Bridging Liquid Research Articles

Design and mechanism of agglomeration of aspirin crystals in pure solvents

Agglomeration with improved flowability for platy crystals is desirable in pharmaceutical downstream processing. The formation of agglomerates in pure solvents without the aid of bridging liquids is a convenient and low-cost method compared with complex spherical crystallization. In this work, the adhesion free energies between aspirin crystals in six solvents were calculated using Lifshitz-van der Waals acid-base theory to screen suitable solvents for agglomeration. The maximum stirring rate for agglomeration was determined by adhesion forces and dispersion forces. Then the agglomerates of plate-shaped aspirin were successfully prepared in acetone, methanol, ethanol, 2-propanol, and ethylene glycol without additives by simple cooling crystallization. The interactions between solvent and crystal surfaces were also used to explain the outcomes. A feasible mechanism for the agglomeration process of platy crystals was elucidated, involving the adhesion of dominant crystal facets at the beginning. The effect of stirring rate, cooling rate, and initial supersaturation on agglomeration degree and particle size of aspirin agglomerates were studied. The obtained aspirin agglomerates under the optimal conditions exhibited a uniform particle size distribution, a high agglomeration degree, and superior flowability.

Processability and Oral Bioavailability Improvement of Itraconazole by Particle Engineering Technique.

The current study aimed to improve the processability and oral bioavailability of itraconazole (ITZ) via spherical agglomeration. ITZ-spherical agglomerates (ITZ-SA) and ITZ-poloxamer 407-spherical agglomerates (ITZ-PLX-SA) were optimized using Box-Behnken design. Here, the drug release was affected by polymer concentration and stirring speed, whereas particle size was altered by stirring speed, polymer concentration, and amount of bridging liquid. Heckel and Kawakita studies showed a reduction in mean yield pressure and remarkably lowered 1/b value than ITZ, indicating better compactibility and flowability of ITZ-PLX-SA. Physicochemical interactions were not observed during the process, as indicated by ATR-FTIR, DSC, and XRPD. The significant improvement in % drug release of ITZ-PLX-SA was attributed to better wettability and the presence of polymer than ITZ-SA and ITZ. The pharmacokinetic study in rats indicated fivefold enhanced Cmax and twofold improved AUC for ITZ-PLX-SA than plain drug. Thus, spherical agglomeration could improve overall processability and pharmacokinetic profile of ITZ.

PARTICLE DESIGN OF KETOCONAZOLE BY SPHERICAL CRYSTALLIZATION

Objective: This research aimed to make ketoconazole spherical crystals to improve the micromeritic properties and the dissolution rate using the solvent change method.
 Methods: The solvent that is used in the process of spherical crystallization consists of three types: ether (good solvent), distilled water (bad solvent), and n-hexane (bridging liquid), with a 20:70:10 ratio each. The agglomerates were characterized by differential scanning calorimetry (DSC, powder X-ray diffraction (XRPD), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM).
 Results: Based on PXRD, DSC, and FTIR spectrophotometer results, it was determined that there was no internal change of ketoconazole crystalline structure during the recrystallization process into spherical crystals, and SEM results revealed that the morphology of the crystal became spherical. Based on the micromeritic properties evaluation results, it was concluded that the ketoconazole spherical crystals have superior micromeritic properties than the conventional ketoconazole. The dissolution test results showed an enhancement in the dissolution rate of spherical crystals compared with the untreated ketoconazole.
 Conclusion: Thus, spherical crystals of ketoconazole appear to be a viable approach for enhancing solubility characteristics and micromeritic properties, which would be highly advantageous for processing ketoconazole as a high-dose drug.

Agglomeration–Flotation of Microplastics Using Kerosene as Bridging Liquid for Particle Size Enlargement

Microplastics (MPs), defined as plastics with diameters between 1 and 5000 µm, are problematic pollutants in the environment, but their removal is challenging because of their minute size. One promising approach for their removal is flotation because MPs are inherently hydrophobic. However, the very small particle size of MPs lowers the probability of MPs-bubble collision and attachment that in turn affects the efficiency of the process. To address this challenge, we propose the use of agglomeration-flotation, a technique using kerosene as a bridging liquid to enlarge the particle sizes of MPs and make them amenable to flotation. In this study, the effects of kerosene dosage on particle size enlargement and floatability of six types of MPs with 100–1000 µm size fractions were investigated. The results showed that MPs with lower density compared with water could easily float in water without bubble attachment and particle agglomeration required. So, the effects of agglomeration on removal were negligible. In contrast, agglomeration using kerosene enhanced the floatability of MPs with high-density plastics. Moreover, image analysis was used to determine the agglomerated MPs’ particle size. The results indicate that kerosene could agglomerate the MPs and enhanced the removal of MPs by agglomeration-flotation.

Design of spherical agglomerates via crystallization with a non-toxic bridging liquid: From mechanism to application

The cooling crystallization-spherical agglomeration (CCSA) technology proposed in this work overcomes the disadvantages of complex process and biohazardous solvents, which has broad application prospects in green and efficient granulation. CCSA selects oleic acid as a novel green and effective bridging liquid, and the results of droplet experiment and molecular simulation indicate that oleic acid presents the best wetting performance compared with the reported bridging liquids. Mechanistic studies demonstrate that oleic acid can induce spherical agglomeration during crystallization in a single solvent system, especially in water, reducing the dosage of organic solvent by about 90%, and fundamentally eliminating the toxicity of bridging liquid. The volume ratio of bridging liquid to solvent (RBS) and agitation are emphasized as the critical parameters tuning the particle size and sphericity. Further, the spherical agglomerates of benzoic acid, L-leucine and aspirin with controllable size and high sphericity were successfully prepared, which verifies the universality of CCSA.

Formulation and optimization of polymeric agglomerates of Bosentan monohydrate by crystallo-co-agglomeration technique

BackgroundThe polymeric spherical agglomerate of Bosentan monohydrate was prepared by crystallo-co-agglomeration technique, for enhancing the micrometric properties and solubility of the drug. The agglomerates were developed using two distinct solvents, DCM as a good solvent and bridging liquid and water as a weak solvent, respectively. Hydrophilic polymer like HPMC K100M is used as a hardening agent which gives mechanical strength to the agglomerates, and PEG6000 is used as a wetting agent. Other excipients like talc which was used as a size enhancer, and PVA was used as an emulsifier agent. The formulation was optimized by Box–Behnken design. The concentration of talc and PEG6000, as well as rotation speed, was considered as independent variables. The particle size, angle of repose, and % drug content were used as dependent variables to investigate the effect of independent variables on dependent variables. The spherical crystal agglomerates were subjected to various physicochemical evaluations.ResultsThe results revealed that as the concentration of talc and PEG6000 increases, the sphericity and particle size of the agglomerates increase, and at a low agitation, speed agglomerates become more spherical and coarser, which is confirmed by FESEM. The characterization like FTIR confirms no interaction with excipients, while XRPD confirms the polymorphic changes, and gas chromatography (GC) confirms the concentration of residual organic solvents in PDE limits. The optimized formulation of SAs showed a good angle of repose which is 30.33 ± 0.35, and the % cumulative drug release at 20 min was 94.14 ± 0.628%. Finally, the FDTs of the optimized batch were prepared.ConclusionsThe comparison of the in vitro release study of pure drugs with agglomerates and fast dispersible tablets of agglomerates confirms the solubility improvement. Finally, it can be concluded that the polymorphic crystal agglomerates enhance the solubility and micrometric properties of Bosentan monohydrate.

Improvement of low-quality fine coal by ultrasonic hydrophobic flocculation

ABSTRACT In this study, the effect of ultrasonic pretreatment on hydrophobic flocculation of fine coal was investigated and named as ultrasonic hydrophobic flocculation (USHF) technique. First, it was found that the ultrasonic power of 150 W and the ultrasonic pretreatment time of 180 sec was required to achieve for more combustible and good-quality coal. Then, the effects of ultrasound on the hydrophobic flocculation of coal with kerosene as bridging liquid were investigated and optimum kerosene concentration value was obtained 4 g/dm3 under the experimental conditions. Also, it was found that a stirring speed of 750 rpm was sufficient to achieve the maximum combustible recovery and minimum ash content values of fine coal particles. The effects of sodium silicate, sodium hexametaphosphate, and sodium pyrophosphate used as inorganic dispersants on the ultrasonic hydrophobic flocculation of coal were also studied. Sodium silicate was more effective than other dispersants in the presence of kerosene. Thus, it was concluded that the ultrasonic pretreatment is an effective method for the beneficiation of fine particle coal. Coal with an ash content of 17.63% was enriched and clean coal was recovered with an ash content of 9.75% with the efficiency of 94.35% by ultrasonic hydrophobic flocculation technique.

Demineralization of high ash coal fines of Indian origin using Mahua oil

The cost of oil is perhaps the biggest prohibitive aspect of the oil agglomeration process. Furthermore, the high ash low grade coals of India are more difficult to demineralize owing to their unfavourable hydrophilic surface chemistry. The objective of our present study is to use an indigenous and underutilized oil derived from Mahua seeds as a potential bridging liquid for oil agglomeration of low grade coal from Kaniha (Odisha, India) with 35% ash. Based on experimental results, Mahua oil demonstrably proved efficient in demineralization by 45–50% at lower oil concentrations (10–15 wt%), devoid of surfactants. Wet grinding of the coal using a vibratory cup mill was an essential pre-treatment step. A detailed investigation of all the crucial process parameters was performed through variation of pH, oil dosages, solid to liquid ratio and agitation conditions. The results obtained were further validated by detailed characterization of both raw and clean coal using zeta potential, FTIR, SEM studies and petrography. FTIR and petrographic studies validated the inherent and surface hydrophilicity of Kaniha coal. Zeta potential studies clearly showed an increase in surface potential around neutral pΗ which was found to be optimum for oil agglomeration. SEM results conclusively supported the formation of porous large size agglomerates. To our knowledge, ours is the first thorough examination of agglomeration potential of Mahua oil, which is an industrially underutilized product, thus supporting the aim of waste utilization and cleaner fuel production. • Crude Mahua oil as bridging liquid for oil agglomeration of high ash low grade Indian coal (35% ash) has been investigated. • Lower dosage (15 wt%) of oil under neutral conditions gave satisfactory results. • Wet grinding in a vibratory cup mill has been implicated to be a crucial pre-treatment step. • Demineralization by 45–50% was observed. • No pre-conditioning step of surfactant was included.

Enhancing Thermal Transport in Silicone Composites via Bridging Liquid Metal Fillers with Reactive Metal Co-Fillers and Matrix Viscosity Tuning.

Polymer matrix composites containing room temperature liquid metal (LM) microdroplets offer a unique set of thermo-mechanical characteristics that makes them attractive candidates for high performance thermal interface materials. However, to achieve the desired level of the composite thermal conductivity, effective bridging of such fillers into interconnected percolation networks needs to be induced. Thermal percolation of the LM microdroplets requires two physical barriers to be overcome. First, the LM microdroplets must directly contact each other through the polymer matrix. Second, the native oxide shell on the LM microdroplet must also be ruptured. In this work, we demonstrate that both physical barriers can be penetrated to induce ample bridging of the LM microdroplets and thereby achieve higher thermal conductivity composites. We accomplish this through a synergistic combination of solid silver and LM fillers, tuning of the silicone oil "matrix" viscosity, and sample compression. We selected silver as the solid additive because it rapidly alloys with gallium to form microscale needles that could act as additional paths that aid in connecting the LM droplets. We systematically explore the impact of the composition (filler type, volume fraction, and matrix oil viscosity) and applied pressure on the thermal conductivity and multiscale structure of these composites. We reveal the microscopic mechanism underlying the macroscopic experimental trends and also identify an optimal composition of the multiphase Ag-LM-Silicone oil composite for thermal applications. The identified design knobs offer path for developing tunable LM-based polymer composites for microelectronics cooling, biomedical applications, and flexible electronics.

Demineralization of high ash non-coking coal fines of Indian origin using Castor oil: Implications of wet milling

ABSTRACT The high-ash low-grade coals of Indian origin are relatively more challenging to demineralize due to their unfavorable hydrophilic surface chemistry. Herein, we report castor oil as a potential bridging liquid, which efficiently agglomerated high-ash low-grade coals by 55–60% at lower concentration (10 wt%) compared to literature (20–25 wt%), without inclusion of surfactants. A blend of castor oil and turpentine oil proved further beneficial. Wet milling of coal was a crucial prerequisite for efficient agglomeration. Three low-grade coals, Bhubaneshwari (35.8% ash), Kaniha (35% ash), and Hingula (26% ash), were beneficiated in the present study. A detailed analysis of process parameters validated with structural characterization using FTIR, Petrography, zeta potential, and SEM analysis was performed. The chemistry between ricinoleic acid in castor oil with that of surface functionality of coal is speculated to be the reason behind the obtained agglomeration results. Castor oil, being non-edible, bio-based, non-toxic, and non-polluting in nature, provides a greener alternative to mineral oils toward the production of clean fuel.

Effect of polymers and process parameters in augmenting the compactability and dissolution behaviour of oxcarbazepine spherical agglomerates

The hypothesis for the present work is proposed to explore the spherical crystallization technique for improving the micromeritics, compactability, and solubility characteristics of oxcarbazepine (OXZ), an anticonvulsant drug. Agglomerates containing different polymers (PEG 6000 and PVP K30) and process parameters were investigated for the enhancement of overall physicochemical performance and dissolution. Water, dichloromethane, and chloroform were used as a poor solvent, good solvent, and bridging liquid, respectively. Pure OXZ and spherical agglomerates were characterized for several properties including Fourier transformation-infrared spectroscopy, Differential scanning calorimetry, Scanning electronic microscopy, X-ray powder diffraction analysis, micromeritics, solubility studies, and in-vitro drug release kinetics. From the results, a considerable improvement in drug solubility and micromeritics of agglomerates than pure OXZ was observed. Compressibility parameters assessed from the Heckel plot showed agglomerates with a polymer having a higher value of slope (k) and less MyP is accountable for plastic deformation in agglomerates. Prepared spherical agglomerates showed an enhancement in solubility and rate of dissolution, which might improve their bioavailability.

Development of piroxicam mini-tablets enabled by spherical cocrystallization.

We examined the potential of the spherical cocrystallization (SCC) technology in simultaneously enhancing tablet manufacturability and dissolution of poorly soluble drugs by developing a mini-tablet formulation of piroxicam. The manufacturing of mini-tablets using a direct compression (DC) process is more challenging than conventional tablets because of the much stricter requirement on the micromeritic properties of formulated powders. The SCC process in this work involved two steps: 1) preparing a new piroxicam-ferulic acid (PRX-FA) cocrystal, and 2) forming spherical agglomerates with the aid of a suitable bridging liquid. The PRX-FA cocrystal exhibited enhanced solubility as well as improved plasticity. The bridging liquid, a mixture of chloroform and ethyl acetate (EA) (1: 2, v/v), was chosen based on the high computed adsorption energy of chloroform and EA on morphologically dominating crystal faces of PRX-FA. The improved flowability, tabletability, and dissolution rate of spherical PRX-FA enabled the successful development of a DC mini-tablet formulation with a high PRX loading (41wt%). This example shows that SCC is a powerful enabling technology for DC tablet formulation development of challenging drugs.

Kinetic Analysis for Agglomeration-Flotation of Finely Ground Chalcopyrite: Comparison of First Order Kinetic Model and Experimental Results

Particle size-flotation rate relationships can be discussed by a first-order kinetic model for flotation, which considers the probability of particle-bubble collision, attachment and detachment; and it was confirmed that recovery rate of finely ground hydrophobic particles in the froths are very low because of the limited particle-bubble collision probabilities. One method to improve the flotation of fine minerals is to agglomerate them before flotation using oil as a bridging liquid, an approached that has been shown to improve the flotation rates dramatically. A mathematical kinetic model for the flotation of agglomerated particles would be useful to design and optimize the agglomeration-flotation process, but no generally applicable model has been established yet. In this paper, flotation experiments of finely ground chalcopyrite were carried out with and without oil-agglomeration as pretreatment and the kinetic data (time-recovery curves) were compared with the conventional first-order kinetic model for flotation. Without agglomeration, time-recovery curves determined by the experiments fitted well with the model calculations, but there were significant deviations between experimental results and model calculations for the agglomerated particles; that is, experimental flotation recoveries were much higher than those calculated by the model. The conventional first-order kinetic model does not consider particle size changes during flotation while the experimental results suggested that the size of agglomerates increased in the flotation cell. This may be one of the reasons why significant deviations between the experimental and modelling results were observed, suggesting that the kinetic model for agglomeration-flotation need to consider the growth of agglomerates during flotation.

Detachment in capillary adhesion: the relative roles of tilting and separation

Abstract We study the dynamics of detachment in 2D capillary adhesion by considering a plate that is initially attached to a flat, rigid substrate via the surface tension of a bridging liquid droplet. In particular, we focus on the effect of allowing the plate to tilt freely during its subsequent motion. A linear stability analysis shows that small perturbations from equilibrium decouple into two modes: one in which the plate separates from the substrate, remaining parallel, and another in which it tilts, simultaneously causing the bridging droplet to migrate. If the initial tilt perturbation is of a similar magnitude to (or bigger than) the separation perturbation, then the presence of this second tilting mode can significantly alter the dynamics. Indeed, this tilting mechanism changes the ultimate fate of the plate: depending on the size of the plate and the initial perturbation, the plate may anomalously detach. We discuss this observation in relation to previous experiments on a 3D system that showed a qualitatively similar anomalous detachment.

Turpentine oil: a novel and natural bridging liquid for agglomeration of coal fines of high ash coals

ABSTRACT Oil agglomeration is an effective way to demineralize high ash coals as compared to froth flotation and density gradient separation. In this process, the choice of bridging liquid is critical with respect to economics and efficiency. Herein, we report turpentine oil as a potential bridging liquid which is demonstrably efficient in coal demineralization at lower concentration (10 vol.%) compared to literature (20–25 vol.%) without inclusion of surfactants, which enhances economic viability. We chose two high ash coals of Indian origin, with 26% and 34% ash. A varied range of particle sizes were examined along with pH, type of electrolytes, agitation conditions and oil dosages. Both coals (200 mesh) demonstrated approximately 50% reduction in ash content at pH 7, which is an improvement over previously known reports on Indian coals. Chemical structural resemblance between primary components of turpentine oil and predominant π-delocalized aromatic structure of high rank coals could be the reason behind improved adsorption of oil. Our work thus demonstrated the utilization of a natural oil which can be dried easily, readily available and cheap in a significantly demanding commercial process like coal beneficiation. This is expected to deliver a substantial performance and cost improvement over incumbent known bridging liquids.

Strategy of selecting solvent systems for spherical agglomeration by the Lifshitz-van der Waals acid-base approach

A strategy for rationally selecting solvent systems of spherical agglomeration is proposed for the first time. It emphasizes that followed by crystallization and phase separation, spherical agglomeration can be achieved only when the solvent system can induce wetting and adhesion which are estimated by the Lifshitz-van der Waals acid-base approach. Especially for wettability of bridging liquid, solvent and anti-solvent, the strategy indicates that it is of great importance for a successful solvent system. Valid systems therefore are selected in the first place while invalid ones are removed effectively according to the wettability difference. Based on the strategy, valid solvent systems for cefotaxime sodium and benzoic acid spherical agglomeration were selected successfully from 720 and 2184 systems respectively without missing the reported systems. The strategy also predicted no valid systems for potassium chloride, maltitol and trisodium phosphate in the given solvent combinations, which agreed with the experiment results.

Use of Karanja Oil for Recovery of Energy Values from Coal Washery Tailings

The increment in generation of large quantity of fines while mining and beneficiation has led to the serious environmental issues. In this present study, non-edible oil such as Karanja oil was used as bridging liquid to recover coal fines from washery tailings sample, which were discarded while beneficiation process. The coal washery tailings sample was collected from Dhanbad, Jharkhand, with high ash content of 52.74%. The effects of pulp density, oil dosage, and agglomeration time were investigated. From the experimentation, it was found that ash rejection was in the range of 60.90% to 74.96% and organic matter recovery was in the range of 61.14% to 84.77%.

Effect of PEG 4000 in the crystal engineering of Candesartan Cilexetil for solubility enhancement by Polymer Enriched Bridging Liquid technique

Effect of PEG 4000 in the crystal engineering of Candesartan Cilexetil for solubility enhancement by Polymer Enriched Bridging Liquid technique

Study of the effect of pvp k30 in the enhancement of solubility of telmisartan by polymer assisted crystal agglomeration using polymer enriched bridging liquid technique

Polymer Enriched Bridging liquid is a novel approach for enhancing the flow characteristics, properties, solubility and dissolution of poorly water-soluble drugs. is an orally effective II receptor antagonist used extensively for the effective management of hypertension. is a poorly water-soluble drug and an ideal candidate for this approach. PVPK30 is used as the hydrophilic polymer. Various formulations were prepared with the addition of PVPK30 in the bridging liquid by Polymer Enriched Bridging Liquid Technique (PEBL). The preparations were subjected to particle size analysis, characteristics, FTIR, differential scanning (DSC) and Scanning Electron microscopic analysis. The crystal agglomerates were found to be spherical in nature with excellent flow characteristics. The of the pure drug was found to be decreased without any drug-polymer interaction. The saturation solubility studies showed that the optimized formulation STP04 showed 30.695 folds increase in solubility in water and 29.462 folds enhancement in pH 7.5 phosphate buffer. The in drug release studies also confirmed the enhancement in dissolution rate. The stability of the prepared aggregates was determined by accelerated stability studies. The addition of polymer in the bridging liquid during crystallization stage improved the effective incorporation of the hydrophilic polymer in the aggregates. Polymer Enriched Bridging Liquid technique can be considered as an ideal technique for solubility and dissolution enhancement.

Development, characterization and solubility enhancement of poorly water soluble drug telmisartan by polymer enriched bridging liquid technique using peg 4000 as hydrophilic polymer

The solubility and bioavailability enhancement of poorly water soluble drugs has been a foremost challenge in formulation development. Telmisartan belonging to Angiotension II receptor antagonist, extensively used candidate for the treatment of hypertension possess poor water solubility and bioavailability. Polymer Enriched Bridging Liquid (PEBL) method was adopted here for enhancing the flow properties and solubility of Telmisartan. The techniques involve the incorporation of a hydrophilic polymer, PEG4000 into the bridging liquid during the crystallisation process. The drug content determination suggested the better incorporation of polymer into the crystal aggregates. The FTIR analysis showed the absence of any chemical interaction. The DSC analysis showed a significant reduction in the enthalpy and melting point. The crystallinity of Telmisartan was reduced from 50.789 to 34.655% indicated by the reduction in peak intensity analysis and peak area calculation by X-Ray diffraction. The SEM analysis revealed the spherical nature of crystals resulting in the improvement of flow properties. The saturation solubility analysis revealed that the formulation STPG03 has shown 25.86 fold increase in the solubility in water and 24.217 folds in pH7.5 Phosphate buffer. The in vitro dissolution data also supported the results of solubility analysis. Hence PEBL technique provided a better alternative to enhance the flow characteristics, solubility, dissolution and bioavailability of Telmisartan.