Scale-up of binder agglomeration processes

This review article describes scale-up of batch and continuous granulation processes where liquid binder is added to fine powder in order to form a granular product. The technical goal of scale-up is to maintain similarity of critical product attributes as the production scale and/or throughput of a manufacturing process is increased. This paper provides a framework for scaling-up that considers critical process transformations in relation to the desired product attributes. A similar approach can be taken in developing process control strategies. In any agglomeration process, transformations can be used to describe how raw materials (typically fine powders and liquid binders) are converted into a granular product. Often the critical product attributes are characterized on the scale of individual granules (e.g., size, shape, porosity, mechanical strength, etc.). On the other hand, industrial scale-up requires predictive relations for the sizing, design and operation of process equipment. Considering scale-up on the basis of transformations is one way to link the macro-scale equipment decisions with micro-scale product attributes. This approach can be applied to the scale-up of batch and/or continuous granulation processes as well as transitioning from small batch prototypes to continuous production circuits.     

Performance comparison of batch and continuous flow surface aeration systems

The oxygen transfer rate and the corresponding power requirement to operate the rotor are vital for design and scale-up of surface aerators. The aeration process can be analyzed in two ways such as batch and continuous systems. The process behaviors of batch and continuous flow systems are different from each other. The experimental and numerical results obtained through the batch systems cannot be relied on and applied for the designing of the continuous aeration tank. Based on the experimentation on batch and continuous type systems, the present work compares the performance of both the batch and continuous surface aeration systems in terms of their oxygen transfer capacity and power consumption. A simulation equation developed through experimentation has shown that continuous flow surface aeration systems are taking more energy than the batch systems. It has been found that batch systems are economical and better for the field application but not feasible where large quantity of wastewater is produced.     

Scale-up in the 4th dimension in the field of granulation and drying or how to avoid classical scale-up

In the pharmaceutical industry, the production of granules is based on a batch concept. This concept offers many advantages, as a batch can be accepted or rejected. However, the scale-up of the batch size may lead to problems. The variety of the equipment involved does not facilitate the scale-up process and the capital invested in space and equipment is high. An alternative approach is the use of a continuous process. However, continuous processes have the disadvantage among others that the batch size is not well defined. Thus, a special quasi-continuous production concept was developed, taking into account the advantages of a batch type and a continuous process. This concept was developed in cooperation with the Institute of Pharmaceutical Technology of the University of Basel, Glatt CH-4133 Pratteln and F. Hoffmann-La Roche, CH-4070 Basel. The equipment allows to implement a “Just in Time Production Concept” as a large batch B consists of n subunit (SU) batches b, i.e. B=nb. The subunit batch b corresponds to, e.g. 7-kg material for the production of pharmaceutical granules for further processing such as tabletting. At the Roche production site, this novel process equipment was used to manufacture batch sizes B with n=10, n=100 and so far up to n=600 subunits. This leads to an optimal use of capital invested in GMP space and equipment. The difference to the classical scale-up is the following: with classical scale-up, the dimensions of the equipment x, y, z is enlarged and the process time is more or less kept constant. With this novel concept, the dimension x, y, z of the equipment is kept constant and the process is repeated in the 4th dimension “n times”. Thus, for the scale-up in the 4th dimension, i.e. in the time, the equipment needs to show a “self-cleaning” property and appropriate formulations. The novel concept is of special interest, as the quality of the product is not changed during scale-up.     

A narrow size distribution on a high shear mixer by applying a flux number approach

High shear granulation is a common technology for particle size enlargement, but generally the product properties are badly affected by the broad size distribution generated in the process. A recently published approach by Michaels et al. [J.N. Michaels, G. Wang, L. Farber, K.P. Hapgood, J.H. Chou, S. Heidel, and G.I. Tardos, 2006, One-dimensional scale-up of high-shear granulators, Paper 243c, World Congress Particle Technology 5, Orlando (FL)] employs low binder solution spray rates and long granulation times, whilst the solids are kept in roping flow, to avoid coarse formation. The present work applies this approach to a two-component binder system with a dry powder gum and water spray as activation agent. Similarities with fluidised bed granulation and coating processes are explored. The work shows that indeed narrow size distributions of fine granules can be achieved with ease. Dimensionless numbers for spray fluxes are useful to identify operating regimes and to steer optimisation efforts. Comparison of flux numbers for different systems shows that they are not useful (yet) for detailed product and process design. Further work on material-specific quantities controlling nucleation and growth, e.g. particle wetting, is recommended.     

Investigation and scale-up of hot-melt coating of pharmaceuticals in fluidized beds

This study was performed to investigate and scale-up the hot-melt coating process in fluidized beds. A series of well-designed experiments was carried out in a pilot scale unit with 20 kg product capacity to investigate the effects of process variables on the efficiency of the coating of Cefuroxime Axetil with stearic acid. Results showed that the efficiency is at the highest when the fluidization air flow rate is adjusted by considering the changes in the amount of materials present in the unit as well as the changes in the terminal velocities of particles during the process.With the objective to scale-up the hot-melt coating process from pilot to production scale, a dynamic thermodynamic model based on conservation equations of mass and energy was developed. Predictive accuracy of the model was assessed by applying it to the pilot scale unit and comparing its predictions with the online measurements taken on the same unit. Results showed that the predictions of the model agree well with the measurements. Utilizing this model and taking several experiments performed in the pilot scale unit as a basis, scaling up of the hot-melt coating process was carried out. Comparisons of the model predictions with the measurements taken on the production scale unit (200 kg product capacity) revealed that the model is able to reproduce the product attributes and the outlet air temperatures across scales. Therefore, it proves to be a promising tool that can be used in the scale-up of the hot-melt coating processes in fluidized beds.     

光化学微反应技术的基础及研究进展

光化学转化是有效利用光能实现化学反应的重要途径,微反应技术为提高其过程效率提供了一个强有力的平台。本文首先指出微反应器相比于传统釜式光反应器,在光强分布、过程放大、光能利用效率等诸多方面存在明显的优势,能够实现光化学反应过程的高效强化。简要地介绍了光化学转化及光化学微反应技术的基本特征,然后系统地综述了光化学微反应器的设计构建及其在有机合成、聚合等方面的应用,并详细介绍了自动化控制的光化学微反应系统及应用。重点介绍了微反应技术在紫外光、可见光辐照下的光化学合成进展及其过程放大。最后,对光化学微反应技术的研究进展进行总结,并对其发展趋势进行了展望。     

Product Engineering am Beispiel extrudierter Instantpulver

Product Engineering in the Case of Extruded Instant Powders . Starch based instant powders are usually produced by cooking/gelatinizing in an excess of water with subsequent drying and milling. Important product attributes are the specific weight and the instant properties of the powder, as well as the taste, the viscosity, and the mouth-feel of the reconstituted gel. Cooking extrusion is an alternative energy saving process. Process development usually takes a long time and proves expensive due to the large number of different process parameters and their possible combinations. For two exemplary products it is demonstrated how the screw configuration and the target range of process parameters can be defined by statistical trial design. Final optimization (?fine tuning”?) and scale-up assure efficient process design according to product needs.     

污水处理运行模式对好氧颗粒污泥特性的影响

研究了运行模式的改变对好氧颗粒污泥优势丝状菌种类,以及对污泥特性所产生的影响.结果表明,序批式活性污泥法反应器(SBR)中出现大量外伸型丝状菌Type 021N,但并未阻碍污泥的颗粒化,且随着絮体污泥颗粒化进程的推进,其对污泥沉降性的影响也在逐步减小,最终得到平均粒径为0.75 mm、污泥容积指数为43 mL/g的成熟...     

Profitability as a criterion of batch process control design

Batch processes have in some cases many advantages in comparison with continuous processes even though continuous processes are becoming common.

The main disadvantages of batch processes are the discontinuous usage of raw materials and energy as well as the discontinuous production thus causing difficulties in power plant and other continuous processes connected with the batch process in question. If there are several parallel process units, difficulties can arise with parallel process unit sequencing and product quality equalization. However, with the aid of computer control these and other disadvantages are eliminated or minimized so that total automation of batch processes is possible.

In this paper the basic principles of batch process control design are considered, with particular emphasis on the economic justification criterion. As an example, a computer control design of sulphate batch digesters is considered. This approach is based on more than 20 implementations of batch process automation.     

基于能量等效的双转子连续混炼机混炼段相似放大研究探讨

根据双转子连续混炼机自身特性和等效平均停留时间、等价转子顶部剪切速率的原则,以能量等效为衡量混合效果的准则,提出双转子连续混炼机混炼段相似放大设计的流程及其理论模型。在该模型确定的转子转速和喂料速率下,利用Polyflow软件模拟了机筒内径分别为30 mm和100 mm的双转子连续混炼机混炼段和卸料段内的流场特征,以能量等效为指导准则,通过对流场特征和混合效果进行分析,对所提出的相似放大设计理论模型进行了验证。     

Granulation time in fluidized bed granulators

Size enlargement of particles in fluidized bed granulation involves mixing of particles with a binder liquid to form larger wet granules and drying them to form dry granules. Identification of the time for completion of granulation process is critical as further fluidization of dry granules is providing extra energy for their attrition. Monitoring the bed pressure drop and bed temperature of a batch fluidized bed granulator with time can provide information on the time for completion of the granulation process. Experimental observations on granulation time and size of granules in a lab-scale batch fluidized bed granulator are presented. Model based equations are developed for the estimation of granulation time and size of granules.     

Optimal control and operation of drum granulation processes

Process optimisation and optimal control of batch and continuous drum granulation processes are studied in this paper. The main focus of the current research has been: (i) construction of optimisation and control relevant, population balance models through the incorporation of moisture content, drum rotation rate and bed depth into the coalescence kernels; (ii) investigation of optimal operational conditions using constrained optimisation techniques; (iii) development of optimal control algorithms based on discretized population balance equations; and (iv) comprehensive simulation studies on optimal control of both batch and continuous granulation processes. The objective of steady state optimisation is to minimise the recycle rate with minimum cost for continuous processes. It has been identified that the drum rotation-rate, bed depth (material charge), and moisture content of solids are practical decision (design) parameters for system optimisation. The objective for the optimal control of batch granulation processes is to maximize the mass of product-sized particles with minimum time and binder consumption. The objective for the optimal control of the continuous process is to drive the process from one steady state to another in a minimum time with minimum binder consumption, which is also known as the state-driving problem. It has been known for some time that the binder spray-rate is the most effective control (manipulative) variable. Although other possible manipulative variables, such as feed flow-rate and additional powder flow-rate have been investigated in the complete research project, only the single input problem with the binder spray rate as the manipulative variable is addressed in the paper to demonstrate the methodology. It can be shown from simulation results that the proposed models are suitable for control and optimisation studies, and the optimisation algorithms connected with either steady state or dynamic models are successful for the determination of optimal operational conditions and dynamic trajectories with good convergence properties.     

好氧颗粒污泥的快速培养以及胞外多聚物对颗粒化的影响研究

采用普通活性污泥、部分好氧颗粒污泥和部分厌氧颗粒污泥分别作为接种污泥培养好氧颗粒污泥。在操作条件相同的情况下比较三者颗粒化的过程与完成时间。同时,研究胞外多聚物(EPS)对好氧污泥颗粒化的影响。结果显示,预先投加部分好氧颗粒污泥可以大大缩短好氧颗粒污泥的形成时间,胞外多聚物与污泥的颗粒化有密切联系。     

An integrated system of a microreactor with a Taylor–Couette reactor for 2,2′-dibenzothiazole disulfide synthesis

An integrated microreaction system of a microreactor with a Taylor–Couette reactor (TCR) for continuous synthesis of 2,2′-dibenzothiazole disulfide has been developed, so as to improve the process efficiency and the stability with solid product generation compared with the current batch process. The homogeneous oxidation with hydrogen peroxide catalyzed by phosphotungstic acid was applied. In the microreaction system, two feedstocks can be rapidly mixed through the microreactor; stable particle flow ability and high conversion can be achieved through the TCR, due to the flow characteristics of high shear stress and limited back-mixing. Under the conditions of stable operation, the conversion can reach over 90%. The purity of the product is over 99%. The space–time yield can reach 160 g L⁻¹ h⁻¹, which is much higher than that in the batch reactor. The microreaction system is stable for long-term running, which provides an effective design strategy for continuous flow processes with solid generation.     

Breakage in granulation: A review

The study of breakage in granulation is important from a process and from a product quality perspective. Breakage is considered an important rate process in granulation, and plays roles in granule homogeneity and strength. Understanding this rate process has important implications in the design and control of the granulation process. From a product perspective, the study of breakage has important implications for the subsequent processing, transport, handling and final use of granular products. Breakage behaviour of granules can be a strong signature of the consistency of properties between nominally identical granular products. This paper reviews the study of breakage from the process scale down to the single granule and sub-granule scale, discussing largely experimental results complemented with some modelling results.     

化学产品过程开发实验平台--公斤实验室的建设和应用

以化工产品设计和过程开发为导向,建立了一个化工产品过程开发实验平台--化工产品公斤实验室Kilo-lab.该公斤规模试验装置可进行反应、结晶、分离、提纯等系列产品的开发过程,研究了流程装置集成和柔性生产系统的规律和特征,为小批量、多品种、高附加值化学产品快速响应市场的变化和需求,以及过程开发的工业化放大提供理论和实验依据.     

Scaleup of wet granulation processes: science not art

Significant advances have been made in the last decade to quantify the process of wet granulation. The attributes of product granules from the granulation process are controlled by a combination of three groups of processes occurring in the granulator: (1) wetting and nucleation, (2) growth and consolidation and (3) breakage and attrition. For the first two of these processes, the key controlling dimensionless groups are defined and regime maps are presented and validated with data from tumbling and mixer granulators. Granulation is an example of particle design. For quantitative analysis, both careful characterisation of the feed formulation and knowledge of operating parameters are required. A key thesis of this paper is that the design, scaleup and operation of granulation processes can now be considered as quantitative engineering rather than a black art.     

Aspects of granulation in the chemical industry

In general, the intention of granulation processes in chemical industry is to achieve certain product properties. The requirements are specific for each product and cover application properties, process and handling properties, safety characteristics and marketing features. However, selection of an agglomeration process and equipment to be used for production is usually influenced by other factors than product properties: Options are often limited, because equipment which was used for another product is available, or the granulation process has to fit in the total production process.In granulation, only few information about scientifically based differentiation between alternative granulation processes such as mixer agglomeration, compaction or fluidized bed granulation and classification of different apparatus can be found in literature.Therefore, one focus of industrial investigations in granulation is on comparison of different processes and assessment of different types of apparatus. Here, an example for a comparison of different granulation processes with respect to product properties will be shown.     

Particle population modeling in fluidized bed-spray granulation—analysis of the steady state and unsteady behavior

Owing to its intensive mass and heat transfer ratios and its coupling of the process stages of drying, shaping and homogenization as well as classification, continuous fluidized bed-spray granulation drying has gained acceptance as a thermal treatment process for granular solids. In this study, a balance of the particle populations is completed for a continuous fluidized bed-spray granulation with external classification. Thus, it ought to be possible to describe the particle size distributions changing over time in the fluidized bed and in the product flow [Powder Technol. 82 (1995) 37; H. Uhlemann, L. Mörl, Wirbelschicht-Sprühgranulation, Springer Verlag, 2000, ISBN 3-540-66985-X.].