Bridging Liquid Research Articles

Modification of Ceritinib Crystal Morphology via Spherical Crystallization

The formulation process for some drugs can be challenging, due to their unfavorable physical and mechanical properties and poor water solubility. Powder technology has made a significant impact in regard to the modification of the particles in active pharmaceutical ingredients (APIs) to produce high-quality granules. Spherical particles are preferred over other shapes, due to their high tap and bulk density, reduced dustiness, better flowability, strong anti-caking properties, and better mechanical performance during tableting. The present study investigates the possibility of obtaining spherical crystals of ceritinib, a drug used for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer, which belongs to BCS class IV drugs and has a platy crystal structure. Ceritinib spheres were prepared by spherical agglomeration, in a ternary system, and quasi-emulsion solvent diffusion, with the addition of polyvinylpyrrolidone, as well as a combination of these two methods. With the combined method of spherical crystallization, crystals with the most favorable morphology and the narrowest distribution of particle sizes were obtained, which was the reason for further optimization. The influence of different impeller geometries and mixing rates on the morphology of the obtained crystals was examined and the optimal conditions for the process were selected. Using empirical correlations and a visual criterion, the process was scaled up from a 0.1 L to a 1 L batch crystallizer. The obtained crystals were characterized by light and scanning electron microscopy. The addition of a bridging liquid and/or a polymer additive did not change the internal structure of the ceritinib crystals, which was confirmed by X-ray powder diffraction.

SPHERICAL AGGLOMERATION OF TELMISARTAN - AN APPROACH TO IMPROVE PHYSICOCHEMICAL PROPERTIES

The study explains the preparation of spherical agglomerates (SA) of telmisartan (TLS), a BCS class II drug used to improve it’s physicochemical and bulk properties. Drugs of this class could potentially exhibit dissolution rate limited absorption. TLS spherical agglomerates were designed using hydrophilic polymer (PVP K-30), dimethyl formamide (DMF), water and ethyl acetate (bridging liquid) by solvent change method and evaluated for micromeritic properties. The SA were characterized by particle size determination, FTIR, PXRD and SEM. The results of micromeritic studies indicated that SA showed improved flow properties due to their spherical shape and bigger size. Absence of strong interaction at molecular level and alteration in the crystal structure of TLS with modification in crystallinity was confirmed by FTIR and PXRD respectively. TLS solubility characteristics were improved by this approach.

Spherical agglomeration kinetics: A mechanistic approach

Spherical agglomeration, a process of in-suspension particle size enlargement, can substantially improve critical quality attributes of powders. In this work, a paracetamol-heptane-water system is used to investigate the kinetics of spherical agglomeration, demonstrating for the first time the influence of true bridging liquid to solid ratio (TBSR) and suspension loading on the evolving size, shape and density of agglomerates. A critical range of TBSR is identified where robust agglomerates are formed that are round, moderately dense, and have a controlled size distribution. Immersion nucleation, drop breakage, and agglomerate densification by impact are the controlling rate processes. Increasing mixing intensity reduces agglomerate size, porosity and agglomeration time. Increasing solids loading increases agglomeration time while yielding smaller agglomerates with lower porosity. A first order consolidation model quantitatively predicts the agglomeration kinetics as well as agglomerate properties with increasing TBSR, and is a powerful tool for design and scale up.

Optimizing irbesartan spherical agglomerates through principal component analysis and experimental design

Background: This study explores the amalgamation of crystallization and agglomeration through spherical crystallization, aiming to develop the spherical crystals of Irbesartan with improved micromeritic properties. The main objective is to use spherical crystallization techniques to improve the micromeritic characteristics of Irbesartan, which has poor flow and compressibility because of its crystal habit. Methodology: A solvent change approach was utilized to synthesize spherical agglomerates of Irbesartan. Several system parameters, including the amount of bridging liquid, the rate of stirring, and the concentration of the polymer, were tuned to enhance the particle size distribution and mechanical qualities. SEM, GC, PXRD, DSC, and FTIR analyses characterised the spherical crystals. Result and Discussion: The study demonstrated that spherical crystallization significantly enhanced Irbesartan's micromeritic properties. The angle of repose of optimized agglomerates was reduced by around 52%, indicating improved considerably flowability of irbesartan. The sphericity of the crystals was validated by SEM examination (shape factor: 0.996), and the solvent levels were found to be within allowable bounds by GC analysis. PXRD data showed no polymorphism alterations, and DSC/FTIR analyses confirmed that the excipients and drug were compatible. Conclusion: This process provides a feasible alternative to classic granulation and agglomeration procedures, resulting in better flow, compressibility, and spherical crystals. It streamlines the Irbesartan formulation, improving efficiency and uniformity, reducing manufacturing costs, higher tablet consistency, and enhancing patient compliance.

Tailor-joining of Ti6Al4V skin with V-shaped assembly error using enhanced PLBW scheme: Keyhole dynamics and metal bridging behavior

Building thin-walled titanium alloy skin using conventional laser beam welding (LBW) frequently suffers from undesirable seam quality due to the V-shaped notch; a typical assembly error occurs after skin rolling with a specific sheet thickness range. This work proposed an improved scheme with metal bridging capacity and liquid film stability to overcome this by executing a pulsed laser beam and spot irradiation in a flat-top mode. Welding was performed on 1.5 mm-thick Ti6Al4V sheets configured in the butt joint with a reserved notch geometry, which is 20 degrees between the groove surface. We also conducted numerical modeling and solutions concerning the heat-flow-phase dynamics using an enhanced ray tracing algorithm. Results show that the as-build weld beads, characterized by middle rippers, slight depression, and edge ridges, present superb continuity and uniformity when applying an average heat input of 40–90 J/mm and a pulse energy of 187.5–750 J. Effective metal bridging across the notch error is achieved at both pulse duration and interval phases due to not only the complete melting of welding side but also the enhanced melt film stability against the surface tension. The cooling of the weld pool starts with a sharp temperature drop at ∼3×105 K/s (on average) during the keyhole collapsing regime, then slows down due to the damped up-down oscillation of the free surface combined with the natural convection-conduction effect. The flow pattern of molten metal changes from squeezing-like to vortexes and finally to a backfilling mode, depending on the evolution of keyhole geometry. Although the keyhole dynamics differs, various process conditions regarding heat input and pulse energy yield effective metal bridging of a single weld spot and sufficient refusion between the adjacent weld spots, ensuring the well-overlapped weld bead formation.

Cleaning of fine-grained lignite by two-stage hydrophobic flocculation using different waste oils

ABSTRACT In this study, the conditions for obtaining clean coal from fine-grained lignite suspensions by two-stage hydrophobic flocculation using different waste oils were investigated. Waste vegetable oil, waste hydraulic oil and waste engine oil were chosen as bridging liquids for hydrophobic flocculation tests. During the studies, sodium silicate was used as the dispersant. Acetone was used at each stage to clean the floc obtained from the agglomeration process. The ash content (%) and combustible recoveries (CR, %) of the floc obtained at the end of each experiment were determined. In addition, contact angle (θ) and calorific values (kcal/kg) were measured and the results were evaluated in detail. At the end of the cleaning stages, low ash clean coal was obtained with a very high combustible recovery. In addition, it was observed that the calorific values increased considerably from 5128 to 5772,5558 to 6304 and 5447 to 5732 using waste vegetable oil, waste hydraulic oil and waste engine oil, respectively.

Integrated Continuous Process Design for Crystallisation, Spherical Agglomeration, and Filtration of Lovastatin

PurposeThis work seeks to improve the particle processability of needle-like lovastatin crystals and develop a small-footprint continuous MicroFactory for its production.MethodsGeneral conditions for optimal spherical agglomeration of lovastatin crystals and subsequent product isolation are developed, first as batch processes, and then transferred to continuous MicroFactory operation.ResultsMethyl isobutyl ketone is a suitable bridging liquid for the spherical agglomeration of lovastatin. Practical challenges including coupling unit operations and solvent systems; mismatched flow rates and inconsistent suspension solid loading were resolved. The successful continuous production of lovastatin spherical agglomerates (D50 = 336 µm) was achieved. Spherical agglomeration increased the density of the bulk lovastatin powder and improved product flowability from poor to good, whilst maintaining lovastatin tablet performance.ConclusionA continuous, integrated MicroFactory for the crystallisation, spherical agglomeration, and filtration of lovastatin is presented with improved product particle processability. Up to 16,800 doses of lovastatin (60 mg) can be produced per day using a footprint of 23 m2.

Oil Agglomeration in Zonguldak Bituminous Coal Dust: The Role of Inorganic Materials

In the present study, the effect of various The oil agglomeration method is of great importance for high recovery and low cost in capitalizing our energy resources that create environmental problems due to fineness of particle size or our low quality, oxidized coal resources with large reserves. Inorganic pretreatment materials, the ratio of bridging liquid, agglomeration time and mixing speed on the agglomeration recovery in the beneficiation of Zonguldak coal with low ash content (2.23%) through oil agglomeration. In the experiments, kerosene was used as the bridging liquid and NaCl, FeCl2, Fe2(SO4)3, Al2(SO4)3 were used as inorganic pretreatment materials. In the agglomeration experiments in which inorganic pretreatment materials and kerosene were used together, the maximum recovery was determined in the condition where the kerosene concentration was 15%, the mixing speed was 800 rpm and the agglomeration time was 10 min. It was found that, the recovery under suitable conditions was 71.5% in the agglomeration experiments conducted with only kerosene, whereas it was in varying rates between 76.5% and 81.6% in experiments where pretreatment materials and kerosene were used together. Among the inorganic pretreatment materials, when used together with kerosene, the best recovery was obtained with the use of 50 mg/L Fe2(SO4)3. The agglomeration recovery obtained in the experiments conducted with only kerosene under optimum conditions was reached when the agglomeration time was 5 min in the experiments in which the inorganic pretreatment materials and kerosene were used together.

The use of petroleum derivative mixtures as bridging liquid for oil agglomeration of lignite coal

ABSTRACT The aim of the present study was to investigate the use of mixtures of petroleum derivatives as bridging liquids for oil agglomeration of Sivas/Gemerek lignite coal. The study investigated the effect of various physical process parameters, such as type and dosage of bridging liquid, pulp pH, pulp density, agglomeration time, and coal particle size. Oil agglomeration experiments were evaluated along with yield, organic matter recovery and ash rejection values. The optimum conditions for agglomeration were found as follows: adding engine oil (0w-30) as a bridging liquid at a dosage of 30%, maintaining a pulp pH of 2, using a pulp density of 3.6% w/w, agglomerating for 25 minutes, and using coal particles with a size of −500 µm. Under these optimum oil agglomeration conditions, a yield of 85.4%, an organic matter recovery of 94.1% and an ash rejection of 51.6% were obtained. Under the optimum oil agglomeration conditions achieved, the ash content of the Sivas/Gemerek lignite coal was reduced from 19.1% to 15.5% level.

OPTIMIZATION AND CHARACTERIZATION OF FAST DISSOLVING TABLETS OF CANDESARTAN CILEXETIL PREPARED FROM SPHERICAL AGGLOMERATES

The primary objective of this study was to develop a rapidly dissolving tablet containing an antihypertensive drug, candesartan cilexetil (CAND). The research work focused on improving solubility and in vitro dissolution of drugs using spherical agglomeration technique. Spherical agglomerates of CAND were developed using PVPK-30 as polymer and dichloromethane as bridging liquid. A spherical agglomerate of CAND was used to formulate fast dissolving tablet (FDT) with different superdisintegrants like Crospovidone and Cross carmellose sodium. The prepared powder blend was evaluated for different pre-compression parameters like solubility, compressibility index, Hausner’s ratio and flow property and post-compression parameters including in vitro dissolution study. The solubility of prepared agglomerates was found to be 0.15 to 0.91 mg mL-1, and it was higher than the pure drug (0.00071 mg mL-1). In vitro drug release study of optimized batch of FDT has shown 95.47 % of drug release. From the results, it was revealed that the prepared FDT using the agglomeration technique might be used to enhance the solubility and bioavailability of CAND to augment acute and chronic hypertension therapy.

Precise particle size control during spherical agglomeration of benzoic acid by modification of the bridging liquid phase using TWEEN 20

The interest in spherical agglomeration processes in the pharmaceutical industry is rising due to the possibility of direct tableting of Active Pharmaceutical Ingredients and enhancements in bulk powder properties translating into improved powder processability. While agglomerating needle-shaped particles into spheres offers numerous advantages, such as improved flowability, filterability, and particle density, achieving precise control over the particle size and shape of the agglomerates remains a significant challenge. More specifically, the obtained agglomerate size rarely reaches values below 500 μm, which is the desired size range for pharmaceutical applications. To address this challenge, the current research investigates the effectiveness of incorporating surfactants at varying concentrations as a means to control the particle size and shape of the resulting agglomerates. Reversed addition antisolvent crystallization experiments were performed in ethanol/water using benzoic acid as a model compound, followed by the addition of a bridging liquid (toluene), which wets and bridges the single crystals into agglomerates. To modify the interfacial tension between the two immiscible liquid phases, different concentrations of the tween 20 surfactant were used, leading to a range of interfacial tensions spanning from 0.50 to 16.38 × 10−3 N/m. Both crystallization and agglomeration processes were monitored in situ using in-process microscopy tools. The experimental results demonstrated that by adjusting the surfactant concentration and thus the corresponding interfacial tension of the bridging liquid, highly tunable agglomerate sizes were achieved, ranging from 160 μm to 4412 μm. A higher surfactant concentration is correlated with smaller agglomerates and is key to control the final agglomerate size. However, it should be noted that the introduction of surfactants in the spherical agglomeration process negatively impacted the agglomerate's strength. Nonetheless, this method remains a promising and innovative technique for controlling the final particle size during spherical agglomeration.

Design of spherical agglomeration via salt-induced liquid–liquid phase separation

In this study, a novel strategy for spherical agglomeration via salt-induced liquid–liquid phase separation (SI–SA) was developed. SI–SA technology achieves phase separation in the miscible binary anti-solvent crystallization system by adding certain amounts of salts, avoiding the use of toxic bridging liquids. Water–organic solvent–salt systems that induced phase separation were selected using phase separation experiments. The wetting performance of the organic solvent was estimated by droplet experiments, and organic solvents with stronger wettability for crystals than water would be selected for further verification. Spherical agglomeration experiments were designed based on the ternary phase diagrams of these selected systems. Water–organic solvent–salt systems of benzoic acid were selected, starting with six organic solvents and four salts. A total number of 16 water–organic solvents–salt systems were effectively predicted using the SI–SA strategy. The in-situ process analysis tool indicated that the formation of spherical particles of benzoic acid underwent a process of crystallization, phase separation, wetting, two-step agglomeration, and consolidation. The stirring rate and mass ratio of salt to final crystals were found to be important for controlling the morphology and particle size of the spherical crystals. The spherical particles of aspirin and salicylic acid were successfully predicted in different systems via SI–SA technology, demonstrating the universality and potential usage of SI–SA technology in industry.

ENRICHMENT OF SİVAS/GEMEREK LIGNITE COAL BY OIL AGGLOMERATION USING DIFFERENT VEGETABLE OILS

The aim of this study was to investigate the use of various vegetable oils (almond oil, hazelnut oil, poppy oil, soybean (soya) oil, sunflower oil) for Sivas/Gemerek (in Turkey) lignite coal by oil agglomeration. The study examined the effect of bridging liquid type and dosage on oil agglomeration. Vegetable oil dosages of 2%, 5%, 10% and 20% were investigated in oil agglomeration experiments. The agglomeration of lignite coal with these bridging liquids was evaluated based on yield, combustible recovery and ash rejection. The agglomeration performances of these vegetable oils were compared. The highest ash rejection (70.30%) was observed by using soybean (soya) at 20% of the bridging liquid dosage. The yield and combustible recovery of lignite coal were achieved 36.46% yield and 38.05% combustible recovery in this soybean (soya) oil dosage, respectively. The lignite coal ash content was reduced from 19.08% to 15.54% under these optimum conditions.

True bridging liquid-solid ratio (TBSR): Redefining a critical process parameter in spherical agglomeration

Spherical agglomeration of crystals via addition of an immiscible bridging liquid can improve active pharmaceutical ingredient handling and tabletability. Bridging liquid amount is quantified by the bridging liquid-solid ratio (BSR). However, the optimal range of the BSR for agglomerates to form is highly dependent on the bridging liquid/solvent/antisolvent system. Here, a new definition is introduced to account for bridging liquid-solvent miscibility; true bridging liquid-solid ratio (TBSR). A method for calculating TBSR from the system ternary phase diagram is demonstrated for five different common binder liquids with acetone/water as the solvent/antisolvent system. Results show the value of BSR varies dramatically for a given TBSR as a function of both the system and the solids loading. Experimental salicylic acid agglomeration studies confirm optimal BSR varied widely with binder liquid and solids loading between 0.2 and 2, but the optimum TBSR for all experiments was in a narrow range between 0.05 and 0.15. Thus, TBSR is a robust dimensionless parameter for design and scale up of spherical agglomeration processes.

Nicotinamide-based agglomerates of ibuprofen: formulation, solid state characterization and evaluation of tableting performance with in-silico investigation

BackgroundThe objective of the present investigation was to obtain directly compressible agglomerates of ibuprofen with nicotinamide by a quasi-emulsification solvent diffusion technique. Ibuprofen-nicotinamide agglomerates were prepared by quasi-emulsification solvent diffusion technique using ethanol (good solvent), water (poor solvent), and chloroform (bridging liquid). The prepared agglomerates were characterized by ATR-FTIR, powder X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy and were evaluated for tableting performance and in vitro drug release. To appropriately identify the hydrogen bonding sites, a thorough understanding of the structures of API and coformer is necessary, hence molecular docking approach was implemented to depict the interaction between the proposed coformer and COX-2 protein (PDB Id:4PH9).ResultsThe percent yield of agglomerates was in the range of 85–98 w/w%, and drug content for all batches was in the range of 96–99%. The microphotographs showed irregular circularly shaped agglomerates. ATR-FTIR study showed a strong possibility of hydrogen bonding between ibuprofen and nicotinamide. The crystallinity of ibuprofen was slightly reduced and confirmed by P-XRD and DSC. Crushing strength and friability studies showed good handling qualities of ibuprofen agglomerates. Heckel plot studies showed low mean yield pressure and high tensile strength, indicating excellent compressibility and compactibility of ibuprofen agglomerates. More than 90% drug release was obtained within 60 min in PBS (pH 7.4). The docking studies revealed that nicotinamide individually has –CDOCKER energy 16.8109 where coformer showed 29.0584, which indicates coformer has a better binding affinity to target as compared to nicotinamide individual.ConclusionsIt can be concluded that the agglomerates improved the dissolution, tableting performance, and solid-state properties of ibuprofen and hence can be useful to improve the therapeutic performance of ibuprofen.Graphic

Effect of Different Stabilizers on Spherical Agglomerates of Montelukast Sodium by Quasi Emulsion Solvent Diffusion (QESD)

Abstract: The present study was focused on the spherical crystallization of an asthmatic drug, Montelukast Sodium (MLS) using quasi emulsion solvent diffusion (QESD) technique in which distilled water was an external phase and the internal phase consisted of Ethanol which acts as good solvent and Ethyl acetate as a bridging liquid for recrystallization and agglomeration process. Apart from being poorly water soluble, MLS exhibits poor flow and compressibility. The spherical agglomeration was carried out in the presence of different stabilizers like acacia, PEG 4000, sodium lauryl sulphate, span 40 and tween 80. The prepared agglomerates were characterized in terms of production yield, drug content, solubility, in-vitro release profile, Xray diffraction (XRD), and Fourier transform infra red spectroscopy (FT-IR).The optimized spherical agglomerates exhibited excellent physicochemical and micromeritic properties, solubility and dissolution rate when compared with pure drug .The XRD also revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate. FTIR study reveals there are no chemical changes in prepared recrystallized agglomerates. The considerable improvement in the dissolution rate of MLS from optimized crystal formulation was attributed to the wetting effect of polymers, decreased drug crystallinity, altered surface morphology and micronization. If this process can be scaled-up to manufacturing level, this technology has the potential to provide the directly compressed spherical agglomerates with improving the physicochemical and micromeritic properties

ONE POT DEVELOPMENT OF LIPID-BASED QUERCETIN SPHERICAL AGGLOMERATES FOR BIOAVAILABILITY ENHANCEMENT: IN VITRO AND IN VIVO ASSESSMENTS

Objective: Quercetin, a wonder flavanoid despite numerous pharmacological actions, has limited clinical applications due to solubility and permeability issues and additionally having shorter biological half-life. The goal of the current work was to design Quercetin lipid-based spherical crystals, to improve its oral bioavailability and sustain its in vivo plasma levels. Methods: An anti-solvent precipitation method was employed to prepare quercetin spherical agglomerates using ethanol and distilled water as good and bad solvents, respectively. As bridging liquid chloroform, dichloromethane, hexane and gelucire 43/01, compritol 888 as lipid carrier were screened. The drug-to-lipid polymer proportion and stirring speed effect were optimized by 3-level, 2-factor, experimental design. Numerical optimization function was employed to identify the optimum level of independent variables. Spectroscopic, micromeritic, surface morphology, size distribution, saturated solubility, in vitro dissolution, in vivo pharmackokinetic and stability studies were performed. Results: Surface morphology studies indicated the agglomeration of quercetin needle-like fragments into a spherical shape, which further showed smooth surfaces due to entrapment of QC in lipid carrier. The spherical agglomerates of quercetin showed a four-fold improvement in aqueous solubility compared to pure drug and showed 92.13% release in 8 h. The optimised formulation showed a 3.69-fold enhancement in relative bioavailability in contrast to the marketed preparation in an in vivo pharmacokinetic analysis in male Wistar rats. Conclusion: The obtained lipid-based spherical crystals of quercetin with enhanced bioavailability could be effectively used for its various potential pharmacological applications. The designed system can also be utilized to deliver other phytochemicals with poor bioavailability due to limited solubility and permeability.

Crystallo-co-Agglomeration Technique for Improving Physicochemical Properties, Compressibility and Solubility Characteristics of Metronidazole

The objective of this study is to develop crystallo-co-agglomeratesof metronidazole having improved physicochemical, compressibility andsolubility properties. The process of agglomeration employed the use ofdichloromethane (good solvent), ethanol (bridging liquid) and distilled water (poorsolvent). Micromeritic properties of the metronidazole co-agglomerates werestudied in terms of bulk density, tapped density, Carr's index, Hausner’sratio, and angle of repose. Co-agglomerates were also subjected to compactionstudies using the Heckel and Kawakita compaction models. Characterisation ofthe agglomerates was studied using Scanning electronic microscopy, Fourier-transformed infrared spectroscopy, and X-ray diffraction. The co-agglomerateswere further evaluated for drug release profile. The micrometric properties anddissolution characteristics of metronidazole co-agglomerates were significantlyimproved when compared to pure metronidazole. The angle of repose formetronidazole co-agglomerates was found to be 29.77°±1.09, Carr’s index was13.60±0.35, and Hausner’s ratio was 1.15±0.06, indicating good flow ability. Thedrug released over a period of 30 min was 102.61%, this shows better drugrelease than the pure drug, this could be due to the solubilization of the drug inpresence of hydrophilic polymers. It can be concludedthat metronidazole was successfully prepared using the crystallo-co-agglomeration technique with improved micrometric properties, excellentcompressibility, and improved solubility characteristics.

Spherical crystal agglomeration technique for improved flow properties and oral bioavailability of atazanavir sulphate.

Aim: The current research focused on formulation of spherical crystal agglomerates (SCA) of atazanavir sulphatefor improving flow property and solubility. Materials & methods: SCA were formulated by quasi-emulsification solvent diffusion. Methanol, water and dichloromethane were employed as a good solvent, bad solvent and bridging liquid respectively. Results & conclusion: SCA with improved solubility and micromeritic properties were directly compressed into a tablet. The SCA tablets had higher dissolution rates compared with plain drug and marketed product. Invivo pharmacokinetic studies revealed higher Cmax and AUC0-t of the SCA than marketed product with relative bioavailability of 1.74. The formulation was stable for more than 3months, with insignificant difference in % drug content and % drug dissolution.

Improved Spherical Particle Preparation of Ceftriaxone Sodium via Membrane-Assisted Spherical Crystallization

Spherical drug particles prepared by the spherical crystallization technique can simultaneously improve the mobility of particles, mechanical properties, drug solubility and bioavailability, etc. However, high-efficient mixing of a solution and the formation of uniform bridging liquid droplets were crucial for accurate control of spherical crystallization processes. Herein, a novel membrane-assisted spherical crystallization (MASC) technology was proposed to produce monodisperse spherical agglomerates of ceftriaxone sodium. The poor solvent permeation rate of MASC was stabilized by adjusting the liquid flow velocity in the shell side and tube side. Uniform bridging liquid droplets constructed by a polytetrafluoroethylene hollow fiber membrane were observed in real time. A stable flow field and crystallization microenvironment were provided on the hollow fiber membrane surface. The crystal size distribution and the coefficient of variation of ceftriaxone sodium products were improved compared with those of conventional spherical crystallization (CSC) under the same stirring rate. The impurities of CSC products did not meet the requirements due to the degradation after 14 days’ acceleration experiment, while the one of MASC products still met the pharmacopoeia requirements after 30 days. This study provides a potential membrane-based technology for the enhancement of spherical crystallization of related drugs.