Downstream Separation Research Articles

Synergizing autothermal reforming hydrogen production and carbon dioxide electrolysis: Enhancing the competitiveness of blue hydrogen in sustainable energy systems

With the global energy paradigm shifting towards renewable and sustainable systems, hydrogen is increasingly recognized as a promising energy carrier. In this transition, blue hydrogen is often considered a bridge solution to green hydrogen due to its economic vulnerability to carbon costs and environmental regulations related to life-cycle emissions. To expand the role of blue hydrogen, it is essential to enhance hydrogen yield, reduce production costs, and minimize greenhouse gas emissions during the production phase. This study proposes an integrated process for blue hydrogen production and CO2 electrolysis to enhance the competitiveness of blue hydrogen in sustainable energy systems. The focus of this study was to integrate autothermal reforming hydrogen production with solid oxide CO2 electrolysis and to determine the optimal configuration and operating conditions of the integrated process. The proposed process demonstrated superior performance in terms of energy efficiency, production cost, and environmental impact compared with conventional blue hydrogen production. Furthermore, considering the intermittency of renewable electricity and the uncertainties in CO2 electrolysis technology, the industrial feasibility of the proposed process was validated. The integration of autothermal reforming blue hydrogen production and CO2 electrolysis has four clear advantages: (i) the costly air separation and carbon capture units, which pose significant financial burdens in autothermal reforming blue hydrogen production, can be eliminated; (ii) the downstream separation, which is indispensable in a standalone CO2 electrolysis system, can be removed; (iii) utilization pathways for captured CO2 from blue hydrogen production have been proposed; and (iv) guidelines have been provided for the industrial utilization of CO2 electrolysis.

Flow-electrode capacitive separation of organic acid products and recovery of alkali cations after acidic CO2 electrolysis

Acidic CO2 electrolysis, enhanced by the introduction of alkali cations, presents a strategic approach for improving carbon efficiency compared to processes conducted in neutral and alkaline environments. However, a significant challenge arises from the dissolution of both organic acids and alkali cations in a strongly acidic feed stream, resulting in a considerable energy penalty for downstream separation. In this study, we investigate the feasibility of using flow-electrode capacitive deionization (FCDI) technology to separate organic acids and recover alkali cations from a strongly acidic feed stream (pH ~ 1). We show that organic acids, such as formic acid and acetic acid, are retained in molecular form in the separation chamber, achieving a rejection rate of over 90% under all conditions. Alkali cations, such as K+ and Cs+, migrate to the cathode chamber in ionic form, with their removal and recovery significantly influenced by their concentration and the pH of the feed stream, but responding differently to the types and concentrations of organic acids. The energy consumption for the removal and recovery of K+ is 4 to 8 times higher than for Cs+, and the charge efficiency is significantly influenced by the types of organic acid products and alkali cations. We conduct a series of electrochemical measurements and analyze the impedance spectroscopy, identifying that hindered mass transfer governed the electrode process. Our findings underscore the potential of FCDI as an advanced downstream separation technology for acidic electrocatalysis processes.

Process development and environmental impact assessment of sustainable poly(3-hydroxybutyrate) separation and purification via Paraburkholderia sacchari cell lysis using crude enzymes

Downstream separation and purification of poly(3-hydroxybutyrate) has been developed via combined crude enzyme bacterial cell lysis followed by solvent extraction and circular utilisation of bacterial lysate as nutrient supplement for PHB production. Enzymatic lysis of Paraburkholderia sacchari cells was initially evaluated using crude enzymes produced via solid state fermentation of Aspergillus oryzae. The optimum protease activity (156 U per g cell dry weight) resulted in 66.9% lysis of residual cell weight. PHB purification with 1,3-dioxolane, dimethyl carbonate, anisole, ammonium laurate and chloroform were evaluated at different processing parameters (extraction duration, temperature) using wet and dry bacterial cells as well as enzymatically lysed wet bacterial cells. The highest recovery yield (94.5%) and purity (98.1%) were obtained with 1,3-dioxolane at 80°C and 6h processing time using enzymatically disrupted bacterial cells. The bacterial cell lysate was used as nutrient supplement for circular PHB production in fed-batch P. sacchari bioreactor cultures leading to the production of 78.7 gPHB/L, 56.9% (w/w) PHB content and 2.3g/(Lꞏh) productivity. Low global warming potential (1.3 CO2-eq/kgPHB) and abiotic depletion fossil (14.4 MJ/kgPHB) were estimated for PHB purification via enzymatic cell lysis and PHB extraction with 1,3-dioxolane demonstrating the development of a sustainable and circular process for PHB production.

Comprehensive techno-economic and environmental assessment for 2,3-butanediol production from bread waste

Bread waste (BW) is a common food waste in Europe and North America and has enormous potential as a biorefinery substrate for the sustainable synthesis of various platform chemicals. Our previous work made use of BW for the fermentative production of 2,3–butanediol (BDO). The present work evaluated the economic prospects and environmental consequences associated with the overall processes, handling 100 metric tons BW per day. The comprehensive process design using Aspen Plus and integrated techno-economic and environmental assessment was carried out for two different BW hydrolysis scenarios: acid and enzyme hydrolysis, followed by fermentation and extraction-based downstream BDO separation. The optimal heat exchanger network was designed using pinch analysis, which improved the energy efficiency of the process significantly, with about 10 % savings of BDO production costs. Despite this improvement, the BDO derived from BW was exorbitant (4.2–6.9 $/kg) compared to the market price (3.23 $/kg) due to relatively higher capital investment for the current plant capacity. Further, the process inventory was modelled in SimaPro v9.1.0 to estimate the environmental consequences of these production processes for impact categories, such as global warming (2.63 – 3.19 kg CO2 eq.), marine eutrophication (3.55 × 10-4 – 4.01 × 10-4 kg N eq.), terrestrial ecotoxicity (6.44 – 7.88 kg 1,4 − DCB), etc. Sensitivity and uncertainty analyses were also conducted to establish the reliability of the results. It was found that the enzyme hydrolysis was associated with lower environmental impacts than acid hydrolysis. This comprehensive study can be used as a guideline for developing sustainable BW-based biorefinery in the future.

Scalable membrane-assisted ion exchange (MEM-IE) strategy for organic acid purification in biorefinery process

The transition towards a carbon-neutral society necessitates radical approaches in the bio-refinery pipeline, particularly in the production of organic acids. The current downstream process from a dilute fermentation broth is limited by the extensive use of acids and bases, along with heavy reliance on energy-intensive distillation. In this work, we propose an entirely membrane-based process to purify organic acids (e.g., gluconic acid) from a crude solution of catalytic dehydrogenation of glucose. To facilitate downstream purification, we introduce an innovative membrane-assisted ion exchange (MEM-IE) strategy, which is a scalable process that can protonate ionic compounds entirely in the solution phase. Instead of a solid ion exchange resin, a bulky yet soluble acidification agent is used to protonate the target compound, which can be easily separated via a size exclusion membrane. We selected non-toxic poly (4-styrene sulfonic acid) (H-PSS, 75 kDa) as the acidification agent to selectively protonate gluconate ions and to enable facile fractionation. The proposed MEM-IE strategy can overcome the scale-up limitation of traditional solid ion exchange resins and can be applied to many types of ionic compounds. The versatility of the proposed process was also demonstrated on formate and lactate compounds. A techno-economic evaluation using the Verberne cost model showed that the proposed process achieves an 80 % reduction in energy consumption compared to the fermentation-based process, and the return on investment (ROI) of a 330 ton-per-day plant was less than a year. The proposed membrane-based process for the purification of organic acids, particularly the MEM-IE strategy, offers a sustainable and energy-efficient downstream separation platform.

Development of membrane bioreactor for conversion of flue Gas-CO2 to C1 and C2 biomolecules

The capture and utilization of CO2 (CCU) from flue gases constitute a novel carbon feedstock for producing renewable chemicals and fuels. To lower the energy demand of CCU, Bio-Integrated Carbon Capture and Utilization (BICCU) was recently presented, where CO2-consuming microorganisms simultaneously desorb and convert CO2 captured from flue gas by methyl diethanolamine (MDEA) with H2 from water-electrolysis as the electron donor. The limiting factor is the microbial toxicity of MDEA, which restricts the capacity of the process. Furthermore, producing soluble molecules like the C2 platform molecule acetate is not possible without contaminating the product with capture agent. To resolve both challenges, we here propose a three-phase membrane system, where the MDEA and microorganisms are separated by a CO2-permeable membrane. Biological batch experiments with a mixed mesophilic culture confirmed the increased capacity of the BICCU-process for producing both methane and acetate when introducing a CO2-permeable membrane to the system to alleviate microbial inhibition by the capture agent and avoid contamination of soluble bioproducts. When using O2-rich flue gas from a biogas combustion engine, the CO2 conversion rate decreased by 18.0 % compared to a clean 20:80 CO2:N2 gas mixture, yet anaerobic metabolisms were still active in the mixed inoculum. Abiotic experiments furthermore showed that the microbial CO2 consumption maintained the gradient across the membrane and enhanced the CO2-flux by a factor of 3.1 ± 0.3. The membrane-based BICCU concept is expected to hold great promise particularly for producing acetate from flue gas-CO2, as the in situ separation eliminates the need for costly downstream separation.

Stability enhancement using a new combined casing treatment strategy in an ultra-highly loaded transonic compressor rotor

Low-reaction compressors are promising for achieving high loads but face severe flow instability challenges. This study investigates a low-reaction transonic compressor rotor using casing treatment technologies to control unstable flow dynamics precisely. First, a design integrating self-recirculating and circumferential groove casing treatments near the leading edge is implemented. This design enhances flow capacity at the tip passage inlet. However, it causes a “stall transposition” phenomenon. The unstable flow structures shift from shock-tip leakage vortex interactions at the front to corner separation at the rear. Consequently, the stall mechanism transitions from an end-wall stall to a blade stall. To address this issue, a new casing treatment layout is proposed. Grooves are added after the mid-chord of the initial front casing configuration. This adaptation suppresses emerging unstable flow structures and extends the stall margin by approximately 12.07 %. Detailed flow field analysis shows that the rear grooves effectively reduced the trailing edge separation vortex. They also limit downstream corner separation and mitigate disturbances from tip leakage flows in the rear of the passage.

Reactive extraction of muconic acid by hydrophobic phosphonium ionic liquids - Experimental, modelling and optimisation with Artificial Neural Networks

Muconic acid is a six-carbon dicarboxylic acid with conjugated double bonds that finds extensive use in the food (additive), chemical (production of adipic acid, monomer for functional resins and bio-plastics), and pharmaceutical sectors. The biosynthesis of muconic acid has been the subject of recent industrial and scientific attention. However, because of its low concentration in aqueous solutions and high purity requirement, downstream separation presents a significant problem. Artificial Neural Networks and Differential Evolution were used to optimize process parameters for the recovery of muconic acid from aqueous streams in a system with n-heptane as an organic diluent and ionic liquids as extractants. The system using 120 g/L tri-hexyl-tetra-decyl-phosphonium decanoate dissolved in n-heptane, pH of the aqueous phase 3, 20 min contact time, and 45 °C temperature assured a muconic acid extraction efficiency of 99,24 %. Low stripping efficiency compared to extraction efficiency was observed for the optimum conditions on the extraction step (120 g/L ionic liquids dissolved in heptane). However, re-extraction efficiencies obtained for the recycled organic phase in three consecutive stages were close to the first extraction stage. The mechanism analysis proved that the analysed phosphonium ionic liquids (PILSs) extracts only undissociated molecules of muconic acid through H-bonding.

Structural study of a light chain mispaired bispecific predicts mechanism of downstream separation

Bispecific antibodies expressed and assembled from a single upstream culture require the correct balance and pairing of four different heavy and light chains (HC and LC). The increased potential for chain-mispaired species challenges the downstream purification of this new format. While clearance of HC-mispaired species, including homodimers and half-antibodies, has been assessed, removal of LC mispairs requires a more stringent approach. Here, we report two case studies in which separation is achieved, as well as the structural basis of these separations: (A) In the first case, a main species with a positively charged patch in the correctly formed variable fragment (Fv) is disrupted when paired with the wrong LC. This LC-mispaired variant binds more weakly to a cation exchange resin and can be washed off in a chromatography step. (B) A second molecule whose LC mispair introduces a negative-charge patch and hydrophobic patch in close proximity, presenting increased binding to a multimodal anion exchange resin. This LC-mispaired variant can be retained on the column under conditions in which the bispecific is recovered. In both case studies, the molecular structural analysis by protein surface properties models correlated well with the chromatography experiments. The comprehensive interpretation of experimental and computational results has provided a better understanding of strategies and potential applications for predicting the downstream purification of complex molecules.

Carbon utilization in natural gas-based hydrogen production via carbon dioxide electrolysis: Towards cost-competitive clean hydrogen

Conventional blue hydrogen production still leads to direct carbon emissions, as well as significant energy consumption and costs for carbon dioxide (CO2) capture. CO2 electrolysis, which is one of the promising carbon utilization technologies, faces challenges beyond cell performance, including downstream separation. To address these issues, this study proposes a novel hydrogen production process integrated with CO2 electrolysis. Four integrated processes were developed based on two types of CO2 electrolysis in which cathode separation was either included or excluded. These integrated processes eliminate atmospheric carbon emissions from fossil-fuel-based hydrogen production without requiring a carbon capture unit; furthermore, the hydrogen yield increases. These processes were evaluated in terms of energy efficiency (EE), levelized cost of hydrogen (LCOH), and process carbon emission (PCE). Among the developed processes, the high temperature CO2 electrolysis without cathode separation (HT-CO2EL(w/oSep)) process exhibited the lowest LCOH and PCE. These findings demonstrate that proposed process effectively addresses the challenges associated with downstream separation and upstream heating inherent in standalone CO2 electrolysis systems. Compared with conventional blue hydrogen production, the HT-CO2EL(w/oSep) process achieved 22.2% improvement in EE, 12.0% reduction in LCOH, and 82.0% decrease in PCE. Sensitivity analysis shows that the proposed process remains economically viable compared to conventional blue and green hydrogen and is more adaptable to market fluctuations. The improvement in cell performance is expected to contribute to cost savings. Even accounting for methane leakage and carbon taxes, the process shows only a modest increase in total carbon emissions and LCOH.

A Review of Fucoxanthin Biomanufacturing from Phaeodactylum tricornutum.

Microalgae, compared to macroalgae, exhibit advantages such as rapid growth rates, feasible large-scale cultivation, and high fucoxanthin content. Among these microalgae, Phaeodactylum tricornutum emerges as an optimal source for fucoxanthin production. This paper comprehensively reviews the research progress on fucoxanthin production using Phaeodactylum tricornutum from 2012 to 2022, offering detailed insights into various aspects, including strain selection, media optimization, nutritional requirements, lighting conditions, cell harvesting techniques, extraction solvents, extraction methodologies, as well as downstream separation and purification processes. Additionally, an economic analysis is performed to assess the costs of fucoxanthin production from Phaeodactylum tricornutum, with a comparative perspective to astaxanthin production from Haematococcus pluvialis. Lastly, this paper discusses the current challenges and future opportunities in this research field, serving as a valuable resource for researchers, producers, and industry managers seeking to further advance this domain.

Direct conversion of lignin to liquid hydrocarbons for sustainable biomass valorization

Lignin, a principal biomass component, is a promising resource for manufacturing value-added products, tackling environmental concerns, and fostering sustainable energy alternatives. However, its intricate structure and recondensation reactions pose substantial conversion challenges. This study introduces an innovative one-pot catalytic technique for lignin’s direct conversion into liquid hydrocarbons over a Ru/C catalyst. The method integrates lignin depolymerization and the hydrogenolysis of resultant phenolics, achieving an 84.3 % carbon yield mainly constituting benzene, toluene, xylene, and cycloalkanes. The solvent-free concept in this system is proposed and tested, it streamlines downstream separation and boosts energy efficiency. These findings highlight the viability of repurposing waste lignin into liquid hydrocarbons and high-value chemicals, thereby supporting sustainable biomass utilization advancements.

Optimal design and operation of reactive distillation systems and reactive dividing wall systems with pressure swing distillation and hybrid distillation-pervaporation

Process intensification is essential in exploring more energy-efficient processes, and key examples related to fluid separations are reactive distillation and hybrid distillation-pervaporation processes. This work will consider the reaction and separation of a general quaternary reactive system with a minimum boiling binary azeotrope AC, in a reactive distillation column where, given the thermodynamics limitations, further downstream separation is required. Low and high chemical equilibrium is considered for the reaction. For the downstream purification, both pressure swing distillation and a hybrid distillation-pervaporation process are considered. For each of the structures, their intensified equivalent dividing wall structures are also considered, including a hybrid reactive dividing wall system. It is shown that reactive distillation followed by a hybrid distillation-pervaporation system can save up to 24% energy compared to reactive distillation with pressure swing separation, and that the dividing wall column counterpart structures have lower production-based total annualised costs than the corresponding base systems.

Carbon‐Efficient CO2 Electrolysis to Ethylene with Nanoporous Hydrophobic Copper

AbstractElectrochemical carbon dioxide (CO2) reduction offers a low‐carbon route to ethylene, when powered from renewable energy. Yet, the best‐performing CO2 electrolysis systems employ neutral or alkaline electrolytes, resulting in low conversion efficiencies, which increases downstream separation costs. High conversion rates can be achieved with acidic electrolytes, albeit at the cost ethylene faradaic efficiency (FE < 45%). As a result, achieving high ethylene selectivity simultaneously with high conversion efficiency is an unmet challenge. Here, a 3D‐nanoporous catalyst is designed to modulate water and CO2 concentration at the catalyst surface, reaching higher ethylene selectivity in a forward‐bias bipolar MEA that recovers unreacted CO2. An ethylene FE of 63% at 150 mA cm−2 is reported, and by optimizing for conversion efficiency, an ethylene FE of 58% along with an overall conversion efficiency of 82% is achieved. Stable performance for > 65 h at industrial current densities combined with a high ethylene concentration in the product stream showcases promising industrial viability.

Enhancing Recovery of Ultra-Fine Magnetite from Low-Iron-Grade Cyanidation Tailings by Optimizing Flow Field Parameters of Low-Intensity Magnetic Separation (LIMS)

The characteristics of iron minerals in cyanidation tailings with a low iron grade were determined via chemical composition analysis, iron phase analysis, and mineral liberation analysis (MLA). The results showed that the cyanidation tailings contained 15.68% iron, mainly occurring in the form of magnetite (19.66%) and limonite (79.91%), in which 16.52% magnetite and 65.90% limonite particles were fully liberated. Most ultra-fine magnetite grains were adjacent and wrapped with limonite to form complex intergrowths, which resulted in low-efficiency magnetite recovery in low-intensity magnetic separation (LIMS) and adversely affected the downstream high-gradient magnetic separation (HGMS) process. Thus, in this work, the optimization of the flow field was proposed to enhance the separation of ultra-fine magnetite from the cyanidation tailings using pilot-scale LIMS separation, and the controllable parameters (including feed flow, separation gap, drum rotating speed, and solid weight) affecting ultra-fine magnetite capture were investigated. Under optimized conditions, a high-grade magnetite concentrate assaying 63.31% Fe with 86.46% magnetite recovery was produced, which, respectively, increased by 0.76% and 15.22%, compared with those obtained from industrial production. In addition, from the flow dynamics simulation, it was found that the magnetite particles in the −6 µm ultra-fine fraction were lost much more easily than those of coarser fractions due to the relatively enhanced hydrodynamic drag force acting on the particles compared with the magnetic force. However, this loss would be effectively reduced with the regulation and control of the flow field. The iron recoveries in the −16~+6 µm and −6 µm fractions of magnetite concentrate increased by 3.66% and 4.42%, respectively, under optimized hydrodynamic conditions. This research outcome provides a valuable reference for the economic and effective utilization of iron resources from such solid wastes.

Techno-economic viability of bio-based methyl ethyl ketone production from sugarcane using integrated fermentative and chemo-catalytic approach: Process integration using pinch technology

Butanediols are versatile platform chemicals that can be transformed into a spectrum of valuable products. This study examines the techno-commercial feasibility of an integrated biorefinery for fermentative production of 2,3-butanediol (BDO) from sucrose of sugarcane (SC), followed by chemo-catalytic upgrading of BDO to a carbon-conservative derivative, methyl ethyl ketone (MEK), with established commercial demand. The techno-economics of three process configurations are compared for downstream MEK separation from water and co-product, isobutyraldehyde (IBA): (I) heterogeneous azeotropic distillation of MEK-water and extractive separation of (II) MEK and (III) MEK-IBA from water using p-xylene as a solvent. The thermal efficiency of these manufacturing processes is further improved using pinch technology. The implementation of pinch technology reduces 8% of BDO and 9–10% of MEK production costs. Despite these improvements, raw material and utility costs remain substantial. The capital expenditure is notably higher for MEK production from SC than BDO alone due to additional processing steps. The extraction based MEK separation is the simplest process configuration despite marginally higher capital requirements and utility consumption with slightly higher production costs than MEK-water azeotropic distillation. Economic analysis suggests that bio-based BDO is cost-competitive with its petrochemical counterpart, with a minimum gross unitary selling price of US$ 1.54, assuming a 15% internal rate of return over five-year payback periods. However, renewable MEK is approximately 16–24% costlier than the petrochemical route. Future strategies must focus on reducing feedstock costs, improving BDO fermentation efficacy, and developing a low-cost downstream separation process to make renewable MEK commercially viable.

Self‐Powered System for H2 Production and Biomass Upgrading

AbstractHydrazine‐oxidation‐assisted self‐powered H2 generation system greatly expands the applicability of hydrogen production technology. However, the high cost of hydrazine greatly impedes the widespread adoption of hydrazine‐contained energy systems for large‐scale H2 production. Besides, the gaseous products of hydrazine splitting, comprising a mixture of H2 and N2, necessitate energy‐intensive downstream separation. Here, taking advantage of a low‐potential furfural oxidation reaction (FOR) on the Cu electrode, a self‐powered H2 production system by integrating a direct furfural fuel cell (DFFC) and a bipolar H2 production electrolyser is reported. Ru‐dispersed Cu nanowire with remarkable catalytic activity is developed as a hydrogen evolution reaction (HER) catalyst to couple with the FOR. The HER‐FOR electrolyzer achieves bipolar H2 production with an apparent 200% Faradaic efficiency, attaining a current density of 100 mA cm−2 with a low cell voltage of 0.43 V. The DFFC displays an open circuit potential of 0.969 V and a peak power density up to 193 mW cm−2. Inspired by the bipolar H2 production that eliminates the gas separation, a self‐powered system utilizing furfural as the sole consumable, which yields a pure H2 production rate of 6 mmol h−1 m−2 is demonstrated. This work provides a new avenue for constructing self‐powered H2 production systems.

CO2 Electrolyzers.

CO2 electrolyzers have progressed rapidly in energy efficiency and catalyst selectivity toward valuable chemical feedstocks and fuels, such as syngas, ethylene, ethanol, and methane. However, each component within these complex systems influences the overall performance, and the further advances needed to realize commercialization will require an approach that considers the whole process, with the electrochemical cell at the center. Beyond the cell boundaries, the electrolyzer must integrate with upstream CO2 feeds and downstream separation processes in a way that minimizes overall product energy intensity and presents viable use cases. Here we begin by describing upstream CO2 sources, their energy intensities, and impurities. We then focus on the cell, the most common CO2 electrolyzer system architectures, and each component within these systems. We evaluate the energy savings and the feasibility of alternative approaches including integration with CO2 capture, direct conversion of flue gas and two-step conversion via carbon monoxide. We evaluate pathways that minimize downstream separations and produce concentrated streams compatible with existing sectors. Applying this comprehensive upstream-to-downstream approach, we highlight the most promising routes, and outlook, for electrochemical CO2 reduction.

Using isopropanol as the hydrogen donor to achieve by-product-free biological hydrogenation in water with carbonyl reductase

In this study, the reaction equilibrium was broken using isopropanol as a co-substrate, which was different from previous glucose as a co-substrate for furfural reduction, solving the problems of many by-products, low selectivity, and the addition of sodium phosphate buffers. The volatility of isopropanol and acetone prevented the production of by-products to the reaction system, improving the conversion and selectivity. 10 g/L furfural could be converted into furfuryl alcohol in pure water, and the furfural conversion was 90%, furfuryl alcohol selectivity was 100%, and the concentration of furfuryl alcohol could reach more than 20 g/L through accumulation reaction. No by-products were produced in this reaction system, and a single furfuryl alcohol product was obtained in the water catalytic system, which was convenient for downstream separation and purification. At the same time, based on the theory of the NADH coenzyme cycle system, this catalytic method could complete the conversion of various aldehydes into the corresponding alcohols, and it could be expanded to various biological hydrogenation projects, which has important industrial development and production prospects.

Bottom-up production of injectable itraconazole suspensions using membrane technology

Bottom-up production of active pharmaceutical ingredient (API) crystal suspensions offers advantages in surface property control and operational ease over top-down methods. However, downstream separation and concentration pose challenges. This proof-of-concept study explores membrane diafiltration as a comprehensive solution for downstream processing of API crystal suspensions produced via anti-solvent crystallization. It involves switching the residual solvent (N-methyl-2-pyrrolidone, NMP) with water, adjusting the excipient (d-α-Tocopherol polyethylene glycol 1000 succinate, TPGS) quantity, and enhancing API loading (solid concentration) in itraconazole crystal suspensions. NMP concentration was decreased from 9 wt% to below 0.05 wt% (in compliance with European Medicine Agency guidelines), while the TPGS concentration was decreased from 0.475 wt% to 0.07 wt%. This reduced the TPGS-to-itraconazole ratio from 1:2 to less than 1:50 and raised the itraconazole loading from 1 wt% to 35.6 wt%. Importantly, these changes did not adversely affect the itraconazole crystal stability in suspension. This study presents membrane diafiltration as a one-step solution to address downstream challenges in bottom-up API crystal suspension production. These findings contribute to optimizing pharmaceutical manufacturing processes and hold promise for advancing the development of long-acting API crystal suspensions via bottom-up production techniques at a commercial scale.