Membrane-assisted Crystallization Research Articles

Membrane assisted crystallization of active pharmaceutical ingredients (APIs) by forward osmosis and its effect on crystal size and morphology

At present and in the past decade, forward osmosis (FO) membrane technology has grown as an emerging technology in various area specially desalination, waste and drinkable water treatment, pharmaceutical, and food processing industry. FO depends on the osmotic pressure difference generated between feed solution (FS) and that of draw solution (DS) which results the separation of selective liquid components possible. FO is energy intensive process creating concentration gradient between FS and DS, which is driving force for separation and concentration of saturated solutions. Membrane assisted crystallization (MAC) process; a combination of membrane technology with conventional crystallization processes is useful hybrid crystallization process recently developing mostly in pharmaceutical and food processing sectors. In this work, comprehensive study has been done on the membrane assisted FO process which utilizes various operation conditions which are necessities for development of hybrid MAC for the active pharmaceutical ingredients (APIs). Recently developed membranes have intrinsic characteristics of operational simplicity, high permeability, selectivity and efficiency. These characteristics make possible to develop a technology which satisfies the concept of various APIs production. The main objective of this present study is to compare the effect of various process parameters such as drug solution supersaturation, crystallization temperature, and time on crystal size and morphology of APIs by conventional crystallization and MAC.

Macromolecular crystallization: basics and advanced methodologies

For the first time, about 155 years ago and as a laboratory curiosity, German biologists observed the crystals of hemoglobin from worms and fishes. Since then, the crystallization of proteins, nucleic acids and big biological structures, like viruses, has been developed into a broad research field including several applications, for example in the drug discovery. This review is divided into four major sections. The first section addresses the specific physicochemical properties of biomolecular crystals accompanied by kinetics of supersaturation, nucleation and growth which are the three main steps required to achieve macromolecular crystals. Besides, various physical, chemical and biochemical parameters influencing the process of macromolecular crystallization are reviewed. The second part deals with classical approaches, such as vapor and batch diffusion methods, available to create macromolecular crystals. The third part overviews novel approaches including microgravity, cocrystallization, membrane-assisted crystallization and microfluidic array chips involved in more complicated techniques for growing macromolecular crystals and controlling their size and orientation. In the end, considering the very significant role of automation in providing biomolecules’ crystals in recent years, we provided a brief explanation about robotics and their importance in developing high-throughput crystallization. RDC-NMR and SAXS/WAXS hybrid methods with the aim of obtaining structural information of complex macromolecular assemblies are also discussed.

Modeling of Membrane-Assisted Seeded Batch Crystallization

In this work, the operation of membrane-assisted seeded batch crystallization is modeled for five substances: potassium nitrate, potassium sulfate, pentaerythritol, succinic acid, and potassium alum. The effect of seed loading, seed size, and water removal rate on product crystal size is investigated. Seed loading and seed size were found to have a significant impact on product crystal size for a given batch time and product yield. Trajectories for the optimal water removal rate versus time were also determined. Overall, the results show that membrane-assisted crystallization behaves similarly to other types of crystallization in terms of product crystal size and size distribution while having the potential to reduce cost and equipment size.

Membrane-Assisted Crystallization: A Molecular View of NaCl Nucleation and Growth

Membrane-assisted crystallization, aiming to induce supersaturation in a solution, has been successfully tested in the crystallization of ionic salts, low molecular organic acids, and proteins. Membrane crystallization is an emerging membrane process with the capability to simultaneously extract fresh water and valuable components from various streams. Successful application of crystallization for produced water treatment, seawater desalination, and salt recovery has been demonstrated. Recently, membrane crystallization has been developed to recover valuable minerals from highly concentrated solutions, since the recovery of high-quality minerals is expected to impact agriculture, pharmaceuticals, and household activities. In this work, molecular dynamics simulations were used to study the crystal nucleation and growth of sodium chloride in bulk and with hydrophobic polymer surfaces of polyvinylidene fluoride (PVDF) and polypropylene (PP) at a supersaturated concentration of salt. In parallel, membrane crystallization experiments were performed utilizing the same polymeric membranes in order to compare the experimental results with the computational ones. Moreover, the comparison in terms of nucleation time between the crystallization of sodium chloride (NaCl) using the traditional evaporation process and the membrane-assisted crystallization process was performed. Here, with an integrated experimental–computational approach, we demonstrate that the PVDF and PP membranes assist the crystal growth for NaCl, speeding up crystal nucleation in comparison to the bulk solution and leading to smaller and regularly structured face-centered cubic lattice NaCl crystals. This results in a mutual validation between theoretical data and experimental findings and provides the stimuli to investigate other mono and bivalent crystals with a new class of materials in advanced membrane separations.

Economic Comparison of Crystallization Technologies for Different Chemical Products

Crystallization is an ancient unit operation that remains vital for the chemical process industry. Traditional single-effect evaporation consumes a great deal of energy, and various alternatives to this method have been proposed. In this work, the total cost of producing a fixed quantity of different solid chemicals by crystallization from water is determined for several different technologies: evaporative crystallization, membrane distillation with porous hydrophobic membranes, reverse osmosis membrane-assisted crystallization, and eutectic freeze crystallization (EFC). Among the solute properties, the solubility has the greatest effect on the cost of the process since it determines the amount of water that must be removed per unit product produced. If waste heat is available at a unit price lower than that of low-pressure steam produced using coal or natural gas, then the assumed price of waste heat also has a significant effect on the economics. The results indicate that, if feasible, reverse osmosis h...

Perspectives on mining from sea and other alternative strategies for minerals and water recovery – The development of novel membrane operations

Abstract An important contribution to the realization of a sustainable industrial development can be given by membrane operations. They can contribute to redesign process engineering in the logic of process intensification. In particular, the results achieved with membrane-assisted crystallization and membrane-assisted condensation show as these innovative membrane operations can overcome the performance of traditional operations: in the case of MCr, the possibility to produce specific polymorphs of crystals; in the case of the condenser, the control of the concentration of condensable contaminants in the recovered liquid stream. These two innovative membrane operations can bring interesting results for “water recovery from sky” and “water and mineral extraction from the sea”.

Testing of three different PVDF membranes in membrane assisted-crystallization process: Influence of membrane structural-properties on process performance

Throughout the world an intensified use of desalination for reducing current and future water scarcity is observed. Despite the enormous benefits of desalination processes, improvements are still required in terms of lower desalted water cost, higher productivity, better water quality and enhanced eco-sustainability of the desalination process. Environmentally sensitive concentrate management is today recognized as a significant hurdle to extensive implementation of desalination technologies. Membrane assisted crystallization (MCr) offers a suitable solution for redesigning desalination process through the treatment of brine streams for the production of salts and water. In this work, three different Hyflon/polyvinylidene fluoride (PVDF) composite membranes were tested in MCr operations. The coating of PVDF membranes with Hyflon allowed increasing membrane surface hydrophobicity. The latter is the membrane essential characteristic when MCr is implemented according direct contact membrane distillation configuration like in the present work. The aim was to analyze the MCr performance in terms of membrane chemical–physical properties and process operating conditions.

Design and economic analysis of membrane-assisted crystallization processes

Abstract Reverse-osmosis (RO) and porous hydrophobic membranes have attracted attention as an alternative to conventional evaporation for crystallization processes, the latter being recommended especially if low-grade waste heat is available to provide the enthalpy of vaporization. In this work, these two types of membrane-assisted processes are designed and costs are compared with those of conventional single or multiple-effect vacuum evaporation processes. When waste heat is not available, RO processes are shown to be the least expensive because the pumping costs, while significant, are more than offset by the fact that it is not necessary to provide the enthalpy of vaporization of the solvent. When waste heat is available, a conventional evaporation process is favorable because it can also be powered by the waste heat and does not require the capital cost for the membranes.

Continuous Membrane-Assisted Crystallization To Increase the Attainable Product Quality of Pharmaceuticals and Design Space for Operation

Continuous manufacturing is an important paradigm shift in pharmaceutical industries and has renewed the interest in continuous crystallization. The combination of crystallization and membranes is a promising hybrid technology for separation and purification of pharmaceuticals. The impact of membranes as an extension to conventional continuous crystallization processes on attainable product quality and design space is investigated systematically using model-based optimization. The proposed model is based on a full population balance such that all relevant crystallization phenomena can be included and is solved using a first-order discretization scheme with a hybrid grid. A case study involving continuous crystallization of paracetamol using a series of mixed suspension, mixed product removal (MSMPR) crystallizers is presented to illustrate the approach. The results show that the attainable size and design space can be enlarged significantly by extending conventional crystallization with membranes. In part...

Membrane-assisted crystallization: Membrane characterization, modelling and experiments

A hollow fiber membrane module was assessed for its potential in assisting crystallization processes. The membrane module was characterized in the sweeping gas membrane distillation configuration considering various solution and sweeping gas flow rates, temperatures and solution concentrations. A model, coupling mass and heat transfer, was developed to predict the membrane flux. The effect of the process conditions on the membrane flux was experimentally determined and the results were used to validate the model. Feed temperature and air flow rate were found to have a significant effect on the membrane flux. Having found the optimal process conditions for membrane distillation process, batch seeded crystallization experiment were performed to confirm the potential of membrane distillation in the generation of adequate rate and level of supersaturation. Since the desired supersaturation level could be maintained in the crystallizer while seeds were growing, it is confirmed that membrane distillation can be an efficient alternative to conventional supersaturation generation processes. Finally, comparing the modelling results with experiments confirms the acceptable accuracy and predictability capability of the developed model.

Enhanced performance of a biomimetic membrane for Na2CO3 crystallization in the scenario of CO2 capture

Membrane assisted crystallization (MACr) offers an innovative platform for crystallizing Na2CO3, allowing its reuse after CO2 capture from flue gases by an alkaline solution (i.e., NaOH). In this study, the biomimetic aquaporin Inside™ membrane AIM60 was employed to enhance water removal, facilitating Na2CO3 crystallization. The water channel in the active layer, comprising aquaporin proteins, and the strong wettability of membrane substrate assist a better performance. For instance, the water flux of AIM60 membrane for concentrating a 1.89molL−1 Na2CO3 solution (osmotic pressure of 94.8bar) in forward osmosis (FO) mode was 6.62Lm−2h−1 and 3.25Lm−2h−1 in pressure retarded osmosis (PRO) mode when a 5.13molL−1 NaCl solution (osmotic pressure of 304.9bar) was employed as the draw solution. This demonstrates that the AIM60 FO membrane outperformed the previously reported dense reverse osmosis membrane (0.21Lm−2h−1 in FO mode and 0.16Lm−2h−1 in PRO mode) and a porous hydrophobic hollow fiber membrane (0.08Lm−2h−1) under the same operating conditions.Crystallization utilizing the AIM60 membrane in an osmotic crystallizer was achieved without noticeable membrane scaling or degradation. Furthermore, a proper control of the supersaturation level induces crystallization of Na2CO3·10H2O crystals with a purity of 99.94%. Hence, the aquaporin Inside™ FO membrane may be a promising alternative to existing methods for Na2CO3 crystallization for its application in a CO2 capture scenario.

Membrane Crystallization of Sodium Carbonate for Carbon Dioxide Recovery: Effect of Impurities on the Crystal Morphology

Membrane contactors have been proposed as an advanced tool for CO2 capture from flue gases by absorption in alkaline solutions. However, regeneration of the alkaline reagent and further CO2 sequestration are pending issues. In this paper, membrane-assisted crystallization is proposed for crystallizing Na2CO3, which allows its reuse, after CO2 absorption from flue gases. Due to the presence of compounds other than CO2 in flue gases (i.e., SO2, NOx), other compounds (Na2SO4 and NaNO3) may interfere with Na2CO3 crystallization. This was evaluated by measuring the flux through the membrane and the morphology, crystallography, and purity of the crystals. Furthermore, the presence of NaCl possibly transferred from the osmotic solution to the feed solution was evaluated. The experimental results indicate that the presence of impurities decreases the flux through the membrane due to the decrease of water activity, although there is no influence on the overall mass transfer coefficient. The presence of Na2SO4 affected the morphology of the Na2CO3 crystals while NaNO3 and NaCl had no apparent effect on the crystalline products. It was confirmed that Na2CO3•10H2O was formed during the crystallization. Moreover, the purity of Na2CO3 crystals reaches up to ca. 99.5%. Membrane-assisted crystallization was concluded to be feasible in recovering CO2 as a carbonate salt, which can possibly be reused in the industry.

Supersaturation Control and Heterogeneous Nucleation in Membrane Crystallizers: Facts and Perspectives

The interest to combine membrane operations and solution crystallization has grown in the past several years. This approach has been put into practice in several forms of membrane-assisted crystallization (MAC) processes, among which is membrane crystallization (MCr) technology. The main features of MCr are (1) the use of membranes as precision devices to control the composition of the crystallizing solution, by opposing a well-defined and tunable resistance to mass flow occurring in the vapor phase; (2) the action of the porous surface of the membrane as a suitable support to activate heterogeneous nucleation mechanisms; (3) the possibility to induce nucleation and crystal growth in separate sites, thus reducing the risk of membrane fouling even when the same membrane supports heterogeneous nucleation. Thanks to these fundamental options, combined together in a unique apparatus, advantages like (i) improved control of the supersaturation degree and the rate of its generation; (ii) the possibility for the crystallization to be initiated at low supersaturation levels; (iii) the enhancement of the crystallization kinetics; and (iv) improved overall process efficiency can be achieved, even for large and complex molecules like proteins. The most interesting developments and the more exciting perspectives for this novel technology have been reviewed in this paper.

Characterization and Dynamic Optimization of Membrane-Assisted Crystallization of Adipic Acid

The concept of membrane-assisted crystallization using reverse osmosis (MaC-RO) shows a high potential in decreasing energy conversion as compared to evaporative crystallization. A setup has been constructed for MaC-RO, using two separate loops for membrane separation and crystallization. In this study we focus on the characterization of the membrane performance in solvent removal from an aqueous adipic acid solution under reverse osmosis conditions. A semiempirical model was developed for the flux as a function of temperature, concentration, and pressure difference across the membrane. The presence of adipic acid strongly reduces the flux at the same feed temperature and pressure, as compared to the flux from a pure water feed. This effect could be attributed to competitive adsorption on the membrane surface and, to a lesser extent, concentration polarization. For a batch MaC-RO process a dynamic optimization was conducted by changing the operational policy (membrane feed pressure, flow rate, and tempera...

Heterogeneous nucleation of calcium oxalate crystals in the presence of membrane vesicles

Membrane-assisted crystallization of calcium oxalate was studied in vitro, using constant composition methodology. Rat renal tubular brush border membrane vesicles were incubated in supersaturated solution of calcium oxalate. Calcium and oxalate depletion started much earlier in the presence of the vesicles than in their absence; within 8, 32, or 258 min of the incubation of vesicles in calcium oxalate solutions of relative supersaturation of 12, 10 or 6 respectively. Thin plate-like crystals with jagged edges formed in association with the membrane vesicles. Since crystal nucleation in the presence of membrane vesicles started within 8 min at a relative supersaturation as low as 12, it will start significantly earlier in the urine of stone formers which is known to have higher relative supersaturation with respect to calcium oxalate. These results demonstrate that cellular membranes can efficiently induce nucleation of calcium oxalate crystals from a metastable solution in an vitro system. Similar membrane induced heterogeneous nucleation of calcium oxalate in vivo within the renal tubules is a distinct possibility.