Characterisation of fluidised bed granulation processes using in-situ Raman spectroscopy

This report with recommendations is the result of an expert panel meeting on PAT applications in food industry that was organized by the M3C Section of the European Society of Biochemical Engineering Science (ESBES) at the 10th ESBES Symposium. The aim of the panel was to provide an update on the present status of the subject and to identify critical needs and issues for wider applications of PAT in food industry. A brief description of the current state-of-the-art and industrial uptake of the methodology is provided in this report. It concludes with a number of recommendations to facilitate further developments and a wider application of PAT in food industry. Process Analytical Technologies (PAT) [1] (European Medicines Agency EMA-FDA pilot program for parallel assessment of Quality by Design applications; Document EMA/172347/2011) have been extensively discussed in literature, particularly with respect to (bio)pharmaceutical process modelling, monitoring and control [2]. Table 1 provides an historic overview of the PAT development in the context of food applications. Although successful applications within food industry are increasingly being reported [3, 4], the session on PAT in food industries at the ESBES-IFIBiop 2014 in Lille highlighted significant challenges and opportunities for further development in this area. This position paper briefly reviews the current state-of-the-art, industrial needs and opportunities as well as scientific challenges to be addressed in order to extend the use of PAT methodology in the food industries. Currently, quality and safety control are still based mainly on discontinuous analysis with traditional analytical methods in the lab or, at best, at-line measurements. This is no longer sufficient to fulfill the needs of the food industry. Due to higher safety and quality standards and demands and high throughput of production facilities, the number of samples to be analyzed is increasing. Rapid analysis methods and PAT are required to address these needs along the complete production chain leading to a better understanding and control of raw materials, intermediate products in the production process as well as the final products to be packaged and delivered. The goal is to achieve real time analysis in order: • to avoid usage of any out-of-specification raw material and to detect adulteration, substitution, tampering and counterfeiting leading to non-authentic products; • to be able to intervene and stop/change processes in order to secure the target quality; • to assess the final quality to avoid out-of-specification products being packaged and shipped, thus leading to undesirable customer dissatisfaction and costs associated with the resolution of complaints. Over a hundred years ago (on May 22nd, 1913) the first patent on a PAT device ("Pfeiffenanalysator" for measuring the ratio of H2 and N2 gas for ammonia synthesis) was granted to Paul Gmelin from Badische Anilin- und Soda-Fabrik, BASF (Patentschrift Nr. 281157, Klasse 42/. Gruppe 4). Since then, PAT found broad application in chemical industry, which is dominated by highly automated, continuous processes. Today in chemical processes, such as the synthesis of isocyanates, e.g. hexamethylendiisocyanate (HDI), typically 60-130 PAT measurements are collected. In contrast, in sectors like (bio)pharmaceutical or food industry, the application of PAT is significantly less frequent today, especially, in terms of on-line analytics, where the measurement takes place in or close to the production step (or unit operation). One reason for this is the reduced degree of automation of the processes in these industries, which are dominated by unit operations, single production steps consecutively executed after each other, resulting in production batches. Analytics of a production batch takes place mostly off-line in analytical laboratories during hold-up times of the process intermediate between the different unit operations. Regulatory requirements represent an equally important driver for extensive online analytics. With the 2004 FDA's Quality by Design initiative, regulatory agencies demand systematic risk based process development and understanding of the processing space. This also allows for flexible process adjustments within the explored space for producing the desired product quality. In order to achieve the required understanding, more extensive analytical data is required, ideally obtained in-time on raw materials, process intermediates and ideally also on product quality attributes. In food industry, where typically high product titers are obtained, product analytics is sometimes possible by in-line measurements, such as spectroscopy (section 4). In biopharmaceutical processes, product titers are usually very low, the products are proteins with high molecular weight, and quality attributes are challenging to analyse. In these situations, online sampling with automated sample preparation and analytics may open up a solution [5]. But, identifying and implementing analytical methods, which are fast enough for delivering results on product quality attributes (e.g. protein glycosylation) in time, during the unit operation for allowing process modulation, remains a challenge. The overall typical goals in industry are high safety, high and stable product quality, high yield, low consumption of resources (materials, energy, room, time, and people), reduced influence of variability in raw materials as well as an increased shelf life of products which holds also in food processes. However, compared to the chemical and biopharmaceutical industries, food industry has to deal with certain characteristics, which renders PAT a formidable challenge in this context. The characteristic features in food industry are: • Raw materials are not pure substances: they are complex combinations of pure substances with varying compositions • Raw materials are soft, variable size, fragile and slippery • Physical properties of raw materials depend heavily on temperature, pressure, moisture and harvesting, and storage conditions • Raw materials undergo usually a phase transformation during processing and hence change their physical properties during processing • Micro processes (physical, (bio)-chemical, microbiological) are frequently not known • Highly perishable products. Here the challenge is to produce good quality, which maintains for a long time (shelf life) • High demand for hygiene These characteristics lead to a challenge for the application of sensors in the food industry. For important quality and process variables, such as sensory assessment, micro flora or spoilage, reliable and robust sensors are not yet available. Moreover, the sensors which are available are typically used only in isolated applications and frequently provide insufficient reliability. They are often not integrated in a common data management infrastructure. The materials of construction do not always consider suitability of contact with food and the solutions developed within advanced research projects frequently demand high care and maintenance. One reason why PAT is not as common as in other areas is that in food industry knowledge from various subject areas is necessary (such as physics, chemistry, biology, mathematics, informatics, engineering, nutritional science). For unit operations mathematical models are available in principle, but frequently they are too complicated to adapt. One of the biggest challenges in food industries is the dynamic nature of the processes. Changes in geometry, porosity, microstructure, solubility as well as mass and energy transfer coefficients must be addressed. Mostly gradients of temperature and moisture have to be considered as well as changes in kinetic parameters during process run. End product qualities like color, smell and 'brokens' also strongly influence the process. Therefore, food processes can be considered to be significantly more complex then chemical and bio-pharmaceutical processes. To achieve more stable processes PAT applications are necessary to check the quality of the raw and processed materials and their relationship to each other. If the quality is changing, then control actions resulting in online parameter changes are required in order to maintain constant product quality. Measurement systems are required, which guarantee that the process is in accordance with recipe and formulation. Furthermore, disturbances must be compensated for using control actions to reduce process variability and to conform to food regulations. As Glassey [6] argues, PAT methodology can aid in product design and testing as well as in ensuring full compliance with the HACCP and ISO 22000:2005 requirements during processing. As demonstrated below, PAT methodologies have the potential to aid the identification of critical control points and their critical limits, their effective monitoring and control, but also effective communication with suppliers and customers. Documentation which requires measurements of important variables is especially important so that traceability can be guaranteed. Here PAT has to deliver the corresponding measurement systems. Clearly a high demand for PAT in food industry is evident as is the need for further developments in the science and technology that help address the specific challenges posed by the characteristics of the food industry highlighted above. The complexity of raw materials that are typically soft and easily damageable is arguably one of the major scientific and technological challenges in food industry. During storage and processing the quality of such raw materials can decline due to oxidation processes, pressure and temperature effects. In addition, the visual impression of the final product (i.e. its appearance) is much more important than in other industries due to the fact that this will influence the purchase decision of the consumer. During the whole processing from raw material to the storage of the final product, hygiene is of utmost importance. Therefore non-invasive sensor systems are required in these applications. Measurement systems based on optical principles are particularly suitable from this perspective. Such measurement systems, including near infrared (NIR), Raman and fluorescence spectroscopy as well as computer-assisted image-based systems, potentially have a number of advantages in food process supervision and automation. Spectroscopic methods and imaging devices are well suited for PAT purposes because they are fast, non-destructive, provide multiple chemical information, allowing remote in-process analysis via fiber optics or instruments mounted directly on-line. Fluorescence spectroscopy is the most sensitive spectroscopic technique. Recently, many applications have been developed using fluorescence techniques [3, 7, 8]. Raw materials, the supervision of processing as well as product quality and the contamination of the equipment can be monitored by fluorescence. For example, Everard et al. [3] presented a method for detection of fecal contamination on spinach leaves. They coupled three hyperspectral imaging (HSI) configurations with two multivariate image analysis techniques and compared fluorescence imaging in the visible region with ultra violet and violet excitation sources, and reflectance imaging in the visible to near-infrared regions. They showed, that both fluorescence configurations had 100% detection rates for fecal contamination up to 1:10 dilution level and violet HSI had 99% and 87% detection rates for 1:20 and 1:30 levels, respectively. Everard et al. emphasized that on-line detection of fecal contamination on leaves has the potential to reduce the cases of food borne illnesses and their associated costs. A similar approach is presented by Lee et al. [7] where bovine faeces on Romaine lettuce and baby spinach leaves were investigated. They pointed out that two-band ratios using bands at 665.6 nm and 680.0 nm for lettuce and at 660.8 nm and 680.0 nm for spinach effectively differentiated all contamination spots applied. Grote et al. [8] described a fluorescence measurement technique to monitor a sourdough fermentation process. For the prediction of pH value and acidity during rye sourdough fermentations they applied partial least squares regression and principal component regression models for prediction and compared them with an evaluation where principal component analysis was combined with artificial neural networks. Depending on process operation and evaluation technique the average percentage root mean square errors of prediction for pH values were between 2.5 and 5.1%. For the prediction of the acidity level, the best results were between 6.0 and 8.1%. Liu et al. [9] used the Hoffman reaction to convert acrylamide to a compound which shows strong fluorescence emission at 480 nm. They showed good correlation of acrylamide in the range of 0.015 μg/mL to 20 μg/mL. Using this technique the food security will be increased. A fluorescence imaging device to detect deli residues on deli slicers were used by Beck et al. [10] processing four cheeses and four processed meats. The authors suggested that a fluorescence imaging device can be applied for routine use even in delicatessens. Fig. 1 clearly shows that the application of fluorescence for the monitoring of food processes increased from less than 10 before 2003 to more than 60 a year since 2013. This figure includes all papers from a search containing the key words "Food" and "Fluorescence". Although most of these papers describe laboratory applications rather than industrial PAT applications, they indicate potential future applications in this technology in food industry. Number of published papers obtained from the Scopus database searching for the words "Food" and "Image analysis" or "Raman" or "Near infrared spectroscopy" or "Fluorescence spectroscopy". Raman spectroscopy can only be applied if no fluorescence occurs in the corresponding excitation range. He et al. [11] applied the surface enhanced Raman scattering spectroscopy to detect banned food additives, such as Sudan I dye and Rhodamine B in food, Malachite green residues in aquaculture fish. They concluded, that Raman spectroscopy and chemometric evaluation techniques can be used to identify banned food additives to ensure food safety. Ilaslan et al. [12] presented a method based on Raman spectroscopy to provide a rapid method for evaluating the quantitative analysis of glucose, fructose, and sucrose in soft drinks. Wang et al. [13] applied a Raman spectrometer as a process analyzer to monitor the wine fermentation. They demonstrated that sugar, ethanol and glycerol can be measured on-line with high correlation (higher than 0.98) to the HPLC reference measurements. Nache et al. [14] investigated Raman spectra from pork meat to monitor the early postmortem lactate accumulation and pH decline. They suggested that the locally weighted regression applied to the standard normal variate (SNV) normalized Raman spectra provide one of the most accurate and robust models with a cross-validated coefficient of determination (r2cv) of 0.97 for pH and lactate, a cross-validated root mean square error (RMSECV) of 4.5 mmol/kg for the lactate prediction and 0.06 pH-units for the pH prediction. These results demonstrate significant potential of combining chemometrics and Raman spectroscopy for on-line meat quality control applications. Fig. 1 shows the number of papers recorded in Scopus (search words "Food" and "Raman"). Compared to fluorescence, the number of papers describing Raman spectroscopy is twice as high in recent years with a significant rate of increase, demonstrating the increasing interest in this method for food process monitoring. Computer vision systems enable one of the main aspects of consumer preference – the appearance of a product – to be inherently considered. Therefore, computer vision systems for the supervision of food processing also gained importance over the years. An overview of several examples is given by Sun [15]. Especially the supervision of food drying processes is discussed by Aghbashlo at al. [16]. They pointed out that there is a large unexploited potential in the image data captured during various food processing operations. More informative feature extraction algorithms or novel pattern recognition procedures have to be developed. Paquet-Durand et al. [4] described a system for the supervision of the baking process. They demonstrated, by using the Viola–Jones-algorithm as well as neural networks, that the pastry can be identified and the volume increase as well as color development can be monitored. To detect defective apples Zhang et al. [17] used a computer vision system, which was combined with an automatic lightness correction system. For 160 samples they showed a 95% overall detection accuracy. For the evaluation they used a weighted relevance vector machine classifier. Fig. 1 shows the number of papers over time from Scopus searching for "Food" and "Image analysis". Here the applications start earlier compared to the spectroscopic methods, the number of applications per year is higher than in the case of spectroscopic applications; except in the year 2014, where more reports of Raman applications were published. Moreover imaging systems using visible and NIR region are available to perform quality checks based on the spectroscopic information derived from each point in the image. One example is the on-line analysis of the widely varying fat distribution in salmon for sorting purposes [18]. Near infrared (NIR) is a well-established method for rapid analysis of food raw materials and products [18], either on-/in-line, at-line or off-line. In the lab or at-line multiple components such as fat, protein, moisture and many more, can be analyzed without any sample preparation in all kinds of liquid, solid and semi-solid samples. Raw materials can be verified for identity and further characterized regarding composition already in the goods reception. The composition, freshness and adulteration of edible oils [19], e.g. olive oil [20], can be analyzed rapidly before a truck is unloaded. Many other sample types like meat, grains, flour, dairy products [21] and others can be analyzed. Even mixtures like vitamin premixes can be analyzed to make sure that the correct material was delivered and can be used in production. There are several approaches and technologies for PAT available, ranging from simple filter based devices over dispersive diode array spectrometers to Fourier-Transform (FT)-NIR instruments. Samples can be analyzed in-line by fiber optic probes or by contactless systems (Fig. 2). Smaller instruments can be directly attached to pipes, chutes or in other installations. A) NIR reflection probe in a fluid bed dryer. (B) Probe head for contactless measurement of grain and other solids. Applications cover a broad range from a simple monitoring of moisture content of a product on a conveyor belt to more complex control situations. In dairy industry there are demands to control milk powder production by monitoring the feed of the spray tower and the powder after fluid bed drying. Other important production steps to control are the standardization of milk, cream, whey and concentrates [22]. In frying processes with big volumes of oil an in-line monitoring of the oil quality with regards to acid value, anisidine value and the content of polar and polymerized components [23] are of particular interest. Another example of high volume processes where monitoring of protein, moisture and ash is important is the milling of grain to flour and the production of cereals of any kind. Finally there are more and more fermentation processes controlled by in-line NIR to optimize the conditions and follow the feeding and consumption cycles during biomass buildup [24]. In 2013 roughly 120 papers were published, however the recent increase is not as steep as in the case of Raman spectroscopy (Fig. 1). The economic benefits due to PAT can be attributed to higher product quality and yield as well as decreased product variation. This will reduce the overall production costs significantly and increase competitiveness. Furthermore, the knowledge and understanding of the process will increase. However, the level of automation in industrial food processes is significantly lower compared to the chemical and pharmaceutical processes. This is partly due to the complexity of food processes. On the other hand, the lack of reliable sensor systems to determine important process parameters and variables contributed to this in the past. Sensors represent a fundamentalpart of all automation systems, although they only represent a part of the requirements for wider application of PAT in food industry. The areas of further development and recommendations enabling more extensive use of the PAT within this industry also include: • Further industrial case studies and wider dissemination of the positive impact of reliable sensor technology in raw material and product quality as well as process monitoring. • Operational and maintenance requirements of sensor technologies will remain a significant aspect of future sensor technology uptake in this industry. • Data management and analysis software will play a significant role in extending the PAT application within the food industry. Platform solutions, preferably supporting wireless data transfer, at competitive pricing levels are required. • Cost benefit analysis studies are particularly important given the business drivers of this industry. • The impact of PAT is likely to be more pronounced in the new processes, although it is important to continue to encourage the application of PAT approaches within established food processes to enhance the process economics and compliance with the standards ensuring safe food supply chains. • PAT can significantly contribute to the stringent traceability and documentation requirements, although issues of compatibility and data standardization will impact upon data management systems employed by the companies within the supply chain. The authors declare no financial or commercial conflict of interest.

A novel setup, combining two spectroscopic techniques, laser induced breakdown spectroscopy (LIBS) and Raman spectroscopy in a hybrid unit, is described. The work presented herein is part of a broader project that aims to demonstrate the applicability of the hybrid LIBS-Raman unit as an analytical tool for the investigation of samples and objects of cultural heritage. The system utilizes a nanosecond pulsed Nd:YAG laser (532 nm) for both LIBS and Raman analysis. In the Raman mode, a low intensity beam from the laser probes the sample surface and the scattering signal is collected into a grating spectrograph coupled to an intensified charge-coupled device (ICCD) detector, which records the Raman spectrum. In the LIBS mode a single high intensity pulse from the laser irradiates the sample surface and the time- and spectrally-resolved emission from the resulting laser ablation plume yields the LIBS spectrum. The use of a non-gated CCD detector was found to produce similar quality data (in terms of S/N ratio and fluorescence background) in the Raman mode, while in the LIBS mode spectral features were clearly broader but did not prevent identification of prominent atomic emission lines. Several model pigment samples were examined and the data obtained show the ability of the hybrid unit to record both Raman and LIBS spectra from the same point on the sample, a clear advantage over the use of different analytical setups.

Fluidized Bed Dryers — Recent Advances

In Victoria, Australia, brown coal is utilised as a major source of energy for the power generation industry. Victorian and South Australian brown coals have a very high moisture content and therefore, the efficiencies of power generation in traditional pulverised fuel fired furnaces are low. Fluidised beds offer a number of advantages over conventional furnaces, leading to improvements in efficiency and environmental impact. A disadvantage with implementing fluidised bed technology is the issue of scale-up. Fluidised bed behaviour can alter significantly with changes in scale, because of their strong dependence on the bed hydrodynamics. Hence, there is a need to accurately model bed behaviour to ensure that the effect of changes in scale are well understood and will not become costly and time consuming. Computational Fluid Dynamics (CFD) techniques can be applied to fluidised bed systems to gain a better understanding of the hydrodynamic behaviour involved. In the past, numerical models have considered only single particle sizes due to the added complexity of interaction between particles of differing sizes and densities. Industrial fluidised beds typically contain more than one particle size and density, therefore there is a need to develop a numerical model which takes this into account. The aim of this thesis is to develop and validate CFD techniques for modelling the behaviour of a gas-solid fluidised bed containing more than one particle size and density. To provide validation data for the numerical model, physical experiments are undertaken on a small two-dimensional bubbling gas-solid fluidised bed. Mixing and segregation behaviour of different materials are investigated. The experiments demonstrate that whilst only a small proportion of the bed consists of different size/density particles, significant changes in bed behaviour are apparent. Changes in bubble rise velocity, bubble size and bubble shape are observed. A number of constitutive equations must be included in the numerical model, including relationships for the momentum transfer between various phases and solids pressure. Different combinations of these constitutive equations are investigated. A new equation for particle-particle interactions is derived and included in a CFD model. The CFD model is validated against both data in the literature and physical experiments. From the validation studies, an optimum equation set is identified. This optimum equation set produces numerical results that closely resemble experimental bed behaviour, thus bringing the goal of solving scale-up problems one step closer. The use of this type of CFD model will ultimately result in timely and cost effective solutions for both the power generation and chemical processing industries.

While fluidized beds are commonly used in the pharmaceutical industry, the understanding of the fluidization processes is limited because no efficient tool is available for real-time online monitoring and measurement. In recent years, electrical capacitance tomography (ECT) has been used to investigate granulation, drying and coating processes in pharmaceutical fluidized beds. For measuring drying and granulation processes, a novel online calibration method was proposed and implemented to deal with continuous change in the moisture content of solids. Experiments were carried out using various fluidized beds of different scale, and good results were obtained. For monitoring the coating process in a Wurster fluidized bed, a unique ECT sensor is designed with three sets of electrodes. By this electrode combination, all regions of the Wurster fluidized bed can be monitored. Based on the work done so far, it is concluded that ECT is a very useful tool for monitoring and measurement of pharmaceutical fluidized beds.

Deep learning for continuous manufacturing of pharmaceutical solid dosage form

Diverse effects of climate at different times on grassland phenology in mid-latitude of the Northern Hemisphere

Chapter 7 - Advanced multiphase hybrid model development of fluidized bed wet granulation processes

A novel dual-material probe for in situ measurement of particle charge densities in gas–solid fluidized beds

This article also discusses the demonstration of a fluidized bed dryer, its principles, application, and other processing. This has led to the development of technology, processes, and equipment that not only reduce time but also increase output. A fluidized bed dryer significantly reduces drying time compared with a vacuum dryer or tray dryer. In the pharmaceutical industry, fluidized bed dryers are typically used for pellet drying, coating, andgranulation. Fluidized bed drying is very well known to yield high heat and mass transfer and is hence adopted in many industrial drying processes, particularly pharmacy products. In this paper, we show the construction and working of the fluidized bed dryer. It works on the drying principle. It has several advantages and disadvantages.

Manufacture and characterization of carbonated lightweight aggregates from waste paper fly ash

The pharmaceutical industry is facing significant economic challenges due to measures aimed at containing healthcare costs and evolving healthcare regulations. In this context, pharmaceutical laboratories seek to extend the lifespan of their machinery, particularly fluid bed dryers, which play a crucial role in the drug production process. Older fluid bed dryers, lacking advanced sensors for real-time temperature optimization, rely on fixed-time deterministic approaches controlled by operators. To address these limitations, a groundbreaking approach taking into account Exploration Data Analysis (EDA) and a Catboost machine-learning model is presented. This research aims to analyze and enhance a drug production process on a large scale, showcasing how AI algorithms can revolutionize the manufacturing industry. The Catboost model effectively reduces preheating phase time, resulting in significant energy savings. By continuously monitoring critical parameters, a paradigm shift from the conventional fixed-time models is achieved. It has been shown that the model is able to predict on average a reduction of 50.45% of the preheating process duration and up to 59.68% in some cases. Likewise, the energy consumption of the fluid bed dryer for the preheating process could be reduced on average by 50.48% and up to 59.76%, which would result on average in around 3.120 kWh energy consumption savings per year.

Natural extracts have potential in the pharmaceutical industry, cosmetics, and clinical applications because they are safe, non-toxic, and have relatively low side effects. Unfavorable taste and odor and stability problems are their disadvantages. The solution to these problems is microencapsulation technology. Microencapsulation is a technology that involves covering or coating a core substance with a polymer wall layer, resulting in micro-sized particles. The benefits of microencapsulation can protect compounds from various environmental factors such as oxidation, degradation, temperature, humidity, and light, thereby extending the shelf life of the product, improving the stability of active ingredients, preventing loss of activity, masking aromatic flavors and odors, improving the stability of volatile compounds and increasing bioavailability. The purpose of this review is to gather information about the application of microencapsulation to natural extracts and what the results of microencapsulation are. The literature review was conducted through Google Scholar and PubMed databases, and the literature selection was done using the PRISMA Flow Chart. This review results in microencapsulation technology for natural extracts made by ionic gelation, spray wet microencapsulation (SWM), solvent evaporation, freeze drying, fluid bed, and spray drying. Each method has a unique way of protecting the core substance with a polymer layer, resulting in useful microcapsules such as to reduce moisture, obtain suitable physicochemical characteristics, good flow rate, retain bioactive compounds, lower hygroscopicity, improve stability, increase shelf life, increase solubility, taste masking, maintain antioxidant content and pharmacological activity of natural ingredient extracts. This means the use of microencapsulation technology promises to improve the utilization of natural extracts in various pharmaceutical industries, cosmetics, and clinical applications. Keywords: Microencapsulation, Natural extracts, Methods, Applications ABSTRAK Ekstrak bahan alam memiliki potensi dalam industri farmasi, kosmetik dan aplikasi klinis karena aman, tidak beracun dan efek samping relative rendah. tetapi kelemahannya yaitu rasa dan bau yang tidak disukai serta masalah stabilitas. Solusi untuk masalah ini adalah teknologi mikroenkapsulasi. Mikroenkapsulasi adalah teknologi yang melibatkan penyalutan atau pelapisan zat inti oleh lapisan dinding polimer, menghasilkan partikel-partikel dengan ukuran mikro. Keunggulan mikroenkapsulasi dapat melindungi senyawa dari berbagai faktor lingkungan seperti oksidasi, degradasi, suhu, kelembaban, dan cahaya, sehingga dapat memperpanjang umur simpan produk, meningkatkan stabilitas bahan aktif, mencegah penurunan aktivitas, menutupi bau dan rasa, stabilitas dan bioavabilitas senyawa meningkat. Tujuan riview ini yaitu mengumpulkan informasi terkait aplikasi mikroenkapsulasi terhadap ekstrak bahan alam serta apa hasil dari mikroenkapsulasi tersebut. Kajian literatur dilakukan melalui database Google Scholar dan PubMed dengan seleksi literatur menggunakan Flow Diagram PRISMA. Hasil dari riview ini teknologi mikroenkapsulasi pada ekstrak bahan alam bisa dibuat dengan metode ionic gelation, spray wet microencapsulation (SWM), solvent evaporation, freeze drying, fluid bed, dan spray drying. Setiap metode memiliki cara unik dalam melindungi zat inti dengan lapisan polimer, sehingga menghasilkan mikrokapsul yang berguna seperti untuk mengurangi kelembaban, mendapatkan karakteristik fisikokimia yang sesuai, laju alir yang baik, mempertahankan senyawa bioaktif, menurunkan higroskopisitas, meningkatkan stabilitas, meningkatkan umur simpan, meningkatkan kelarutan, menutupi rasa, menjaga kandungan antioksidan dan aktivitas farmakologi ekstrak bahan alam. Penggunaan teknologi mikroenkapsulasi menjanjikan peningkatan dalam pemanfaatan ekstrak bahan alam dalam berbagai industri farmasi, kosmetik dan aplikasi klinis. Kata Kunci: Aplikasi, Ekstrak Bahan Alam, Metode, Mikroenkapsulasi.

Particle image velocimetry was used to investigate the evolution of multiple inlet gas jets located at the distributor base of a two‐dimensional fluidized bed setup. Results were used to estimate the solid circulation rate of the fluidized bed as well as particle‐entrainment into the individual jets. The effects of fluidization velocity, orifice diameter, orifice pitch, particle diameter, and particle density were studied. It was determined from this study that the solid circulation rate linearly increased with an increase in the fluidization velocity until the multiple jet system transitioned from isolated to an interacting system. In the interacting system of jets, the solid circulation increased with fluidization velocity but at a much lower rate. For multiple jet systems, this phenomenon may indicate the presence of an optimum operating condition with high circulation rate and low air input in the bed. © 2011 American Institute of Chemical Engineers AIChE J, 58: 3003–3015, 2012

Liquid–solid fluidized beds can meet many different demands from chemical, environmental, and pharmaceutical processes, and it is very crucial to accurately predict their voidages, which, however, are usually underestimated by the classical Richardson–Zaki equation. In this study, a data-driven modeling method was applied to develop the voidage correlation based on the experimental data from pilot-scale liquid–solid fluidized bed where the fluidization experiments of spherical glass beads were performed at different particle sizes, particle densities, liquid superficial velocities, and operating temperatures. By selecting different parametric spaces, various high-accuracy voidage correlations based on different dimensionless numbers (i.e., Re, Ret, Ar, Fr, St) were discovered and all of the values of R2 were approximately 0.99. In comparison, the combination of Re and Ar numbers could better characterize the voidage and the mean square error was as low as 2.29 × 10–4. The proposed correlation also performed very well in predicting the voidage of the fluidization of irregular calcite pellets in a pilot-scale fluidized bed and the voidage of the fluidization of coarse coal particles in a laboratory-scale fluidized bed, thus indicating its universality.