Screening pharmaceutical excipient powders for use in commercial 3D binder jetting printers

Binder jetting is an additive manufacturing technique that creates three-dimensional constructs from a powder feedstock. It is used by several industries, including pharmaceuticals. This additive approach to manufacture provides several functional benefits that are not easily achievable using conventional manufacturing methods. There is currently only limited publicly available knowledge that details the requirements of an effective binder jetting powder. Specifically in the pharmaceutical industry, since the 2015 release of Spritam®, a binder-jetted tablet containing levetiracetam, no new pharmaceutical tablets have been produced using such methods.There appears to be gap in powder technology expertise and the development of 3D printing processes. Our goal is to enhance our knowledge in terms of powder flow, powder wetting and powder binding to link particles with process and build the capability to create a greater range of powders suitable to be binder-jetted into new products. After initially screening several standard pharmaceutical excipient powders for their relevant properties, two candidates showed best fit potential for use in binder jetting, specifically microcrystalline cellulose (Pharmacel 101 and 102) and lactose (Lactohale 200). Using simple formulations of these pharmaceutical excipient powders as a model, we analysed for printability and powder performance using a range of quantitative parameters including dimensional accuracy, construct hardness, friability, porosity and surface finish. In general, formulations of these powders showed good printability, but some powder blends produced constructs with more obvious manufacturing imperfections. Several routes to improve the printability of these pharmaceutical powders are proposed for future works. Ultimately, this work provides a fundamental basis to start to quantitatively assess the potential of standard pharmaceutical excipient powders in binder jetting printers using powder characterisation techniques and print quality outcomes.     

Elastic modulus of 316 stainless steel lattice structure fabricated via binder jetting process

This study mainly evaluates the elastic modulus of 316 stainless steel lattice structures fabricated via binder jetting process. In this present research, both solid and lattice samples are designed and fabricated by binder jetting process for two different types of mechanical tests. Besides experimental study, a numerical model based on energy approach has been proposed to predict the effective elastic modulus of fabricated lattice samples. By comparing the calculated results of the proposed numerical model with the experimental results, the established model is proved to be validated. This numerical model can be used to determine the parameters of lattice structures fabricated by binder jetting process for desired mechanical properties. At the end, both advantages and disadvantages of the lattice structures fabricated by binder jetting process are analysed. Based on this analysis, the potential application and future research work are pointed out.     

3D printing of tuneable agglomerates: Strain distribution and effect of internal flaws

The current study presents a novel and reliable method for producing 3D printed agglomerates with different colour distributions and material properties with 2-fold aims: providing feasible and accurate control on compression of agglomerates under different compression angles, and better tracking of individual particle position after agglomerate breakage. Multi-coloured agglomerates in cubic tetrahedral and random sphere shapes were printed with both rigid and soft bonds. The printed agglomerates were analysed thoroughly of their surface and structural properties including surface roughness and printing accuracy. The agglomerate breakage behaviours under static compression were analysed as a function of bond strength, loading rate and loading directions, with strain distribution plotted over the random sphere agglomerate structure. In addition, agglomerate structures with designed internal macro-voids in different positions and sizes were also created for breakage study, in an effort to better understand parameters governing the mechanical properties of agglomerates with cavities and voids which is inevitable in particle industry but poorly understood at present.     

氧化锆粉料中颗粒聚集状态的研究

用各种测试方法研究了氧化锆颗粒的聚集状态,如用 BET 方法测定了粉料的比表面积,用扫描电镜和以计算机控制电子束的扫描电镜测定了颗粒的平均粒径及粒度分布等。同时,在水介质中测定了颗粒的ξ—电位和相应的 pH 值。实验结果表明:颗粒的聚集状态与其表面的荷电状态有关。粉料在球磨过程中,表面的荷电状态发生变化,因此颗粒的聚集状态也将随之改变。根据实验结果,提出了用以表示氧化锆颗粒间“软”聚集状态强度的参数。     

Rapid pattern based powder sintering technique and related shrinkage control

Rapid Pattern Based Powder Sintering (RPBPS) is a new rapid tooling technique proposed by the authors. It is an integration of three techniques: rapid prototyping; lost wax casting; and powder sintering. The main advantages of the RPBPS technique compared with other tooling techniques are low investment and production cost, short production cycle and a variety of materials of products. One of the key technical problems is how to calculate and control the shrinkage during three processes in the RPBPS to improve the accuracy of products. The total linear shrinkage of the products made with the RPBPS can be controlled within 3.5% by using the selected binder type and binder ratio, suitable compacting pressure and specially designed ramp temperature program in the sintering and infiltration processes.     

Dilute phase pneumatic conveying of whey protein isolate powders: Particle breakage and its effects on bulk properties

Breakage of dairy powder during pneumatic conveying negatively affects the end-customer properties (scoop uniformity and reconstitution). A dilute phase pneumatic conveying system was built to conduct studies into this problem using whey protein isolate powder (WPI) as the test material. Effects of conveying air velocity (V), solid loading rate (S_L), pipe bend radius (D), and initial particle size (d) on the level of attrition were experimentally studied. Four quality characteristics were measured before and after conveying: particle size distribution, tapped bulk density, flowability, and wettability. The damaged WPI agglomerates after conveying give rise to many porous holes exposed to the interstitial air. V is the most important input variable and breakage levels rise rapidly at higher airspeeds. The mean volume diameter D[4,3] decreased by around 20% using the largest airspeed of 30 m/s. Powder breakage is also very sensitive to particle size. There appears to be a threshold size below which breakage is almost negligible. By contrast, S_L and D show lesser influence on powder breakage. Reflecting the changes in particle size due to breakage, tapped bulk density increases whereas wettability decreases as a result of an increase in conveying air velocity. However, breakage does not show a significant effect on powder flowability as powder damage not only decreases particle size but also changes the particle’s surface morphology.     

Development of Novel Binder for Hardmetal Powder Extrusion Molding

A novel binder system for hardmetal powder extrusion moulding(PEM) process has been developed.The binder system comprises a major fraction of a mixture of low molecular weight components (LMWCs) and a minor fraction of very finely dispersed polymer.The feedstocks are mixed as a thick slurry at a suitable temperature and are rapidly homogenized by stirring at an adequate shear force.The binders are removed by thermal debinding.The thermal debinding mechanism has been investigated by thermogravimetry(TG) and differential thermogravimetry(DTG).At the first stage of debinding,the LMWCs are removed.These open up pore channels which allows much faster removal of the remaining polymer component during the subsequent stage.Ihe microtructures of the moulded green parts were observed by scanning microscopy(SEM).The debound samples were sintered at different temperatures,and the sintered samples properties were measured.     

利用引射结构提高离心泵的汽蚀

 提出在普通转速离心泵的入口处或高速离心泵的前置诱导轮前增加引射装置来提高泵的汽蚀性能，给出单孔喷嘴轴向直引射和环形多喷嘴轴向斜引射两种引射装置的结构示意图．探讨了引射装置设计的理论基础及优化设计的目标，指出采用引射装置是提高泵汽蚀性能的新方法．     

Performance evaluation of ProJet multi-material jetting 3D printer

The purpose of this paper is to quantitatively evaluate the performance of a multi-material jetting 3D printer, ProJet 5500X, especially the capability for micro manufacturing. Unlike other single material 3D printer, ProJet 5500X uses photopolymers as the build material and wax as the support material. The building performance was evaluated by building a modified version of the standard benchmark model with a high-resolution printing mode. The dimensional error, forming quality and surface roughness of the printed parts have been measured and analysed using a microscope, a 3D coordinate measuring machine and a surface profilometer. Using wax as the support material, fine features as small as 0.25?mm, lateral features and sharper edges could all be properly built, despite the rough side surfaces observed in the printed part. Identical features (3?mm pins) were precisely built with an accuracy of 15?µm. The research provides first-hand detailed performance knowledge in the ProJet system for understanding the working principle and comparison with other 3D printing systems.     

金属粘结剂喷射增材制造技术发展与展望

目的 介绍了粘结剂喷射增材制造(BJAM)技术打印金属零件的发展历程、技术特点、打印材料和应用领域,重点分析了影响金属BJAM零件质量的主要因素,讨论了金属BJAM技术的研究重点.方法 归纳了金属BJAM技术的重要发展节点及现阶段技术的成熟度;总结了原材料、打印及烧结工艺参数对BJAM打印金属零件质量的影响规律;按材料种类讨论了BJAM打印金属零件的致密度、微观组织及力学性能.结论 通过分析金属BJAM技术可实现高效率、低成本制造金属零件,但仍存在烧结致密度低和收缩严重等问题,指出了改善铺粉质量、开发新型粘结剂和模拟预测烧结收缩等是金属BJAM技术未来发展的重点方向.     

Evaluation of Critical Binder Properties Affecting the Compactibility of Binary Mixtures

The aim of this study was to identify essential physical and mechanical properties of various binders and to investigate their influence on the tensile strength and porosity of tablets made from binary mixtures with sodium bicarbonate. The binders were characterized according to axial and radial tensile strength after compression into tablets, yield pressure and minimum porosity during compression, and elastic recovery after compression. The addition of a binder generally resulted in an increase in the tensile strength and a decrease in the porosity of the sodium bicarbonate tablets. The location of the binder in the voids between the sodium bicarbonate particles thus decreasing the porosity of the tablet seemed to be an important consideration. Consequently, the addition of binders with a low yield pressure value and a relatively small elastic recovery value (e.g., polyethylene glycol 3000 and polyvinylpyrrolidone) resulted in tablets of low porosity and high tensile strength, especially in the axial direction. The tensile strength of the pure binder also seemed to be important, especially for binders with a lower degree of deformability (e.g., microcrystalline cellulose and pregelatinised starch). The results also indicated the value of using both axial and radial tensile strength measurements in assessing the effect of a dry binder and showed that the importance of different binder properties varied according to the direction of the tablet strength measurements. The results demonstrated that the applied characteristics of the binders used in this study may serve as a useful tool in evaluating the effectiveness of binders.     

基于数值仿真的气动喷射阀回流间隙的优化

气动喷射阀是微电子封装中不可或缺的封装设备,但现有气动喷射阀在喷射高黏胶液时仍不能完全满足工业界对胶滴一致性的需求,原因在于其喷射高黏胶液时常出现因喷射速度太小而导致的挂胶漏喷现象.要减小上述现象的发生概率,就必须提高现有气动喷射阀的高黏流体喷射能力.回流间隙作为气动喷射阀的关键尺寸,直接影响着喷射阀的喷射能力.为了通过优化回流间隙来提高喷射能力,首先建立气动喷射阀的胶液喷射数值仿真模型并通过实验验证其可靠性,同时基于不同回流间隙的仿真数据建立了相应的高斯拟合模型.然后利用拟合模型以胶滴滴落速度为优化目标对回流间隙进行优化,通过优化前后的喷射对比验证了优化结果的可靠性,最后获得气动喷射阀的最优回流间隙.     

A review of current techniques for the evaluation of powder mixing

Blending a mixture of powders to a homogeneous system is a crucial step in many manufacturing processes. To achieve a high quality of the end product, powder mixtures should be made with high content uniformity. For instance, producing uniform tablets depends on the homogeneous dispersion of active pharmaceutical ingredient (API), often in low level quantities, into excipients. To control the uniformity of a powder mixture, the first required step is to estimate the powder content information during blending. There are several powder homogeneity evaluation techniques which differ in accuracy, fundamental basis, cost and operating conditions. In this article, emerging techniques for the analysis of powder content and powder blend uniformity, are explained and compared. The advantages and drawbacks of all the techniques are reviewed to help the readers to select the appropriate equipment for the powder mixing evaluation. In addition, the paper highlights the recent innovative on-line measurement techniques used for the non-invasive evaluation of the mixing performance.     

基于等质量变壁厚球缺罩聚能杆式射流成型特性研究*

基于变壁厚球缺罩质量恒定假设,通过改变药型罩内表面曲率半径rx 和罩顶厚度s,调整药型罩的结构,建立了δs与rx 设计参数计算模型;采用LS-DYNA3D显式非线性动力有限元程序,对不同结构变壁厚球缺罩形成聚能杆式射流的过程进行三维数值模拟;设计出罩顶厚度改变量δs 在（-1．2～＋1．2） mm范围内的7种不同结构变壁厚球缺罩方案,研究其形成聚能杆式射流的形态和各项性能参数的变化规律,并与等壁厚药型罩形成的聚能杆式射流参数进行对比分析。研究结果表明：变壁厚球缺罩对杆式射流的形状、长度、密实度和断裂时间等性能参数均有较显著影响;当δs ＝-0．4mm时,杆式射流头部速度为3317m/s,并且速度梯度分布合理,杆式射流的综合性能较优。     

Preparation and Properties of Slag Wool Board using Modified Polyvinyl Alcohol as Binder

Slag wool boards were produced by using slag wool as the main raw material and adding modified polyvinyl alcohol (PVA) as the binder. The microstructure, thermal conductivity, compression strength, hydrophobicity, and other properties of the slag wool board were analyzed by using scanning electron microscopy, thermal conductivity tester, electronic universal testing machine, and other equipments. Also, the influence of different types and amount of binder on the properties of the slag wool board was studied. The results show that the addition of silica sol can improve the high temperature resistance of the slag wool board, and the addition of borax can improve the hydrophobic rate and compression strength of the slag wool board. Also, the concentration of PVA has obvious influence on the usage of silica sol and borax. In this study, we found that the optimal ratio of the binder should be 3 wt% addition of PVA, 20 wt% addition of silica sol, and 0.2 wt% of borax (relative to the amount of PVA), under the condition of satisfying the performance index of slag wool board and the convenience to spray the adhesive.     

Effect of Binder Composition on the Shrinkage of Chemically Bonded Sand Cores

Modern foundries increasingly use chemically bonded no-bake sand cores and molds because they provide ease of molding, good surface finish, and collapsibility. One of the most popular binder systems is alkyd oil urethane no-bake system comprising three parts: alkyd resin, catalyst, and crosslinking agent. Their amounts and ratios can influence mold shrinkage, and thereby dimensional quality of the resulting casting. With rising emphasis on net-shape casting, there is a need to optimize the binder composition to minimize dimensional errors, while achieving the desired bench life, stripping time and hardness. This work investigates the effect of binder composition on the dimensions of chemically bonded sand cores with respect to time. The maximum shrinkage of 0.15% over length was observed when resin content was 2.4% by weight of sand. The rate of shrinkage increased with the amount of catalyst. Measurement of core hardness and reduction in weight, followed by SEM studies, provided a better understanding of the underlying phenomena, especially formation of resin bridges between compacted sand particles and evaporation of solvent. This work is expected to aid in selection of the most appropriate binder composition for a given set of molding process constraints and cast product requirements.     

Investigating the effects of excipients on the powder flow characteristics of theophylline anhydrous powder formulations

Pharmaceutical excipients may have a great effect on properties affecting tablet production. To determine if formulations containing theophylline anhydrous would have properties allowing them to be easily tableted, functional parameters affecting powder flow were evaluated. The Carr Flowability Indices were used for this evaluation. Formulations to be studied include theophylline anhydrous as the active ingredient, hydrous lactose and dicalcium phosphate dihydrate as diluents, polyvinylpyrrolidone as a binder, and fumed silica as a flow promoter. The effect of each component on powder flow is discussed.     

Metallography of powder metallurgy materials

The primary distinction between the microstructure of an ingot metallurgy/wrought material and one fabricated by the powder metallurgy route of pressing followed by sintering is the presence of porosity in the latter. In its various morphologies, porosity affects the mechanical, physical, chemical, electrical and thermal properties of the material. Thus, it is important to be able to characterize quantitatively the microstructure of powder metallurgy parts and components. Metallographic procedures necessary for the reliable characterization of microstructures in powder metallurgy materials are reviewed, with emphasis on the intrinsic challenges presented by the presence of porosity. To illustrate the utility of these techniques, five case studies are presented involving powder metallurgy materials. These case studies demonstrate problem solving via metallography in diverse situations: failure of a tungsten carbide-coated precipitation hardening stainless steel, failure of a steel pump gear, quantification of the degree of sinter (DOS), simulation of performance of a porous filter using automated image analysis, and analysis of failure in a sinter brazed part assembly.     

Preparation of Ceramic Composite Pipes Through Paste Extrusion

An experimental investigation was carried out in order to prepare ceramic composite pipes used for tubular solid oxide fuel cells by using a multi-billet extrusion technique. Particular emphasis was given to the forming possibility and extrusion behavior of a two-layer pipe consisting of NiO-YSZ(PSZ) (anode) and YSZ (electrolyte). It is shown that the extrusion pressure and binder content required decrease with increasing the fraction of nickel oxide in the anode layers. The porosity in the anode layers depends on the binder content in pastes. It is feasible to prepare anode/electrolyte composite pipes by means of co-extrusion of different pastes.Furthermore, it is possible to obtain sound sintered pipes even under pressureless sintering conditions.