Effects of granule density on strength and granule related defects in zirconia

A suspension of zirconia powder (TZ3YSE) with a solids loading of 50 vol% was prepared by ball milling. Binders were added and some of the suspension was diluted to 40, 30 and 20 vol% before freeze granulation was performed. A spray dried material (TZ3YSEB) was used as a reference. The pore size distribution of the different granules was evaluated and from the microstructure it was shown that inhomogeneities were present in both the freeze granulated as well as in the spray dried granules. In addition, the density, microstructure as well as the strength of sintered materials prepared from the granules were studied. The results showed that a high green density or sintered density was not sufficient in order to achieve a high strength material. It was further shown that the strength was significantly influenced by the granule density and not by the inhomogeneities found in the granules.     

流化床侧喷技术制备乳糖颗粒的工艺

采用流化床侧喷制粒技术,以羟丙基甲基纤维素K4M为粘合剂制备乳糖颗粒. 以颗粒粒径分布与流动性为主要评价指标,得到优化的制备参数为：粘合剂浓度1.5%,用量2.0%,喷液速度14~18 g/min,雾化压力1.5′105 Pa. 200~355 mm的目标粒子收率在85%以上,颗粒休止角均小于34o,压缩度均小于10%,流动性好,光学显微镜下颗粒呈类球形. 制备工艺稳定,重现性好.     

Production of granola breakfast cereal by fluidised bed granulation

In the fluidised bed granulation process the effect of nozzle air pressure and binder spray rate on key aggregate quality attributes were studied. The experimental results show that a decrease in nozzle air pressure leads to larger mean granule size. The combination of lowest nozzle air pressure and lowest binder spray rate results in granules with the highest levels of hardness and crispness. The combination of low nozzle air pressure and low binder spray rate results in the least distribution span. Granola hardness was affected by nozzle air pressure. Nozzle air pressure and binder spray rate did not have significant effect on crispness.     

Particle design for dry powder inhalation via binderless powder coating by pressure swing granulation

Novel formulation for dry powder inhalation (DPI) particularly appropriate for very dilute drug concentration was developed based on the pressure swing granulation (PSG) technology. PSG was applied to the granulation of excipient lactose particles and to the coating/dusting of lactose granules with fine model drug particles. Size distribution and granule strength as well as the dispersibility of the drug particles for DPI were found to be successful for practical use. The drug particles dispersed into the respirable aerodynamic size range of 1-7 μm from the E-haler® was 53.9% for 1% coating/dusting (i.e. 1% drug in product granules) and 46.3% for 2%. E-haler® was capable of emitting 89.8% and 83.2% of drug particles charged for cases for 1% and 2% coatings, respectively.     

Supercritical CO2 Spray Drying of Ethyl Cellulose (EC) for Preparing Microparticles

Even though common spray drying has been widely used for drying food and related products, the effect of drying conditions of supercritical CO₂ spray drying on the particle sizes of dried products has not been well studied. The objective of this study was to study the effect of drying conditions and design parameters on the particle sizes of biomaterials dried with supercritical CO₂ spray drying. The ethyl cellulose (EC) microparticles were prepared with supercritical CO₂ as the dry medium using an experimental spray-drying apparatus. This research studied the influences of spray nozzle diameter, mass ratio of gas to liquid, solution concentration, temperature, and pressure on the physical characteristics of ethyl cellulose microparticles. The results indicated that the average size of the dried particles ranged from 1.07 to 9.84 µm. The spray nozzle with 8-mm diameter produced smaller microparticles with narrower distribution than the 4-mm spray nozzle. The average particle size increased with the increase of the ratio of gas to liquid. Also, the average size and distribution of the microparticles increased with the rise of temperature and solution concentration but decreased with the increase of pressure.     

Hot melt granulation of coarse pharmaceutical powders in a spouted bed

The hot melt granulation of a coarse pharmaceutical powder in a top spray spouted bed is described. The substrate was lactose-polyvinylpyrrolidone particles containing or not acetaminophen as a drug model. Polyethylene glycol (MW, 4000) used as binder was atomized onto the bed by a two-fluid spray nozzle. The granulation experiments followed a 2³ factorial design with triplicates at the center point and were carried out by varying the spray nozzle vertical position, the atomizing air flow rate and the binder feed rate. Granules were evaluated by their pharmacotechnical properties like size distribution, bulk and tapped densities, Carr index, Hausner ratio and tableting characteristics. Analysis of variance showed that granule sizes were affected by the PEG feed rate and atomizing air pressure at the significance levels of 1.0 and 5.0%, respectively, but spray nozzle distance to the substrate bed was not significant. The spray conditions also affected granule flow and consolidation properties, measured by the Carr index and Hausner ratio. Measured densities, Carr indexes and Hausner ratios proved that granules flowability and consolidation properties are adequate for pharmaceutical processing and tableting. Tablets prepared with acetaminophen-containing granules showed good properties and adequate release profiles in in vitro dissolution tests. The results indicate the suitability of spouted beds for the hot melt granulation of pharmaceutical coarse powders.     

Microstructural Effects on the Mechanical Properties of SiC‐15 vol% TiB2 Particulate‐Reinforced Ceramic Composites

The microstructures and mechanical properties were studied for two different SiC ceramics containing 15 vol% of TiB₂ particulates. The first was prepared from commercially available spray‐dried granules and the second by blending individual SiC and TiB₂ powders. The average TiB₂ particle sizes were 2.7 μm for the ceramic prepared from blended powders, which had a uniform distribution of TiB₂, and 2.3 μm for the ceramic prepared from spray‐dried granules, which had a nonuniform distribution of TiB₂ agglomerates. Although the two ceramics had hardness values of 26 GPa, the other properties were different. For example, the fracture toughness was 4.3 MPa·m^1/2 for the ceramic prepared from blended powders compared to 3.1 MPa·m^1/2 for the ceramic prepared from spray‐dried granules. In contrast, the Weibull modulus for the ceramic prepared from spray‐dried granules was 21 compared to 12 for the other. Calculations predicted spontaneous microcracking in the ceramic prepared from spray‐dried granules, which was confirmed by analysis of the microstructure. The presence of microcracks accounted for the higher Weibull modulus, but lower flexural strength, Young's modulus and fracture toughness for the ceramic prepared from spray‐dried granules.     

粉体干燥-造粒-微波加热干燥新工艺

从讨论粉体干燥、粉体造粒、颗粒干燥等技术特性出发，试图科学地建立一条新的粉体前期干燥一造粒一微波加热干燥工艺路线。先进行恒速阶段的物料干燥，使物料除湿，成为湿含量低于20％（湿基）的物料。低湿含量的物料用压力法造粒，此时不仅易于成粒，成粒率高，且颗粒粒度均匀，强度高，将这种颗粒物料用微波加热进行干燥，可以使颗粒内部的湿分迅速排除，从而获得合格湿分要求的产品。     

Comparison of freeze drying and spray drying to obtain porous nanostructured granules from nanosized suspensions

This work studies the spray drying and freeze drying of different nanosized ceramic materials and the physicochemical characteristics of the obtained granules. Colloidal suspensions of alumina, titania, and a 87/13 mixture were studied. The influence of temperature, pressure, nozzle diameter, and solids loading on the morphology and characteristics of dried granules were evaluated. It was demonstrated that these processing parameters have practically no influence, and the only parameter determining the granules characteristics is the solids content of the suspensions, in both processes. Spray drying leads to a monomodal distribution with higher granule size, while freeze drying produces more porous granules, with a bimodal intragranular distribution. The flowability of spray-dried powder is better than that of the freeze-dried powder and suit better the requirements of a feedstock targeted to obtain coatings by plasma thermal spraying whereas freeze drying can produce high porosity, softer granules.     

THE RELATIVE INFLUENCE OF DIELECTRIC AND OTHER DRYING TECHNIQUES ON THE PHYSICO - MECHANICAL PROPERTIES OF A PHARMACEUTICAL TABLET EXCIPIENT. PARTI: COMPACTION CHARACTERISTICS.

The relative Influence of nine techniques for drying wet granulated microcrystal-lline cellulose (MCC) on the subsequent compaction characteristics was studied In terms of the tensile strength and corrected work of failure of the tablets. Wet granulation resulted in a substantial decrease in compatibility. However, the drying technique used was found to affect the degree of loss in compatibility. In general, microwave-vacuum drying using the “high” process type resulted in the production of granules with the highest compatibility followed by freeze drying and fluidized bed drying. Granules dried under ambient conditions, and granules tray dried to “just dry” or “over dried” conditions resulted In tablets possessing approximately comparable compatibilites, with the poorest compaction characteristics being exhibited by vacuum dried granules, in addition It was found that use of a “low” drying process type during microwave- vacuum drying yielded granules with inferior compaction characteristics to those dried by the “high” process type. Radio frequency drying was found to yield granules which produced tablets having slightly inferior tensile strength to tray dried material, although the tablet work of failure values were comparable. The effect of drying technique on the subsequent compaction characteristics was not found to be directly related to the moisture content of the granules.     

流化床喷雾造粒技术进展

本文介绍了流化床喷雾造粒技术,包括造粒机理、操作方式、影响因素等。流化床喷雾造粒是将溶液、悬浮液或熔融液喷雾到已经干燥或不完全干燥颗粒的流化床床层内,在同一设备内一步完成蒸发、结晶、干燥或化学反应的造粒过程。流化床造粒操作对颗粒的尺寸、形状要求不高,所得到的产品无结块、具有良好的流动性能。与其他传统的造粒方法相比,流化床造粒具有工艺流程简单、设备装置紧凑、投资省、生产强度大等优点,越来越引起人们的关注。     

Separation of CNF agglomerates from a ceramic suspension by spray drying technique

Aqueous silicon nitride based composite suspensions with the addition of 3.1 wt% of carbon nano-fibers (CNFs) were dried using two different drying techniques: spray drying and freeze drying. The paper deals with optimisation of parameters of the spray drying processwith the aim of maximising the yield and improve the quality of the granulate. Freeze drying was selected as a reference drying method, because no powder separation can occur in the course of the process. Prepared suspensions were spray dried at 4 different temperatures: 80, 110, 140 and 180 °C. After each run, two types of granules were obtained: from the separation flask and from the product vessel. Thermo-gravimetric analysis together with SEM examination show that spray drying results in separation of CNFs agglomerates. The granules from separation flask are always enriched by CNFs agglomerates whilst the granules from product vessel have reduced content of CNFs agglomerates. Sintering of spray-dried granules from the product vessel resulted in the composite with uniform microstructure, low amount of CNFs agglomerates and high relative density.     

Preparation of dense spherical AlN fillers by aqueous granulation and post-sintering process

Herein, an innovative two-step method was proposed to prepare dense spherical aluminum nitride (AlN) fillers for the application of insulating encapsulants, involving spray granulation from AlN-based suspensions and subsequent sintering process to achieve full density. According to investigations on the dispersing ability of powders, the AlN-based aqueous suspensions with various solid loading were firstly prepared for spray granulation. It was indicated that a low-viscosity and high-concentration suspension could enhance the sphericity and uniformity of green granules and simultaneously facilitate the high green density. The spherical AlN green granules were further sintered with boron nitride (BN) powders, which played a role as the interval material to retain the spherical morphology and hinder the agglomerations of AlN granules. The distinct impacts of BN powders, sintering temperatures and additive species on the overall properties of resultant AlN fillers were further studied and rationally uncovered. Based on these results, spherical AlN granules with superior dispersion, low porosity and an average particle size of more than 40 µm were successfully fabricated via the newly-developed two-step method, showing promising potentiality for the application as thermal-conductive fillers.     

Novel mechanistic description of the water granulation process for hydrophilic polymers

The purpose of this study was to investigate the mechanism behind the water granulation of the hydrophilic polymers HEC and HPMC. To gain insight into this process, properties of the polymers, e.g. molecular weight, viscosity, particle size distribution and interaction with water, were related to torque values measured during the granulation process and to the properties of the dried granules. The torque values in the high shear mixer were determined as function of the binder ratio (g added water per g dry polymer). These methods revealed differences in torque behavior between the polymers, indicating that the viscosity and gelling rate were important parameters determining the torque values. Bimodal particle size distributions for both HEC and HPMC were obtained when performing the granulation in the high shear mixer. A novel granulation mechanism is presented relating the water uptake, the viscosity and the gelling rate to the consolidation and coalescence of the granules. Furthermore, the breakage of the granules is suggested to be limited for hydrophilic granules obtained by water granulation.     

On the small composite granules formed in a continuous rotating conical vessel containing grinding media: effect of the methods of feeding powder on the size and structure of binary composite granules

To investigate the effect of the methods of feeding SiC and CaCO₃ powders on the size and structure of binary composite granules made of the powders, experiments were performed by a simultaneous operation of granulation, grinding and separation in a continuous rotating conical vessel using two kinds of methods for feeding the binary powder. The structure of a composite granule was characterized by comparing the granule size with the size of the SiC-agglomerates contained in the granule.

It was found that (i) by feeding dry SiC with CaCO₃ powders, it was difficult to obtain composite granules smaller than 0.3 mm in size, and that (ii) by feeding SiC-powder with binder in a slurry state, it was possible to make composite granules of larger than at least 0.13 mm, though the structure of composite granules depended on the concentration of SiC-powder in the slurry.     

Mapping of regimes for the key processes in wet granulation: Foam vs. spray

The evaluation of foam and spray granulation mechanisms and their performances in achieving uniform liquid distribution in a high‐shear mixer‐granulator is presented. A regime map is presented to describe the granulation mechanisms for the foam and spray systems. Foam and spray granulation are shown to successfully create granules of well‐distributed moisture at the end of wet massing despite there was a deviation from the theoretical moisture content at the end of binder addition. In the wetting and nucleation regime, spray granulation involves drop penetration nucleation outside of the drop‐controlled regime, whereas foam granulation operates favorably in the mechanical dispersion regime. For foam granulation, mechanical dispersion produces more uniform granule‐size distributions below the overwetting limit. Spray granulation exhibits steady granule growth, whereas foam granulation shows induction granule growth followed by rapid granule growth. The regime map provides a basis to customize formulations and compare the different foam and spray granulation mechanisms. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2328–2338, 2013     

Coupled CFD-PBE Simulation of Nucleation in Fluidized Bed Spray Granulation

Fluidized bed spray granulation is used to produce porous granular particles from suspensions, solutions, and melts. It is the general aim of our work to provide a physics-based simulation tool for this process. For this the process-relevant mechanisms such as droplet deposition, dust integration, and drying are implemented using computational fluid dynamics (CFD) to generate growth kinetics of the granules and of the dust particles. The latter gives rise to the nucleation rate. This kinetics is applied to simulate the development of the particle size distribution of granules for a continuously operated fluidized bed spray granulation process using population balance equations of the granules.     

Controlling the morphology of ceramic and composite powders obtained via spray drying – A review

Spray drying is one of the most convenient methods for drying suspensions (slurries) and for granulation of materials. Spray dried powders have good flowability, narrow size distribution and controllable morphology. Morphology of powder particles (also called granules or microspheres) strongly affects the use and handling of powders. This review discusses the latest research on parameters that affect morphology and size of granules obtained by spray drying: atomization parameters, properties of sprayed slurry, mass transfer etc. The formation of hollow and dense granules is extensively reviewed. Granule size is affected by droplet size, slurry concentration and initial particle size. Morphology mostly depends on size distribution of initial ceramic particles, agglomeration tendency in the slurry and mechanical strength of the shell of a granule during the drying process compared to capillary force of the suspension liquid. Polymer additives (e.g. binders and lubricants) change the properties of granule shell and the evaporation of moisture; thus, polymer additives significantly affect morphology.     

THE RELATIVE INFLUENCE OF DIELECTRIC AND OTHER DRYING TECHNIQUES ON THE PHYSICO - MECHANICAL PROPERTIES OF A PHARMACEUTICAL TABLET EXCIPIENT. PARTI: COMPACTION CHARACTERISTICS.

The relative Influence of nine techniques for drying wet granulated microcrystal-lline cellulose (MCC) on the subsequent compaction characteristics was studied In terms of the tensile strength and corrected work of failure of the tablets. Wet granulation resulted in a substantial decrease in compatibility. However, the drying technique used was found to affect the degree of loss in compatibility. In general, microwave-vacuum drying using the “high” process type resulted in the production of granules with the highest compatibility followed by freeze drying and fluidized bed drying. Granules dried under ambient conditions, and granules tray dried to “just dry” or “over dried” conditions resulted In tablets possessing approximately comparable compatibilites, with the poorest compaction characteristics being exhibited by vacuum dried granules, in addition It was found that use of a “low” drying process type during microwave- vacuum drying yielded granules with inferior compaction characteristics to those dried by the “high” process type. Radio frequency drying was found to yield granules which produced tablets having slightly inferior tensile strength to tray dried material, although the tablet work of failure values were comparable. The effect of drying technique on the subsequent compaction characteristics was not found to be directly related to the moisture content of the granules.     

Comparison between two types of Artificial Neural Networks used for validation of pharmaceutical processes

Two types of Artificial Neural Networks (ANNs), a Multi-Layer Perceptron (MLP) and a Generalized Regression Neural Network (GRNN), have been used for the validation of a fluid bed granulation process. The training capacity and the accuracy of these two types of networks were compared. The variations of the ratio of binder solution to feed material, product bed temperature, atomizing air pressure, binder spray rate, air velocity and batch size were taken as input variables for training the MLP and GRNN. The properties of size, size distribution, flow rate, angle of repose and Hausner's ratio of granules produced, were measured and used as output variables. Qualitatively, the two networks gave comparable results, as both pointed out the importance of the binder spray rate and the atomizing air pressure to the granulation process. However, the averaged absolute error of the MLP was higher than the averaged absolute error of the GRNN. Furthermore, the correlation coefficients between the experimentally determined and the calculated output values, the corresponding prediction accuracy for the different granule properties as well as the overall prediction accuracy using GRNN were better than using MLP. In conclusion, the comparison of two different networks (MLP, a so-called feed-forward back-propagation network and GRNN, a so-called Bayesian Neural Network) showed the higher capacity of the latter for validation of such granulation processes.