Wet granulation in a batch high shear mixer

This study deals with the wet granulation in a high shear mixer. The experimental apparatus is a laboratory scale ”Lödige” granulator, with a maximum volume of 20 l, equipped with a chopper and a pneumatic spraying system. The main objective of the study is to point out the effect of physico-chemical properties and operating conditions on the growth mechanisms and kinetics in this type of granulation device. Two kinds of alumina with different particle size distributions (alumina SH100 and alumina SH30) were granulated using various Newtonian liquids having different surface tension, viscosity, binder concentration, density, etc. (water, aqueous solutions of polyethyleneglycol or polyvinyl alcohol). Experimental results showed that the granulation process generally proceeds through three distinct growth regimes independent of the nature of the powder, the binder liquid or the operating conditions. However, the transition between different regimes depends on the physico-chemical properties of the solids and liquids, on operating conditions and on the experimental procedure. For the alumina powder used in this study the transition occurs when a degree of liquid saturation of about 68% is reached.     

Switch from single pot to multiphase high shear wet granulation process, influence of the volume of granulation liquid in a pilot scale study

Among the high shear wet granulation equipments used in the pharmaceutical industry, two configurations are current: single pot process for which blending, granulation and drying are performed in the same apparatus and multiphase process that usually associates a mixer granulator and a fluid bed dryer. Pharmaceutical formulations are often developed with regard to a specific industrial apparatus, but production imperatives may require a switch to another type of equipment. In this work, granulation process switch was investigated at pilot scale on a first intention excipient formulation and with two drug substances chosen as model drugs on the basis of their different water solubility. Each one was tested at two concentrations, 1 and 25%. The volume of granulation liquid was first fixed at the same level whatever the granulation equipment and the formulation. In the second part of the study, the effect of the volume of granulation was highlighted. Regardless of the formulation tested, single pot granules, compared to multiphase one, had improved flow properties, compressibility and tablet cohesion but higher sticking phenomenon was observed when tableting. In the second part, the effect of an adjustment of the volume of granulation liquid for horizontal transposition between high shear granulation processes was discussed.     

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     

A study of foam granulation and wet granulation in a twin screw extruder

This research investigated a new technique known as foam granulation for the continuous manufacturing of pharmaceuticals by a twin screw extruder. Six grades of hypromellose were compared as binders in the trials, using two addition methods: foam injection by auxiliary side stuffer feeder and liquid injection directly into the extruder. The produced granules were tested for particle size, Carr compressibility index and characteristic fracture strength. It was found that granulation using foam injection improved powder lubrication inside the extruder and wetting uniformity of the lactose, as well as produced granules having lower Carr indices. © 2012 Canadian Society for Chemical Engineering     

Closing the gap in series scale up of high shear wet granulation process using impeller power and blade design

This paper investigates the use of impeller work combined with an understanding of the significance of the impeller power inflection point during granulation to monitor, control, and scale up high shear wet granulation processes in the pharmaceutical industry. High shear wet granulations were carried out in a series of PMA Fielder granulators (25, 65, 150, and 300-L) with a geometric similar bowl at conditions of constant water addition time and constant tip speed. The results suggested that the granulation process can be effectively scaled up using a linear relationship between the impeller power inflection point (percent of water added at the point where the impeller load starts rising) and the Froude number in PMA Fielder granulator. To close the gap in the series scale up of wet granulation processes, it is desirable to design a granulator at small scale that performs similarly to a full scale commercial granulator such that no variables have to be significantly changed during scale up. A customized 6-L granulator (Fluid Air, Inc.) was designed with a similar bowl geometry as the 300-L Fielder granulator with a specialized blade of lower angle. It is illustrated in this paper that a 6-L granulator can be directly scaled up to a 300-L granulator using constant tip speed and percentage water addition, with the same impeller work and drug product performance. Granulation scale up using the impeller power as the endpoint measurement, combined with a proper impeller blade design can significantly reduce expenditure and time and accelerate the progression of drug product to market, by eliminating stepwise series scale up, and minimizing drug substance requirements.     

Integrating the physics with data analytics for the hybrid modeling of the granulation process

A hybrid model based on physical and data interpretations to investigate the high shear granulation (HSG) process is proposed. This model integrates three separate component models, namely, a computational fluid dynamics model, a population balance model, and a radial basis function model, through an iterative procedure. The proposed hybrid model is shown to provide the required understanding of the HSG process, and to also accurately predict the properties of the granules. Furthermore, a new fusion model based on integrating fuzzy logic theory and the Dempster‐Shafer theory is also developed. The motivation for such a new modeling framework stems from the fact that integrating predictions from models which are elicited using different paradigms can lead to a more robust and accurate topology. As a result, significant improvements in prediction performance have been achieved by applying the proposed framework when compared to single models. © 2017 American Institute of Chemical Engineers AIChE J, 2017     

Integrating process and power grid models for optimal design and demand response operation of giga-scale green hydrogen

Electrolysis-based hydrogen production can play a significant role in industrial decarbonization, and its economic competitiveness can be promoted by designing demand response operating schemes. Nevertheless, the scale of industrial supply plants may be significantly large (on the order of gigawatts), meaning that electricity prices cannot be treated as an input for scheduling problems, that is, the “price taker” approach. This article presents a framework for the optimization of a large-scale, electricity-powered hydrogen production facility considering its integration with the power grid. Using a computational case study, we present an iterative scheme for integrating the process model with a model for power grid optimization and capacity expansion, taking the popular GenX model as an example.     

Growth kinetics and mechanism of wet granulation in a laboratory-scale high shear mixer: Effect of initial polydispersity of particle size

The effect of initial polydispersity of particle size (unimodal versus bimodal distribution) and binder characteristics on the growth kinetics and mechanism of wet granulation was studied. Wet granulation of pharmaceutical powders with initial bimodal particle size distribution (PSD) presented growth kinetics consisting of two stages: fast growth followed by slow growth. The fast stage is controlled by the amount of binder and high probability of coalescence due to the collisions of small and large particles. The second stage is characterized by slow agglomeration of powder mixtures with water content 13.6% v/w, and slow breakage of powder mixtures with water content of 9.9% and 11.7% v/w. The wet granulation of powders with initial unimodal PSD exhibited slow growth kinetics consisting of one stage, since similar particle sizes do not promote agglomeration. The experimental results were better described by a population balance equation using a coalescence kernel that favors growth rate by collision between small and large particles. In general, the probability of a successful collision increased with higher size difference between particles, smaller particle size, and higher binder content.     

AZF工艺与高塔熔体造粒工艺生产尿基复合肥的优缺点

介绍AZF工艺与高塔熔体造粒工艺生产复合肥的过程,从原料调节控制、成本、产品养分等方面进行了比较,认为高塔熔体工艺综合成本较高,新建高塔熔体复合肥项目应慎重。     

浅谈高塔硝基、尿基复合肥转换生产注意事项

介绍硝基、尿基两用复合肥高塔造粒工艺以及硝基工艺、尿基工艺的区别,阐述高塔复合肥生产过程中硝基肥配方与尿基肥配方相互转换生产时各个岗位操作注意事项及管理要求,以最大限度地避免转产时两种系列产品的相互影响造成的质量与安全隐患。     

基于KPLS模型的间歇过程产品质量控制

针对间歇过程所具有的非线性特性,提出了一种基于核偏最小二乘(KPLS)模型的最终产品质量控制策略。利用初始条件、批次展开后的过程数据以及最终产品质量建立了间歇过程的KPLS模型;采用基于主成分分析(PCA)映射的预估方法对未知的过程数据进行补充,实现了最终产品质量的在线预测。为了解决最终产品质量的控制,利用T2统计量确定KPLS模型的适用范围,并作为约束引入产品质量控制问题,提高控制策略的可行性;采用粒子群优化(PSO)算法实现了优化问题的高效求解。仿真结果表明,与基于偏最小二乘(PLS)模型的控制策略相比,所提出的方法具有更高的预测精度,且能有效解决产品质量控制中出现的各种问题。     

料浆转鼓造粒生产S-NPK工艺条件的选择

料浆转鼓造粒生产S-NPK工艺是在料浆喷浆造粒工艺基础上发展起来的,该工艺适合大规模生产,产品养分可调,近年采用此工艺较多。阐述料浆转鼓造粒生产S-NPK各工序工艺条件的选择,并进行了分析,提供了工艺控制指标。由于系统有滞后性,调整要有预见性,做到超前控制才能维持长期稳定生产。     

Equation‐oriented flowsheet simulation and optimization using pseudo‐transient models

Tight integration through material and energy recycling is essential to the energy efficiency and economic viability of process and energy systems. Equation‐oriented (EO) steady‐state process simulation and optimization are key enablers in the optimal design of integrated processes. A new process modeling and simulation concept based on pseudo‐transient continuation is introduced. An algorithm for reformulating the steady‐state models of process unit operations as differential‐algebraic equation systems that are statically equivalent with the original model is presented. These pseudo‐transient models improve the convergence of EO process flowsheet simulations by expanding the convergence basin. This concept is used to build a library of pseudo‐transient models for common process unit operations, and this modeling concept seamlessly integrates with a previously developed time‐relaxation optimization algorithm. Two design case studies are presented to validate the proposed framework. © 2014 American Institute of Chemical Engineers AIChE J 60: 4104–4123, 2014     

Learning surrogate models for simulation‐based optimization

A central problem in modeling, namely that of learning an algebraic model from data obtained from simulations or experiments is addressed. A methodology that uses a small number of simulations or experiments to learn models that are as accurate and as simple as possible is proposed. The approach begins by building a low‐complexity surrogate model. The model is built using a best subset technique that leverages an integer programming formulation to allow for the efficient consideration of a large number of possible functional components in the model. The model is then improved systematically through the use of derivative‐free optimization solvers to adaptively sample new simulation or experimental points. Automated learning of algebraic models for optimization (ALAMO), the computational implementation of the proposed methodology, along with examples and extensive computational comparisons between ALAMO and a variety of machine learning techniques, including Latin hypercube sampling, simple least‐squares regression, and the lasso is described. © 2014 American Institute of Chemical Engineers AIChE J, 60: 2211–2227, 2014     

新型高强度单组分环氧树脂胶粘剂的研制

采用新工艺制备了一种新型高强度单组分环氧树脂胶粘剂。实验结果表明,新型环氧树脂体系具有良好的力学性能、疏水性及耐热性。     

高剪切混合器研究与应用进展

高剪切混合器作为一种能量密集型的过程强化手段,具有剪切速率高、局部能量耗散率高的特点,可以实现均质、乳化、溶解、分散、悬浮、结晶、破碎、反应等过程的强化,但尚缺少理性设计方法的系统研究。本文简述了高剪切混合器分类、工作模式,总结了操作参数、结构参数、物性参数等对高剪切混合器的流动与返混特性、微观混合特性、乳化和液液传质特性、气泡分散与气液传质特性、固体破碎与分散特性等的影响规律,简介了高剪切混合设备的工业实用案例;进而提出了该领域有待深入拓展的研究方向,包括高剪切混合器能量效率的提升途径、多相体系下高剪切混合器模型的建立方法、高剪切混合器与其他单元操作耦合规律、高剪切作用与外场协同强化机理、基于高剪切混合器的过程强化工艺优化等。     

催化湿式氧化法处理焦化废水的分析

概述了焦化废水水量大、成分复杂、污染物浓度高等水质特点和传统焦化废水处理方法及其缺陷，提出应用催化湿式氧化技术处理焦化废水这一新途径。并就技术和经济方面对催化湿式氧化技术处理焦化废水进行了分析，说明利用该技术处理焦化废水不仅技术上可行而且具有较好的综合效益。指出了催化湿式氧化技术在工业化过程中面临催化剂溶出和反应设备材质要求高等问题。     

Multistream heat exchangers: Equation‐oriented modeling and flowsheet optimization

Multistream heat exchangers (MHEXs), typically of the plate‐fin or spiral‐wound type, are a key enabler of heat integration in cryogenic processes. Equation‐oriented modeling of MHEXs for flowsheet optimization purposes is challenging, especially when streams undergo phase transformations. Boolean variables are typically used to capture the effect of phase changes, adding considerable difficulty to solving the flowsheet optimization problem. A novel optimization‐oriented MHEX modeling approach that uses a pseudo‐transient approach to rapidly compute stream temperatures without requiring Boolean variables is presented. The model also computes an approximate required heat exchange area to determine the optimal tradeoff between operating and capital expenses. Subsequently, this model is seamlessly integrated in a previously‐introduced pseudo‐transient process modeling and flowsheet optimization framework. Our developments are illustrated with two optimal design case studies, an MHEX representative of air separation operation and a natural gas liquefaction process. © 2015 American Institute of Chemical Engineers AIChE J, 61: 1856–1866, 2015     

高温快速萃取技术和转台过滤机的应用

1991年投产的 1.5万 t P2 O5/ a装置 ,经采用高温快速萃取技术与 78m2 转台过滤机 ,并通过实践摸索过程 ,采取若干技术措施 ,解决了滤盘结块 ,滤布需频繁更换等问题。技改后使装置生产能力达 7万 t P2 O5/ a,滤布使用寿命延长至 2 0～ 2 2天 ,磷石膏 w(P2 O5水 )从 0 .4 %～ 0 .6 %降低到 <0 .1%。