APPLICATION OF UF TECHNOLOGY TO LARGE-SCALE SYNTHESIS OF GT 267-004, A SEQUESTRANT FOR C. DIFFICILE TOXIN

GT 267-004 is a nonabsorbed, nonantibiotic, high molecular weight anionic polymer that is undergoing clinical evaluation as a Clostridium difficile toxin sequestrant. The API is a mixed salt form that consists of approximately 30 to 50% potassium and 70 to 50% sodium as the counterions on the polymer.

The initial polymerization process results in an aqueous polymer solution with the polymer in the 100% sodium form. It also contains some oligomeric impurities. UF technology was applied in a novel way to convert the single-salt polymer to the mixed salt form and to simultaneously remove the oligomers below the required specification limits in a single-unit operation.

Experiments with a UF lab unit validated the concept of simultaneously performing ion exchange and purification. An appropriate amount of potassium chloride was added to the polymer solution to carry out the ion exchange considering the selectivity of the polymer for the potassium ion over the sodium ion. The resulting mixed salts in solution were removed using ultrafiltration membranes. The process produced the API in excellent purity.

The lab data were used to scale up the process to produce several hundred kg of the API. The engineering analysis of the large-scale UF operation was carried out to run the UF process in the cyclic mode and in the diafiltration mode. The UF operation was optimized with respect to time, water usage, operability, and the concentration of product solution required for the subsequent processing.

The optimized UF process was found to be a very cost-effective and time-efficient route to produce the new API.     

INNOVATIVE APPROACHES TO SYNTHESIS OF GT 267-004, A SEQUESTRANT FOR C. DIFFICILE TOXIN

GT 267-004 is a nonabsorbed, nonantibiotic, high molecular weight anionic polymer that is undergoing clinical evaluation as a Clostridium difficile toxin sequestrant. The active pharmaceutical ingredient (API) is a mixed salt form that consists of approximately 30 to 50% potassium and 70 to 50% sodium as the counterions on the polymer. The initial polymerization process results in an aqueous polymer solution with the polymer in the 100% sodium form. This article describes the use of two innovative approaches, electrodialysis (ED) and ion exchange using ion exchange resins (IXR), to convert the single-salt polymer to the mixed-salt form. Electrodialysis experiments were conducted using a stack of five cells, each of which contained two cation and one anion exchange membranes. The electrodialysis was run in batch mode with a sodium chloride solution as the concentrate stream and a potassium chloride solution as the diluate stream. The ED process was monitored on-line by measuring the conductivity of the streams. Yield loss of the API through the ED membranes was minimal. The ED process was found to be fast, efficient, and reproducible. The ion exchange experiments were conducted using a strong acid cation resin in the potassium form. By using a fixed bed column mode, an appropriate amount of ion exchange was carried out to produce the mixed-salt API in the effluent stream. The resin bed could be regenerated using KCl solution and reused for subsequent batches of polymer solution. The recovery of the API in the product solution was excellent. The ion exchange route was used to synthesize radio-labeled API for clinical trials.     

INNOVATIVE APPROACHES TO SYNTHESIS OF GT 267-004, A SEQUESTRANT FOR C. DIFFICILE TOXIN

GT 267-004 is a nonabsorbed, nonantibiotic, high molecular weight anionic polymer that is undergoing clinical evaluation as a Clostridium difficile toxin sequestrant. The active pharmaceutical ingredient (API) is a mixed salt form that consists of approximately 30 to 50% potassium and 70 to 50% sodium as the counterions on the polymer. The initial polymerization process results in an aqueous polymer solution with the polymer in the 100% sodium form. This article describes the use of two innovative approaches, electrodialysis (ED) and ion exchange using ion exchange resins (IXR), to convert the single-salt polymer to the mixed-salt form. Electrodialysis experiments were conducted using a stack of five cells, each of which contained two cation and one anion exchange membranes. The electrodialysis was run in batch mode with a sodium chloride solution as the concentrate stream and a potassium chloride solution as the diluate stream. The ED process was monitored on-line by measuring the conductivity of the streams. Yield loss of the API through the ED membranes was minimal. The ED process was found to be fast, efficient, and reproducible. The ion exchange experiments were conducted using a strong acid cation resin in the potassium form. By using a fixed bed column mode, an appropriate amount of ion exchange was carried out to produce the mixed-salt API in the effluent stream. The resin bed could be regenerated using KCl solution and reused for subsequent batches of polymer solution. The recovery of the API in the product solution was excellent. The ion exchange route was used to synthesize radio-labeled API for clinical trials.     

KINETICS OF Na+-H-ION EXCHANGE IN CONCENTRATED BUFFER SOLUTIONS OF SODIUM TETRABORATE AND BORIC ACID

Na⁺-H⁺ ion exchange between a fixed bed of Lewatite S 100 cationic ion exchange resin in R-H form and concentrated NaCl solutions at room temperature (298 K) and sodium tetraborate solutions at elevated temperature (338 K) was studied both experimentally and theoretically.

In the prediction of the break-through curves intraparticle and film diffusion resistances were considered. The variation of diffusion coefficient with the composition of the solid and liquid phases was accounted for by application of a Nernst-Planck model.

The shape of the break-through curves is very different in the two systems studied. A very favourable shape in the case of Na⁺-H⁺ ion exchange from sodium tetraborate solutions is due to the influence of borate buffer properties on equilibrium. The results of the computer simulation are in good agreement with the experimental data.     

KINETICS OF ABSORPTION OF OXYGEN IN ALKALINE SOLUTIONS CONTAINING A QUINONE-TYPE COMPOUND

The rates of absorption of pure oxygen in alkaline aqueous solutions containing sodium salt of 1,4-naphthoquinone 2-sulfonic acid (NQS) as a catalyzer for the Takahax desulfurization process were measured at 25°C using a liquid jet column.

The kinetics of the absorption was examined based on the theory for gas absorption accompanied by an irreversible second order chemical reaction. The pH of the solution, that is, the concentration of hydroxyl ion plays an important role in a reaction of first order with respect to oxygen and to NQS. The reaction rate constant is directly proportional to pH in the range 9.8-11.5, for more alkaline solutions being found to be 4.5 × l0⁶L/mole • s.     

MEASUREMENT OF INTERFACIAL AREA AND MASS TRANSFER COEFFICIENTS BY CHEMICAL METHOD OF C02 ABSORPTION INTO AQUEOUS SOLUTIONS OF NaOH IN A MODEL COLUMN WITH EXPANDED METAL SHEET PACKING

The theory of gas absorption accompanied by fast pseudo-fast order reaction which considered dependences of diffusivity, kinetic constant and Henry's law constant on absolute temperature and ionic strength was used to obtain values of effective interfacial areas and mass transfer coefficients in gas and liquid phase.

Experimental measurement of carbon dioxide absorption from mixture with air was performed in a pilot-plant column with expanded metal sheet packing irrigated with sodium hydroxide solution.

Resulting liquid and gas-side mass transfer coefficients are compared with values obtained from physical Absorption measurement of carbon dioxide into water and with measurement of gas-side mass transfer coefficient for sulphur dioxide in the same column.

The differences between determined values are discussed.     

MASS-PRODUCTION OF BIOCATALYST-ENTRAPPING ALGINATE GEL PARTICLES BY A FORCED OSCILLATION METHOD

A forced oscillation method applying reverse-piezo electric effect has been proposed for mass-production of biocatalyst-entrapping polymer gel particles. A jet of aqueous alginate solution flowing out through an orifice was disintegrated into droplets by an oscillating pressure which was exerted by a ceramic plate vibrated by the reverse-piezo electric effect. The droplets formed were immediately solidified into gel particles in calcium chloride solution.

The particle production rate by the method was up to 270 particles s^-1 or 1 × 10^-6m³.s^-1 The size of the particles produced were down to I mm depending on the applied frequency. The smallest matrix size of the gel's polymer network was estimated to be around 5 nm.

The method was applied for immobilization of yeast cells. The diameter of immobilized particles was 2.5 mm. The immobilized yeast grew well in the particle. The damage of yeast cells caused by the immobilization was not remarkable     

RHEOLOGICAL AND MIST IGNITION PROPERTIES OF DILUTE POLYMER SOLUTIONS

A spinning disc atomizer has been used to characterize the mist flammability of Jet A and diesel fuels that contain high molecular weight polymers. The critical disc velocity required to produce significant flame propagation was shown to depend on polymer concentration, molecular weight, solvent viscosity, and polymer degradation.

The viscoelastic properties of these same polymer solutions have been characterized by a maximum Darcy viscosity measured from flow in packed tubes. For the polymers discussed in this paper, the maximum Darcy viscosity was independent of the bead size or tube length; however, it was strongly affected by the same variables that affected mist flammability; i.e., polymer concentration, molecular weight, solvent viscosity, and polymer degradation.

The critical ignition velocity of dilute polymer solutions is shown to depend on the Darcy viscosity in a similar manner as observed for viscous oils. At low viscosities, the ignition velocity is only slightly affected, but the dependence grows stronger as the viscosity (both shear and Darcy) increases. A close correspondence was also shown to exist between the ignition velocity of a polymer solution with a high Darcy viscosity and the ignition velocity of a Newtonian oil with approximately the same high shear viscosity.

Numerous similarities are described between flow-induced birefringence of dilute polymer solutions with opposed capillary jets and viscoelastic resistance of dilute polymer solutions in packed tubes. These similarities suggest that the maximum Darcy viscosity is associated with a condition of almost complete extension and alignment of the polymer molecules.     

MERCURY REMOVAL FROM OILS

Heavy condensate or oil can contain significant amounts of mercury which causes marketing, processing and environmental concerns.

We have developed an effective process to remove all kinds of mercury compounds in heavy condensate. At the conditions tested, the total mercury content in a condensate was reduced from 3,000 to lO ppb, representing 99.7% mercury removal.

In the process, the condensate is pumped upflow through a reactor filled with activated carbon and polysulfide solution at mild conditions. The effluent is a clear, low mercury product.

The theory and principles of the process are developed and verified with experiments. Process variables were also explored to define the preferred region of operation.     

SOLAR DRYING OF RAISING

The drying of Sultana seedless grapes was investigated under intermittent and continuous operating conditions in a laboratory solar installation involving a thermal storage bed and an auxiliary heater. The effect of pretreatment, and of the a i r velocity on the drying rate of the grapes at constant temperature was also studied in relation t o the quality of the dried product.

Solar drying of the grapes was accomplished in 30.5 to 60.5 h of intermittent operation, or 19 to 60 h of continuous drying, involving the thermal storage bed and the auxiliary heater. The shortest drying time (19 h ) and the highest quality dried product were obtained with grapes dipped in a hot (80 C ) solution of sodium hydroxide and ethyl oleate, which were dried continuously at 42°C and 2m/s, air temperature and velocity respectively.

The mean apparent diffusivity of moisture in raisins at 6o°C and air velocity 2m/s was estimated as 1.0.10-10 m2/s.     

EVALUATION OF PENG ROBINSON EQUATION OF STATE IN CALCULATING THERMOPHYSICAL PROPERTIES OF COMBUSTION GASES

A set of simple equations of the thermodynamic and transport properties of the combustion gases of a gas turbine have been derived based upon the critically evaluated data and two equations of state: The virial equation of state and Peng-Robinson (PR) equation of state.

The properties which have been considered were, density, specific heat at constant pressure, enthalpy, entropy, viscosity and thermal conductivity.

The temperature range was (200-2600 K) theoretically while the pressure range was (0.3-1.2 MPa).

A computer program, to evaluate the departure of thermophysical properties using virial and PR equations of state, was used.

The Peng Robinson (PR) equation of state gave better estimated accuracy than the virial equation of state especially in evaluating the departure of thermodynamic properties.     

A KINETIC MODEL FOR THE PRODUCTION OF LIQUIDS FROM THE FLASH PYROLYSIS OF BIOMASS

A kinetically based prediction model for the production of organic liquids from the flash pyrolysis of biomass is proposed. Wood or other biomass is assumed to be decomposed according to two parallel reactions yielding liquid tar and ( gas + char) The tar is then assumed to further react by secondary homogeneous reactions to form mainly gas as a product

The model provides a very good agreement with the experimental results obtained using a pilot plant fluidized bed pyrolysis reactor

The proposed model is shown to be able to predict the organic liquid yield as a function of the operating parameters of the process, within the optimal conditions for maximizing the tar yields, and the reaction rate constants compare reasonably well with those reported in the literature     

DEVELOPMENT AND VALIDATION OF A PROCESS SIMULATOR FOR DRYING SUBBITUMINOUS COAL

Drying subbituminous coal has never been practiced commercially. The commercial dryers built to date have been designed for drying surface moisture in conjunction with upstream coal preparation facilities. This type of drying is mainly controlled by input energy and the basis of the design is an energy balance. In drying inherent moisture from subbituminous coal, the thermal conductivity of the coal and the diffusion of molecular water within coal particles impose limitations on the process conditions. Energy input and solids residence time in the dryer have to be controlled properly for simultaneously balancing the heat and mass transfer within the coal particles. Improper control of either parameter can cause fires and explosions during the key steps of the drying process—drying and cooling

In parallel to the Anaconda coal drying pilot plant program, a cross-flow, fluid-bed coal drying/cooling process simulator was developed for: (1) understanding the drying phenomena on an individual particle basis; (2) analyzing potential risks and safety limits, and (3) designing the Anaconda pilot plant program

The development of the process simulator was based on both first principles and laboratory data and can be divided into two phases:

1 Development of a semi-mechanistic drying model for Powder River Basin subbituminous coal employing an analytical solution of the diffusion equation

2.Formulation of a fluid-bed cross-bed cross-flow dryer/cooler simulator employing simultaneous heat and mass transfer

This model was validated against process variables data taken on a 4 tph pilot plant. An operable range, or process envelope, has been developed through the pilot plant experience and the process simulation study. Based on the model predictions, an uncertainly range was defined in the design recommendations of a pioneer coal drying plant in scale-up.     

TAYLOR DISPERSION OF MULTICOMPONENT SOLUTES

Coupled transport of multicomponent solutes in globally continuous systems is considered in the framework of the Generalized Taylor dispersion theory. Coupling between transports of n different species at the local (or micro-) scale, is considered to result from first-order irreversible surface reactions occurring on the local space boundaries, or from the off-diagonal terms of the solute diffusivity matrices.

General expressions are obtained for the global effective (long-time) solute dispersion matrix cofficients: mean global scalar reactivity, velocity vector and dispersivity dyadic.

The effect of surface chemical reactions is to partition the matter between different solute constituents. This is manifested in a coupling of the global transport coefficients, which may be mathematically removed by a linear (canonic) transformation applied to the effective global transport equation. This type of coupling does not exist for inert solutes.

The second type of the global coupling is represented by the off-diagonal terms of the global velocity and dispersivity matrices. It exists for both reactive and inert solutes. This coupling stems from the convective dispersion process (dependence or the global velocity vector on the local space coordinate). Is shown to be irremovable from the global transport equation by any linear transformation via the solute partition matrix. In the canonic form of the global equation the irremovable coupling is manifested by the traceless parts of the global solute velocity matrix and the global solute dispersivity.

The solution scheme is illustrated by calculating the mean global diffusivity of a solute consisting of two components, transport of which is coupled at the microscale via the molecular diffusivity matrix. At the macroscale the coupling is shown to be represented by negative off-diagonal terms of the global diffusivity matrix,     

Adhesion of Plasticized Polyvinyl Butyral) to Glass

A study of safety glass provides a good example of the interplay among the many physical properties involved in “adhesion”, and the relationship between adhesion and performance. This work demonstrates the value of applying known fundamentals to practical problems.

An idealized model of a windshield fracture event is described in terms of interactions among mechanical responses of the interlayer, the fracture characteristics of the glass and the high speed, low angle peel behavior.

Data on the surface energies of glass, polyvinyl butyral) and water show that at thermodynamic equilibrium a stable system comprising glass, water and polyvinyl butyral) phases, an aqueous phase must lie between the glass and PVB.

The potassium salts are shown to be effective because they are deliquescent and give solutions at equilibrium with the water in the PVB at water contents of ∼0.40% or higher. The greater the amount of salt at the interface and the higher the water content of the sheeting during lamination, the thicker the interfacial layer and delamination occurs more readily. This relationship is quantified using a modified form of the Stefan equation.

Data on diffusion of water and salt are shown to be consistent with the amount of salt at the interface required for the observed performance (∼ 3 mg KAc/m²).

Data on electrical resistivity of the interface correlate with peel force and provide convincing support for the hypothesis.     

RECIRCULATING REACTOR FOR THE STUDY OF MULTIPHASE KINETICS

A new laboratory reactor was set up to measure kinetic coefficients in a solid (catalyst)-liquid-gas reacting system.

The reactor consists of two parts: an absorber, where the liquid is partially saturated by the gas reactant and a reacting zone, where the liquid alone, containing the dissolved gas, flows through a fixed bed of catalyst.

The ricircle of the liquid in the absorber maintains a high concentration of the gas reactant in the liquid also in the zone of reaction, allowing the use of a high mass of catalyst (significative from a statistical point of view) and the achievement of sufficiently high conversion.

The tested reaction is the catalysed hydrogenation of ∝-metylstyrene: in order to consider a drastic situation and to verify the results with the literature data, the experimental conditions examined corresponded to very high chemical reaction rate (instantaneous reaction) at the surface of the pellets.

The tests were carried out with the reactor working both in batchwise and in continuous operative mode (steady state); the results show the reliability of the new reactor above all when the steady state operation is considered. For the use of the reactor in batchwise condition, the accumulation of the product inside the catalyst particles must be considered for an accurate measurement of the kinetic parameters,     

EFFECT OF DEFORMATION SEQUENCE ON RHEOLOGICAL BEHAVIOUR AND MECHANICAL DEGRADATION OF POLYMER SOLUTIONS

The flow behaviour of polymer solutions of non-hydrolyzed polyacrylamide and Xanthan was investigated in two rectangular and similar plexiglas models containing 3 cylindrical enlargements of the same dimensions. These three enlargements were located successively at the mid point of the first model length, whereas they were equally spaced along the second one. Only non-hydrolyzed polyacrylamide polymer solutions have shown viscoelastic behaviour in these plexiglas models. However, the behaviour of these polymer solutions in the first model was different from that in the second one.

The multipass mechanical degradation of the non-hydrolyzed polyacrylamide polymer solutions was studied extensively in the two plexiglas models. It was shown that, at high flow rates, the multipass mechanical degradation was stronger in the second model than in the first one. The mechanical degradation in model 1 converges with that in model 2 as the flow rate decreases.

The difference in flow behaviour and mechanical degradation of the same polymer solutions in the used plexiglas models was ascribed to the different times allowed for polymer solutions to relax prior to extension in the tested flow fields.     

HEAT AND MASS TRANSFER IN THE SHORT-TERM CONTACT OF THE MOIST MATERIALS WITH THE HEATING SURFACE

Compounded boundary-valued problem of the diffusion-filtering heat and mass transfer with arbitrary dimensions of the transfer potential vector was raised and solved based on the theory of short-term contact between the moist material and heat-transfer surface.

The boundary lines of the application of the short-term contact models were established.

The solution of the problem allows to select the directions of the intensification of the drying processes with short-term contact of the phases and to calculate various technological characteristics of the drying processes.     

DEEP LAYER MALT DRYING MODELLING

In malt production drying operation plays an important role in the total processing cost, however there are not many studies on malt drying modeling and optimization.

In this paper a deep layer malt drying mathematical model in the form of four partial differential equations is presented.

To determine drying constants, malt thin layer drying experiments at several air temperatures and relative humidities were made.

The model were validated at industrial scale. The greatest energy savings, approximately 5 5% in fuel and 7.5% in electric energy, were obtained by an additional (and increased) air recirculation, which is carried out during the last 6 hours of the drying process and a significant decrease of air flow-rate during the last 6 hours of the drying process.     

MASS TRANSFER AND DIFFUSION COEFFICIENT DETERMINATION IN THE WET AND DRY SALTING OF MEAT

Dehydrated salted meat is widely used in Brazil as a very important source of animal protein. The main objective of this kind of processing is water removal. initially by osmotic pressure changes and then by drying, resulting in a product with intermediate moisture levels.

In this work, mass transfer and salt diffusion in pieces of meat submitted to wet and dry salting were studied. Slabs of beef m. trapezius with an infinite plate geometry were salted in a NaCl saturated solution or in a dry salt bed, at two temperatures (10 and 20°C) and different time exposures (120 min and 96 hours). Equilibration studies were extended up to six days.

It was observed that water loss increased with salt uptake, for increasing periods of times. At 20°C the moisture loss was higher than it was at 10°C in both salting processes. On the other hand, the kinetics of salt uptake and moisture loss were of greater importance in the process of dry salting than in that of wet salting.

The salt diffusion coefficient for wet salting was 0.26 × 10^-10m²/s at20°C and 0.25 × 10^-10 m²/s at 10°C and for the dry salting the values were 19.37 × 10^-10 m²/s at 20°C and 17.21 × 10^-10 m²/s at 10°C.