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Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation
Contributor(s):: Kumar, Ashish, Alakarjula, Maija, Vanhoorne, Valerie, Toiviainen, Maunu, De Leersnyder, Fien, Vercruysse, Jurgen, Juuti, Mikko, Ketolainen, Jarkko, Vervaet, Chris, Remon, Jean Paul, Gernaey, Krist V., De Beer, Thomas, Nopens, Ingmar
Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and...
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Loss-in-Weight Feeding Trials Case Study: Pharmaceutical Formulation
Contributor(s):: Engisch, WE, Muzzio, FJ
This article presents a case study of a continuous feeding strategy for five pharmaceutical components (active pharmaceutical ingredient (API), Prosolv HD90, crospovidone, magnesium stearate, and colloidal silicon dioxide), for the purpose of developing a direct compression continuous...
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Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing
Contributor(s):: Allenspach, Carl, Timmins, Peter, Lumay, Geoffroy, Holman, James, Minko, Tamara
Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both...
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Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets
Contributor(s):: Taipale-Kovalainen, Krista, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Korhonen, Ossi
The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental...
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Lubrication empirical model to predict tensile strength of directly compressed powder blends
Contributor(s):: Nassar, Joelle, Williams, Ben, Davies, Conrad, Lief, Kevin, Elkes, Richard
A new approach is proposed to support prediction of tablet tensile strength as a function of both solid fraction (and/or compression pressure) and extent of lubrication by using empirical data to parameterise the model. This is a pre-requisite for simulation of the compaction unit operation where...
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Introduction to the Theory and Practice of Sampling
Contributor(s):: Esbensen, Kim H
Sampling is an important, but sometimes hidden, part of everyday life in science, technology, industry, society and commerce where decisions are made based on analytical results, which must be based on reliable samples. However, there is a very long and complex pathway from heterogeneous...
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Investigating the Effect of APAP Crystals on Tablet Behavior Manufactured by Direct Compression
Contributor(s):: Ghazi, Nastaran, Liu, Zhanjie, Bhatt, Chinmay, Kiang, San, Cuitino, Alberto
In this work, the effect of API's (Active Pharmaceutical Ingredient) shape and size on tablet characteristics is investigated for high API dose formulation manufactured by direct compression. Three different classes of APAP (acetaminophen) are selected, and tablets are produced in both single and...
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Investigation of Preprocessing and Validation Methodologies for PAT: Case study of the granulation and coating steps for the manufacturing of ethenzamide tablets
Contributor(s):: Shibayama, Shojiro, Funatsu, Kimito
After the Food and Drug Association in the USA published guidelines on the enhanced use of process analytical technology (PAT) and continuous manufacturing, many studies regarding PAT and continuous manufacturing have been published. This paper describes a case study involving granulation and...
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Investigation of the effect of impeller rotation rate, powder flow rate, and cohesion on powder flow behavior in a continuous blender using PEPT
Contributor(s):: Portillo, PM, Vanarase, AU, Ingram, A, Seville, JK, Ierapetritou, MG, Muzzio, FJ
In this paper, we examine the movement of particles within a continuous powder mixer using PEPT (Positron Emission Particle Tracking). The benefit of the approach is that the particle movement along the vessel can be measured non-invasively. The effect of impeller rotation rate, powder flow rate,...
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Investigation of the variability of NIR in-line monitoring of roller compaction process by using Fast Fourier Transform (FFT) analysis
Contributor(s):: Feng, Tao, Wang, Feng, Pinal, Rodolfo, Wassgren, Carl, Carvajal, M. Teresa
The purpose of this Research Article was to investigate the variability of the roller compaction process while monitoring in-line with near-infrared (NIR) spectroscopy. In this paper, a pragmatic method in determining this variability of in-line NIR monitoring roller compaction process was...
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Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line
Contributor(s):: Fulop, G., Domokos, A., Galata, D., Szabo, E., Gyurkes, M., Szabo, B., Farkas, A., Madarasz, L., Demuth, B., Lender, T., Nagy, T., Kovacs-Kiss, D., Van der Gucht, f, Marosi, G., Nagy, Z. K.
Highly homogeneous low-dose (50 mu g) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a...
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Integrating sensors for monitoring blend content in a pharmaceutical continuous manufacturing plant
Contributor(s):: Panikar, Savitha, Li, Jingzhe, Rane, Varsha, Gillam, Sean, Callegari, Gerardo, Kurtyka, Bogdan, Lee, Sau, Muzzio, Fernando
In a pharmaceutical manufacturing process, Critical Quality Attributes (CQAs) need to be monitored not only for the final product but also for intermediates. Blend uniformity of powders is one such attribute that needs to be measured to ensure the quality of the final product. Multiple in-line...
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Intelligent Alarm Management Applied to Continuous Pharmaceutical Tablet Manufacturing: An Integrated Approach
Contributor(s):: Gupta, Anshu, Giridhar, Arun, Venkatasubramanian, Venkat., Reklaitis, Gintaras V.
One important aspect of effective real time process management is the implementation of intelligent systems that can assist human operators in making supervisory control decisions. Conventional practice is to simply sound alarms when process variables go out of range leaving it to the operator to...
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In-line monitoring and optimization of powder flow in a simulated continuous process using transmission near infrared spectroscopy
Contributor(s):: Alam, Md Anik, Shi, Zhenqi, Drennen, James K, Anderson, Carl A
In-line monitoring of continuous powder flow is an integral part of the continuous manufacturing process of solid oral dosage forms in the pharmaceutical industry. Specifically, monitoring downstream from loss-in-weight (LIW) feeders and/or continuous mixers provides important data about the...
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In-line monitoring of granule moisture in fluidized-bed dryers using microwave resonance technology
Contributor(s):: Buschmueller, Caroline, Wiedey, Wolfgang, Doescher, Claas, Dressler, Jochen, Breitkreutz, Joerg
This is the first report on in-line moisture measurement of pharmaceutical products by microwave resonance technology. In order to meet the FDA's PAT approach, a microwave resonance sensor appropriate for pharmaceutical use was developed and implemented into two different fluidized-bed dryers....
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In-line monitoring of low drug concentration of flowing powders in a new sampler device
Contributor(s):: Sierra-Vega, Nobel O, Méndez, Rafael, Martínez-Cartagena, Pedro; Alvarado-Hernández, Bárbara B; Romañach, Rodolfo J.
A novel sampler device for flowing powders was tested to quantify drug concentrations as low as 0.76% w/w in pharmaceutical powder blends. The sampler device was developed based on the powder flow behavior within a tablet press feed frame, following the principles laid down in the Theory of...
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In-line monitoring of the drug content of powder mixtures and tablets by near-infrared spectroscopy during the continuous direct compression tableting process
Contributor(s):: Järvinen, Kristiina, Hoehe, Wolfgang, Järvinen, Maiju, Poutiainen, Sami, Juuti, Mikko, Borchert, Sven
Continuous manufacturing methods offer economic and quality advantages when compared with batch manufacturing methods. In continuous manufacturing, one requires real time assurance of quality of product via the implementation of PAT tools. This study focuses on an in-line near-infrared (NIR)...
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In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid process understanding and development
Contributor(s):: Madarász, Lajos, Köte, Ákos, Hambalkó, Bence, Csorba, Kristóf, Kovács, Viktor, Lengyel, László, Marosi, Györgya, Farkas, Attilaa, Nagy, Zsombor Kristóf, Domokos, András
The present paper serves as a demonstration how an in-line PAT tool can be used for rapid and efficient process development in a fully continuous powder to granule line consisting of an interconnected twin-screw wet granulator, vibrational fluid bed dryer, and a regranulating mill. A new method...
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In-Line Quantification of Drug and Excipients in Cohesive Powder Blends by near Infrared Spectroscopy
Contributor(s):: Liew, C. V., Karande, A. D., Heng, P. W. S
This work was aimed at investigating the utility of near infrared (NIR) spectroscopy for simultaneous in-line quantification of drug and excipients in cohesive powder blends in a bin blender. A model formulation containing micronized chlorpheniramine maleate (μCPM), lactose, microcrystalline...
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In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process
Contributor(s):: Nagy, Brigitta, Farkas, Attila, Gyurkes, Martin, Komaromy-Hiller, Szofia, Demuth, Balazs, Szabo, Bence, Nusser, David, Borbas, Eniko, Marosi, Gyorgy, Nagy, Zsombor Kristof
The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a...
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In-line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)
Contributor(s):: Schlindwein, Walkiria, Bezerra, Mariana, Almeida, Juan, Berghaus, Andreas, Owen, Martin, Muirhead, Gordon
This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line...
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Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion
Contributor(s):: Wesholowski, Jens, Prill, Sebastian, Berghaus, Andreas, Thommes, Markus
Hot-melt extrusion on co-rotating twin screw extruders is a focused technology for the production of pharmaceuticals in the context of Quality by Design. Since it is a continuous process, the potential for minimizing product quality fluctuation is enhanced. A typical application of hot-melt...
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Influence of binder attributes on binder effectiveness in a continuous twin screw wet granulation process via wet and dry binder addition
Contributor(s):: Vandevivere, L., Denduyver, P., Portier, C., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.
The effect of a wide variety of binders on the quality of granules produced via continuous twin screw wet granulation was studied. Anhydrous dicalcium phosphate was used as poorly soluble filler and was granulated applying dry or wet addition of binders. Furthermore, dry and wet binder...
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Influence of filler selection on twin screw foam granulation
Contributor(s):: Rocca, K. E., Weatherley, S., Sheskey, P. J., Thompson, M. R.
The influence of filler selection in wet granulation was studied for the novel case where the binder is delivered as an unstable, semi-rigid aqueous foam to an extrusion process. The work primarily examined the impact of differing concentrations of microcrystalline cellulose (Avicel PH (R) 101)...
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Influence of granulation temperature on particle size distribution of granules in twin-screw granulation (TSG)
Contributor(s):: Ito, Akihiko, Kleinebudde, Peter
This study investigated an influence of granulation temperature during twin-screw granulation (TSG) on particle size distributions (PSDs). The influence of the granulation temperature on granule size distributions varied, depending on the liquid to solid (L/S) ratio, the kind of binders, the...