority organic compounds in all samples. Solid-state electrochemistry data permits the estimatation of indigo loading in archeological Maya Blue, which is in the range of 0.2 to 1.5 wt %. These results support a view of 'genuine' Maya Blue-type materials as complex polyfunctional organic-inorganic hybrids.

Phosphates (V) recovery from phosphorus mineral fertilizers industry wastewater by continuous struvite reaction crystallization process.

Continuous DT MSMPR (Draft Tube Mixed Suspension Mixed Product Removal) crystallizer was provided with typical wastewater from phosphorus mineral fertilizers industry (pH < 4, 0.445 mass % of PO4(3-), inorganic impurities presence), dissolved substrates (magnesium and ammonium chlorides) and solution alkalising the environment of struvite MgNH4PO4·6H2O reaction crystallization process. Research ran in constant temperature 298 K assuming stoichiometric proportions of substrates or 20% excess of magnesium ions. Influence of pH (8.5-10) and mean residence time (900-3600 s) on product size distribution, its chemical composition, crystals shape, size-homogeneity and process kinetics was identified. Crystals of mean size ca. 25-37 µm and homogeneity CV 70-83% were produced. The largest crystals, of acceptable homogeneity, were produced using 20% excess of magnesium ions, pH 9 and mean residence time 3600 s. Under these conditions nucleation rate did not exceed 9 × 10(7) 1/(s m(3)) according to SIG (Size Independent Growth) MSMPR kinetic model. Linear crystal growth rate was 4.27 × 10(-9) m/s. Excess of magnesium ions influenced struvite reaction crystallization process yield advantageously. Concentration of phosphate(V) ions decreased from 0.445 to 9.2 × 10(-4) mass %. This can be regarded as a very good process result. In product crystals, besides main component - struvite, all impurities from wastewater were detected analytically.

Biologically and chemically mediated adsorption and precipitation of phosphorus from wastewater.

Biologically and chemically mediated adsorption and precipitation processes offer a range of approaches for removing phosphorus (P) from agricultural, domestic and industrial effluents. Technologies implemented at full-scale include filtration by adsorbent media, such as steel slag, and recovery of phosphorus as struvite, which has been successfully commercialised as a fertiliser. Other promising technologies under investigation include P removal by polymers and nanomaterials as well as struvite formation by bacteria. There is a need to focus future research on improving the efficiency of P removal by adsorption and precipitation. This can be achieved by techniques such as regenerating filters, polymers and nanomaterials for renewed P removal. Research is also needed to optimise the fertiliser potential of struvite precipitates.

Removal and recovery of phosphorus as struvite from swine wastewater using microbial fuel cell.

Air-cathode single chamber microbial fuel cells (MFCs) were operated with swine wastewater. The maximum power density, the maximum current density, the average value of COD-removal efficiency, and the coulombic efficiency were 1-2.3 W/m(2), 6.0-7.0 A/m(2), 76-91%, and 37-47%, respectively. During operation, 70-82% of the phosphorus was removed from the influent, and some precipitations were observed on the surface of the liquid side of the cathodes. The amount of phosphorus contained in these precipitates was estimated to be equivalent 4.6-27% of the influent. The main component of these precipitates was revealed by X-ray diffraction analysis to be struvite. Furthermore, our results indicate that phosphorus in suspended solid form was first dissolved, and then precipitated on the cathode. By scanning electron microscope observation, the morphology of the precipitates was irregularly shaped, including crystals with hexagonal cross-section surfaces, and was different from the familiar needle-like ones. These results indicate that simultaneous recovery of electrical power and phosphorus from wastewater by microbial fuel cell is possible.

Overcoming challenges to struvite recovery from anaerobically digested dairy manure.

Recovering struvite from dairy manure has consistently posed problems for researchers. This study separated solids from anaerobically digested dairy manure using a filtration system. Filtrate was rich in free magnesium (160 to 423 mg/L), ammonium (320 to 1800 mg N/L) and orthophosphate (93 to 332 mg P/L). High concentrations of free calcium (128 to 361 mg/L) and alkalinity (3309 to 6567 mg/L as CaCO3), however, may hinder struvite precipitation. Batch precipitation tests were conducted to identify and overcome factors that interfere with struvite formation. Precipitation tests at pH 9 identified calcium and ionic strength as most probable interferences. Calcium addition did not significantly change phosphorus removal efficiency, but decreased struvite purity because of formation of calcium phosphates when Ca:P activity ratio was greater than 0.5 to 1. Batch tests demonstrated effective calcium removal from anaerobically digested dairy manure through precipitation of calcium carbonate at pH 9 to 10 while retaining magnesium and orthophosphate, lessening hindrance to struvite formation.

Phosphate recovery as struvite within a single chamber microbial electrolysis cell.

An energy efficient method of concurrent hydrogen gas and struvite (MgNH(4)PO(4)·6H(2)O) production was investigated based on bioelectrochemically driven struvite crystallization at the cathode of a single chamber microbial electrolysis struvite-precipitation cell (MESC). The MESC cathodes were either stainless steel 304 mesh or flat plates. Phosphate removal ranged from 20% to 40%, with higher removals obtained using mesh cathodes than with flat plates. Cathode accumulated crystals were verified as struvite using a scanning electron microscope capable of energy dispersive spectroscopy (SEM-EDS). Crystal accumulation did not affect the rate of hydrogen production in struvite reactors. The rate of struvite crystallization (g/m(2)-h) and hydrogen production (m(3)/m(3)-d) were shown to be dependent on applied voltage and cathode material. Overall energy efficiencies (substrate and electricity) were high (73 ± 4%) and not dependent on applied voltage. These results show that MESCs may be useful both as a method for hydrogen gas and struvite production.

The contribution of exopolysaccharides induced struvites accumulation to ammonium adsorption in aerobic granular sludge.

Aerobic granular sludge from a lab-scale reactor with simultaneous nitrification/denitrification and enhanced biological phosphorus removal processes exhibited significant amount of ammonium adsorption (1.5 mg NH4+-N/g TSS at an ammonium concentration of 30 mg N/L). Potassium release accompanied ammonium adsorption, indicating an ion exchange process. The existence of potassium magnesium phosphate (K-struvite) as one of potassium sources in the granular sludge was studied by X-ray diffraction analysis (XRD). Artificially prepared K-struvite was indeed shown to adsorb ammonium. Alginate-like exopolysaccharides were isolated and their inducement for struvite formation was investigated as well. Potassium magnesium phosphate proved to be a major factor for ammonium adsorption on the granular sludge. Struvites (potassium/ammonium magnesium phosphate) accumulate in aerobic granular sludge due to inducing of precipitation by alginate-like exopolysaccharides.

Recovery of phosphorus as struvite from sewage sludge ash.

Phosphorus (P) is an element vital for all living organisms, yet the world's reserves of phosphate rock are becoming depleted. This study investigated an effective P recovery method from sludge ash via struvite precipitation. Results showed that more than 95% of the total P content was extracted from sludge ash by applying 0.5 mol/L HCl at a liquid/solid ratio of 50 mL/g. Although heavy metal leaching also occurred during P extraction, cation exchange resin efficiently removed the heavy metals from the P-rich solution. Orthogonal tests showed that the optimal parameters for P precipitation as struvite would be a Mg:N:P molar ratio of 1.6:1.6:1 at pH 10.0. X-ray diffraction analysis validated the formation of struvite. Further investigations revealed that the harvested precipitate had a high struvite content (97%), high P bioavailability (94%), and low heavy metal content, which could be considered a high quality fertilizer.

Phosphorus removal from anaerobically digested swine wastewater through struvite precipitation.

Phosphorus removal from agricultural wastewater streams is an important aspect of managing surface water quality, due to the contribution of phosphorus to eutrophication. Removal of phosphorus through struvite precipitation allows for its recovery as a potential fertilizer, and by determining the best conditions for struvite precipitation the removal process can be optimized. The effects of pH, Mg:P ratio, and time on struvite precipitation from anaerobically digested swine manure effluent were investigated. Effluent with Mg:P ratios from 1.0:1 to 1.6:1 were adjusted to pH values between 7.5 and 9.5 and left to equilibrate for 24 h. Results indicate that phosphorus removal increased with increasing pH and Mg:P ratio; the maximum phosphorus removal achieved was 80% at pH 9.0 and a Mg:P ratio of 1.6:1. The purest struvite precipitate was found at pH 7.5, with calcium carbonate and struvite precipitating at higher pH values. A continuously stirred batch of centrate was adjusted to pH 8.4 to determine the struvite formation rate constant. The rate constant was found to be 1.55 h(-1), with 17% phosphorus removal during the first 20 min. The results indicate that struvite precipitation could be a viable method of phosphorus removal from anaerobically digested swine manure.