Predicting the performance of granulation binders through micro-mechanistic observations

The selection of an appropriate polymeric binder to be used to agglomerate drug with excipients is a critical issue for the development of high shear wet granulation processes for pharmaceutical tablet systems. The aim of the study reported here is to determine the potential for successful granulation through measurement and prediction of the interactions of the polymer solutions with individual drug particles. A novel micro-force balance (MFB) has been used to measure the forces exerted by axially strained liquid bridges of hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) formed between either two paracetamol crystals or between a micro-pipette and a single paracetamol crystal. Video images were obtained simultaneously of the separation sequences for analysis of bridge geometry and contact angles. It was found that the formation of liquid bridges and their ability to bond the particles together depends on the wetting behaviour of the liquid on the particles. Binders that dewet the solid surfaces during separation are shown to produce weaker adhesion forces.     

Behaviour of soft granules under compression: Effect of reactive and non-reactive nature of the binder on granule properties

Granulation is a process where primary powder particles are made to adhere to form multi-particle entities called granules and this is achieved by using a binder. The binders can be broadly classified into two categories viz. reactive (reacts with base powder) and non-reactive (does not react with the base powder). The effect of various parameters related to binder liquid (binder viscosity, addition rate, distribution over the bed etc.) on the mechanism of granulation and physical/mechanical properties of granules is well studied. However, comparison of physical and mechanical properties of granules made via reactive and non-reactive binder using the same base primary particles has not been reported. In this paper, granulation of sodium carbonate primary particles under reactive and non reactive conditions was studied. The mechanical properties of sodium carbonate granules were characterized using single granule compression measurements. The average single granule apparent strength of reactive granules was higher compared to non-reactive granules. It was observed that granules formed using non reactive binder were brittle and showed multiple breakages. However granules made using reactive binder showed single breakage followed by significant plastic flow. In addition, bulk granule compression measurements were also carried out. Known models of Heckel, Kawakita and Ludde, and Adams et al. (developed mainly for pharmaceutical and metal powders) were used to predict mechanical properties of soft detergent granules. The bulk granule compression measurements also showed that reactive granules have higher strength compared to non-reactive granules. However, the absolute values of granule strength obtained from the empirical models were lower than the granule strength obtained from single granule compression measurements.     

The effect of primary particle surface energy on agglomeration rate in fluidised bed wet granulation

The effect of primary particle surface wettability by a binder solution on the rate of agglomeration in a fluid-bed top-spray granulation process was investigated. A model system consisting of hydrophilic and hydrophobic spherical primary particles with a narrow size distribution, and an aqueous solution of hydroxy propyl-cellulose (HPC) as binder, was used. The surface energy of the primary particles was measured by inverse gas chromatography (IGC) and their wettability was characterised by static and dynamic contact angle. Granulation was carried out in a desktop fluid-bed granulator and the resulting granule size distribution and granule microstructure were analysed. The hydrophobic particles gave a wider granule size distribution (larger maximum granule size) than hydrophilic ones under otherwise identical conditions, and the granules were notably rounder and more compact. However, the fraction of un-granulated fines was also higher in the case of hydrophobic primary particles. SEM analysis of granule microstructure revealed that the hydrophilic particles were coated by the binder solution, which left a smaller amount of binder available to form bonds at particle contacts. On the other hand, all of the binder was found to form solid bridges in the case of hydrophobic primary particles. A population balance model was used to explain the observed granulation behaviour.     

The study of granular agglomeration mechanism

The purpose of this study was to determine the effects of the properties of different binders on the granular agglomeration mechanism for the fabrication of pharmaceuticals. The raw materials included calcium carbonate powders with an average particle size of 32-75 μm and four different grades (4000, 6000, 8000 and 10,000) of polyethylene glycol (PEG) used as binders. The raw material was mixed with the binder in a high shear mixer. The surface structure of the granules was analyzed by low vacuum scanning electron microscope (LV-SEM) examination. Three major agglomeration mechanisms are discussed in this study: nucleation, consolidation and coalescence. The results showed that the agglomeration growth rate increased with increasing binder viscosity during the nucleation stage, but the exact opposite phenomenon occurred in the consolidation stage. Observation of the granular surfaces showed the surfaces to be full of fine powder in the nucleation stage, but PEG crystals appeared on the surface in the consolidation stage. During the coalescence stage, the granules grew quickly due to collisions and the surface structures of the granules became full of binders, as can be seen from the LV-SEM photographs.     

LAS acid reactive binder: Wettability and adhesion behaviour in detergent granulation

Linear alkylbenzene sulphonic acid (LAS acid or HLAS) is a reactive binder used in industrial detergent granulation processes. The neutralisation of HLAS with sodium carbonate particles (commercial soda ash) during granulation generates sodium linear alkylbenzene sulphonate (LAS-Na), one of the world's most used anionic surfactants for washing powder formulations. The reaction neutralises the HLAS to increasing degrees, depending on the amount of acid reacted to form the salt. Hence, during granulation the binder has the dual function of forming physical links between the particles and participating in the neutralisation reaction to form the LAS-Na along with some water. The experimental investigation reported here is aimed at establishing whether the extent of HLAS neutralisation and the binder water content influences the wettability and adhesive strength of individual liquid bridges holding particles together in the early stages of granulation.Since LAS acid is a reactive binder, the characterisation of the wetting and adhesive behaviour is complicated by their strong dependency on the kinetics of the binder-powder reaction. Hence, a novel approach to reactive binder studies is presented here, with the experiments carried out using inert particles and acid that had been partially pre-neutralised with Na₂CO₃.Wettability and adhesive force studies have been carried out using a micromanipulator system developed at University College London. Contact angle and spreading velocity measurements show that the higher the degree of neutralisation the lower is the tendency of the liquid to wet the particles. Moreover, it will be shown that particle wetting is strongly dependent on binder water content and relative humidity (RH). A “sticky regime map” is presented as a function of neutralisation and water content to distinguish between wetting and non-wetting conditions. This highlights the importance of controlling the environmental conditions, both during the granulation process and the storage of the product materials.     

Effect of internal binder on microstructure in compacts made from granules

This paper focuses on the influence of granule characteristics on the microstructure of the compact. Alumina granules were prepared with a poly-acryl acid (PAA) or a poly-vinyl alcohol (PVA) as binders by a spray-drying method. Observation with a liquid immersion method shows a significant difference in the binder distribution. Very uniform and non-uniform distributions were noted for the PAA and PVA binders, respectively. PVA binder segregated at surface and subsurface of the granules. The compression strength and deformation behavior were examined on a single granule with a micro-compression testing machine. The granule with the PAA binder has a low yield stress. In the forming process, the relative density of the compact body started to increase at low pressure. Homogeneous internal structures were noted in the green compact at all pressures examined. The granule with PVA binder showed higher yield stress. The internal structure of the compact was inhomogeneous, and large interstices were often observed between granules in the green compact also.     

黏结剂对FCC催化剂孔结构的影响

黏结剂的性能直接影响FCC催化剂的孔结构。运用电镜等分析方法分析黏结剂的粒子特征,根据黏结剂的粒度分布计算黏结剂粒子堆积孔的孔分布,研究黏结剂对FCC催化剂孔结构的影响。结果表明,FCC催化剂的中孔主要来自黏结剂粒子间松散堆积形成的堆积孔。     

The effect of powder size on induction behaviour and binder distribution during high shear melt agglomeration of calcium carbonate

Growth mechanisms in high shear mixer granulation were observed over a wide range of particle size and liquid-to-solid (L/S) ratio. The materials used were calcium carbonate (CaCO₃; size fractions in the range 1.5 to 85 μm) with a binder of polyethylene glycol 6000 (PEG 6k). The binder, solid at room temperature, was added by the “melt-in” method. A 10 L vertical-axis granulator was used, with a chopper and a four-bladed impeller.

The mean granule size and granule size distribution were measured at regular intervals during the agglomeration process by careful sampling and sieving. The uniformity of binder distribution among the granules was also measured.

The growth behaviours of each grade of primary particles were classified and compared. An induction type mechanism was observed with an initial period of slow growth in mean particle size that lasted 2 to 3 min (the induction period). This was followed by a short rapid growth phase lasting 1 to 2 min. The final stage was a plateau of more or less zero growth. Interestingly, the end of the induction period and the onset of rapid growth corresponded to a change in the granule size distribution from bimodal to monomodal and a similar change in the distribution of binder. Induction period growth rate tended to be lower for granules of finer particles, but these grew more rapidly during the rapid growth stage and produced larger granules than the coarser primary particles.

The liquid-to-solid (L/S) ratio had a significant effect on the growth rate during the rapid growth stage but a minor effect on the granule size distribution and binder distribution. Primary particle size had a significant effect on the final average size of granules, the growth rate during the rapid growth stage and the distribution of granule size and binder.     

Foam granulation: Binder dispersion and nucleation in mixer-granulators

Traditional wet granulation method involves spraying of liquid binder onto a moving powder bed to granulate the powder particles in the granulator. A new alternative method of wet granulation has been developed where foam delivery of binder is used to granulate the powder particles.This study investigated binder distribution in wet granulation and focused on the nucleation stage, where nuclei are formed during the initial binder distribution. Nucleation experiments were used to study the formation of nuclei by the foam and spray delivery methods in a high shear mixer-granulator. The distribution of foams on a dynamic powder bed were also investigated by filming small portion of foams as they penetrated into moving powder beds under different powder flow conditions in a high shear mixer-granulator.Nucleation experiments in this study show that foam delivery tends to create a narrower nuclei size distribution during the early stage of wet granulation process compared to spray delivery at the same processing conditions, demonstrating the potential of foam granulation in achieving improved binder distribution. For foam delivery, the nuclei formation is influenced by the foam properties and powder flow conditions in the granulator. The experiments show that the narrowest nuclei size distribution is obtained by granulating with high-quality foam and intensive powder mixing conditions. Coarser nuclei are formed when low-quality foam is dispersed in a less intensively agitated powder. The interactions of foam quality and the powder flow pattern are discussed and two distinct wetting and nucleation mechanisms are proposed: (1) under bumping flow, a low-quality foam tends to induce localised wetting and nucleation. The wetting and nucleation is “foam drainage” controlled. (2) Under roping flow, foam will be dispersed by the motion of the agitated powder. The wetting and nucleation is “mechanical dispersion” controlled.     

Selection of operational parameters for the production of instant soy protein isolate by pulsed fluid bed agglomeration

The objective of this study was to select the optimal operational conditions for the production of instant soy protein isolate (SPI) by pulsed fluid bed agglomeration. The spray-dried SPI was characterized as being a cohesive powder, presenting cracks and channeling formation during its fluidization (Geldart type A). The process was carried out in a pulsed fluid bed, and aqueous maltodextrin solution was used as liquid binder. Air pulsation, at a frequency of 600 rpm, was used to fluidize the cohesive SPI particles and to allow agglomeration to occur. Seventeen tests were performed according to a central composite design. Independent variables were (i) feed flow rate (0.5-3.5 g/min), (ii) atomizing air pressure (0.5-1.5 bar) and (iii) binder concentration (10-50%). Mean particle diameter, process yield and product moisture were analyzed as responses. Surface response analysis led to the selection of optimal operational parameters, following which larger granules with low moisture content and high process yield were produced. Product transformations were also evaluated by the analysis of size distribution, flowability, cohesiveness and wettability. When compared to raw material, agglomerated particles were more porous and had a more irregular shape, presenting a wetting time decrease, free-flow improvement and cohesiveness reduction.     

Mechanical Properties of Dry-Pressed Ceramic Green Products: The Effect of the Binder

The strength of alumina green samples prepared by uniaxial pressing of powders spray-dried with two binders such as poly(ethylene glycol) or poly(vinyl alcohol) is discussed in terms of (i) the adhesive properties of the polymer-rich external layer of spray-dried granules and (ii) the mechanical properties of this layer. A transition from intra- to intergranular fracture is observed when the glass transition temperature of the binder increases. The influence of the binder on the defect size distribution in the green products is investigated using the classical Weibull statistics.     

Composites from WC powders sputter-deposited with iron rich binders

Composite powders of tungsten carbide (WC) and iron rich binder were prepared by an innovative approach, which consists in sputtering of a metallic binder on the tungsten carbide particles. The phase composition, microstructure and mechanical behaviour of WC coated powder composites with binder contents from 6 to 9 wt.% were characterized. η-Phase is early formed during sintering and its effect on the mechanical behaviour was investigated and related to the microstructure and atomic structure. The results show that the presence of η-phase has not a hazardous role in toughness as is previewed in conventional cemented carbide. Despite the presence of η-phase, a good compromise between toughness and hardness was attained in composites prepared from iron rich binders sputtered on WC powders.     

60%肟菌酯·己唑醇水分散粒剂的研制

本研究通过对填料、分散剂、润湿剂、渗透剂、黏结剂等主要助剂的系统筛选,最后确定60%肟菌酯.己唑醇水分散粒剂配方筛选组成,优选配方为肟菌酯含量为20%,己唑醇40%,Morwet IP 3%,分散剂NNO 4%,丁基萘磺酸钠3%,聚乙烯醇0.8%,其余用玉米淀粉补足。根据上述配方加工成60%肟菌酯.己唑醇水分散粒剂,悬浮率在80%以上,质量稳定,分解率低,对水稻纹枯病具有良好的防治效果。     

Composition limits in granulation with active component in the binder

The process of reactive granulation is considered. Sodium carbonate primary particles react with dodecyl‐benzenesulfonic acid droplets to form granules where the active component is an anionic surfactant formed by the reaction. The effect of primary particle size on the maximum binder/solids ratio was systematically investigated and found to be directly proportional to the specific surface area of the primary particles regardless of how this surface area was achieved—whether by monodisperse powders or bimodal powder mixtures. The effect of binder viscosity on the maximum binder capacity has shown a nontrivial behavior: while the maximum binder content increased with increasing binder viscosity for fine primary particles, the opposite trend was observed in the case of coarse primary particles. This behavior was explained by detailed studies of primary particle wetting and binder penetration into particle beds, as well as by microtomography analysis of the internal granule structure. © 2014 American Institute of Chemical Engineers AIChE J, 61: 395–406, 2015     

Investigation of the reason for the softening behaviour of solid propellants

Composite solid propellants consist of an elastomeric polymer binder in which various types of solid particles (oxidizer, fuel, combustion and stabilizing additives, etc.) are incorported. One of the most common state of the art binders is hydroxy-terminated polybutadiene (HTPB). The mechanical properties and the damage behaviour of the solid propellant have important relevance for its application in a rocket motor. Therefore, in this work the softening of crosslinked filled polybutadienes as an effect of mechnical load, and the subsequent recovery were examined at small strains. The contributing factors to the softening are discussed in terms of macroscopic obervable phenomena and of microscopic and molecualr mechnisms which cause those phenomena. It is shown that most of the softening is recoverable because it is due to stress-relaxation at the test conditions used.     

固体推进剂用粘合剂研究进展

介绍了固体推进剂用粘合剂的研究进展,着重介绍了丁羟类、叠氮类、HTPE、NEPE以及硝基和硝酸酯类粘合剂的合成、工艺以及性能研究情况,并对未来固体推进剂用粘合剂的发展进行了展望。     

Effect of inorganic materials on the solidification of heavy metal sludge

Portland cement, cement-fly ash and lime-fly ash binders were used to solidify a synthetic heavy metal sludge containing nitrates of Cr, Ni, Cd and Hg. The sludge to binder (cement, cement-fly ash and lime-fly ash) ratio was kept at 3.33, 1.43 and 1.25, respectively. In addition inorganic substances like Cu, Zn, Pb, Sodium hydroxide and sodium sulfate were added. The molded samples were cured at room temperature for 28 days. The solidified samples with and without interference were examined for the change in their bulk density and compressive strength at definite time intervals during curing. All the metals and sodium salts added increased the average bulk density of the final product with increase in concentration (2% to 8%) with all the binder systems. The samples containing copper and lead decreased the compressive strength at all the concentrations added with CFA and LFA binders. Zn had the largest effect on all the three binder systems, lowering the strength of all samples at all the days and concentrations except the 2% Zn with CEM binder. However, Pb had only minor effect on the compressive strength with CEM binder and values remained almost constant at all the times and concentrations studied. In contrast, the effect of sodium sulfate was less marked while sodium hydroxide increased the rate of set and 28-day compressive strength of samples containing cement as binder. These observations confirm the need for specific studies of the waste and binder prior to the selection of a solidification process for the treatment of hazardous wastes. The results provide a better understanding of materials that may interfere with the immobilization of waste constituents and provide information on the possible mechanism of the interfering effects.     

Multi-component granulation in a fast fluidized bed

The granulation of multi-component particles was conducted in a fast fluidized bed with an atomizing binder solution. The effects of gas velocity and binder droplet diameter on granulation rate, granule size distribution and granule composition were studied. The granulation rate and granule yield were determined by the balance between the agglomeration rate of feed particles and the disintegration rate of granules because there was no secondary granulation. With the increase in gas velocity and the reduction in binder droplet size, the agglomeration rate of feed particles decreased but the disintegration rate of granules increased, resulting in a reduced granule yield. Despite the larger fraction of small particles in the granules, the homogenous granulation of multi-component particles was achieved.     

Granule performance of zirconia/alumina composite powders spray-dried using polyvinyl pyrrolidone binder

Polyvinyl pyrrolidone (PVP) was used as a binder in spray-drying a slurry containing zirconia/alumina composite powder and its influence on granulation and granule deformability was compared with those of polyvinyl alcohol (PVA) and polyethylene glycol–hydroxyethyl cellulose cobinder (PEG–HEC). Although the most spherical solid granules were obtained from the slurry containing PEG–HEC, the granules containing PVP were the most deformable during compaction. It was apparent that a high-viscosity organic additive mixture added to the slurry resulted in highly spherical solid granules, and a low T_g of the mixture led to a high deformability. The flexural strengths of composites prepared from granules containing PVP, PEG–HEC, and PVA were 634, 578, and 468 MPa, respectively, which corresponds to the ascending order of T_g of the binders mixed with plasticizers.     

Computer simulation of granule microstructure formation

The diagenesis (porous microstructure evolution) of granules formed by a layering growth mechanism in a wet granulation process has been modelled. The model includes the packing of primary particles with a given size and shape distribution, and the deposition, spreading, and solidification of binder droplets within the growing granule. The dependence of granule porosity on the binder/solids ratio, primary particle size and morphology, and the rates of binder spreading and solidification has been investigated. The results are presented in the form of structure maps relating volume-averaged microstructure parameters with dimensionless groups including the ratio of droplet spreading and solidification times and the mean time between particle collisions. These graphs can guide the selection of process operating conditions or formulation ingredient properties required to obtain a particular granule microstructure.