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Lubricant Sensitivity of Direct Compression Grades of Lactose in Continuous and Batch Tableting Process
| Contributor(s):: Gerald A. Hebbink, Pauline H. M. Janssen, Jurjen H. Kok, Lorenzo Menarini, Federica Giatti, Caterina Funaro, Salvatore Fabrizio Consoli, Bastiaan H. J. Dickhoff
Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as they increase efficiency and improve quality control. Compared to batch blending, continuous blending is easier to scale and...
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Case study: Commercializing a continuous direct compression product with a novel control strategy
| Contributor(s):: Frank Witulski
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Process intensification using a semi-continuous mini-blender to support continuous direct compression processing
| Contributor(s):: Alexandra Lohrmann, Florian Tegel, Muhammad Khalid Maqsood, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff, Maarten Jaspers, Timo P. Roelofs
The production of pharmaceutical tablets is shifting towards continuous manufacturing. Therefore, individual unit operations such as powder blending need to be re-designed. Continuous powder blending has been implemented successfully, but for low-dose formulations this is challenging due to...
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Tracking raw material flow through a continuous direct compression line. Part II of II: Predicting dynamic changes in quality attributes of tablets due to disturbances in raw material properties using an independent residence time distribution model
| Contributor(s):: Peterwitz, M, Buchgeister, SMeier, R, Schembecker, G
Continuous manufacturing of pharmaceuticals promises many advantages regarding economics and quality. However, tracing deviating material in such processes is much more challenging than in batch processes due to axial back-mixing. The literature has proven the traceability of disturbances in the...
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Starch Products as Candidate Excipients in a Continuous Direct Compression Line
| Contributor(s):: Sonia M. Razavi, Yi Tao, James Scicolone, Tami Morker, Charles Cunningham, Ali Rajabi-Siahboomi, Douglas B. Hausner, Fernando J. Muzzio
Purpose Direct compression (DC) remains the most preferred technique to produce tablets, and its effectiveness is directly influenced by raw material attributes. Therefore, the selection of specific grades of excipients to achieve desirable powder flow and compression properties is of importance....
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Robustness of a continuous direct compression line against disturbances in feeding
| Contributor(s):: Karttunen A.-P., Poms J., Sacher S., Sparén A., Ruiz Samblás C., Fransson M., Martin De Juan L., Remmelgas J., Wikström H., Hsiao W.-K., Folestad S., Korhonen O.
The aim of the current study was to characterize the robustness of an integrated continuous direct compression (CDC) line against disturbances from feeding, i.e. impulses of API and short step disturbances. These disturbances mimicked typical variations that can be encountered during long-term...
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Recent progress in continuous manufacturing of oral solid dosage forms
| Contributor(s):: Vanhoorne, Valérie, Vervaet, Chris
Continuous drug product manufacturing is slowly being implemented in the pharmaceutical industry. Although the benefits related to the quality and cost of continuous manufacturing are widely recognized, several challenges hampered the widespread introduction of continuous manufacturing of drug...
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Provoking an end-to-end continuous direct compression line with raw materials prone to segregation
| Contributor(s):: Lakio, Satu, Ervasti, Tuomas, Tajarobi, Pirjo, Wikstrom, Hakan, Fransson, Magnus, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Folestad, Staffan, Abrahmsen-Alami, Susanna, Korhonen, Ossi
Continuous manufacturing of solid oral dosage forms is promising for increasing the efficiency and quality of pharmaceutical production and products. In this study a whole train continuous direct compression (CDC) line has been provoked using challenging formulations typically prone to...
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Quality Risk Assessment and Mitigation of Pharmaceutical Continuous Manufacturing Using Flowsheet Modeling Approach
| Contributor(s):: Tian, Geng;, Koolivand, Abdollah, Arden, Nilou S., Lee, Sau, O'Connor, Thomas F.
Integrated flowsheet modeling is an engineering approach that can provide a framework for understanding the impact of process dynamics on drug quality and associated risks during production, thereby facilitating the development of robust continuous processes. In this investigation, flowsheet...
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Process Analytical Technology for continuous manufacturing of solid-dosage forms
| Contributor(s):: Fonteyne, Margot;, Vercrusysse, Jurgen, De Leersnyder, Fien, Van Snick, Bernd, Vervaet, Chris, Remon, Jean, De Beer, Thomas
Currently, pharmaceutical production is making the switch from batch processing towards continuous processing. The quality of intermediate and end products produced by batch processes is assured by off-line testing. It is obvious that off-line tests in analytical laboratories cancel out the...
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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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Impact of Vertical Blender Unit Parameters on Subsequent Process Parameters and Tablet Properties in a Continuous Direct Compression Line
| Contributor(s):: Kreiser, MJ, Wabel, C, Wagner, KG
The continuous manufacturing of solid oral-dosage forms represents an emerging technology among the pharmaceutical industry, where several process steps are combined in one production line. As all mixture components, including the lubricant (magnesium stearate), are passing simultaneously through...
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Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes
| Contributor(s):: Chen, Liang, He, Zizhou, Kunnath, Kuriakose, Zheng, Kai, Kim, Sangah, Dave, Rajesh N.
Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid...
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Crystal and Particle Engineering Strategies for Improving Powder Compression and Flow Properties to Enable Continuous Tablet Manufacturing by Direct Compression
| Contributor(s):: Chattoraj, Sayantan, Sun, Changquan Calvin
Continuous manufacturing of tablets has many advantages, including batch size flexibility, demand-adaptive scale up or scale down, consistent product quality, small operational foot print, and increased manufacturing efficiency. Simplicity makes direct compression the most suitable process for...
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Continuous manufacturing of delta mannitol by cospray drying with PVP
| Contributor(s):: Vanhoorne, V., Van Bockstal, P-J., Van Snick, B., Peeters, E., Monteyne, T., Gomes, P., De Beer, T., Remon, J. P., Vervaet, C.
Mannitol is a frequently used diluent in the production of tablets due to its non-hygroscopic character and low drug interaction potential. Although the delta-polymorph of mannitol has superior tabletability in comparison to alpha- and beta-mannitol, the latter are most commonly used because...
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Comparison between integrated continuous direct compression line and batch processing - The effect of raw material properties
| Contributor(s):: Karttunen, AP, Wikstrom, HTajarobi, P, Fransson, M, Sparen, A, Marucci, M, Ketolainen, J, Folestad, S, Korhonen, O, Abrahmsen-Alami, S
There is a current trend in pharmaceutical manufacturing to shift from traditional batch manufacture to continuous manufacturing. The purpose of this study was to test the ability of an integrated continuous direct compression (CDC) line, in relation to batch processing, to achieve consistent...
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Characterization of a novel hydroxypropyl methylcellulose (HPMC) direct compression grade excipient for pharmaceutical tablets
| Contributor(s):: Allenspach, Carl, Timmins, Peter, Sharif, Shasad, Minko, Tamara
Controlled release tablets are important dosage forms enabling a slower release of the drug and better pharmacokinetics for some drugs and hydrophilic matrix tablets utilizing hydroxypropyl methylcellulose (HPMC) are one of the most common types. One of the main challenges with using HPMC is its...
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Benchtop NIR method development for continuous manufacturing scale to enable efficient PAT application for solid oral dosage form
| Contributor(s):: Alam, MA, Liu, YADolph, S, Pawliczek, M, Peeters, E, Palm, A
A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to...
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An agile and robust in-line NIR potency deviation detection method for monitoring and control of a continuous direct compression process
| Contributor(s):: Alam, Md Anik, Liu, Yang Angela
Near Infrared (NIR) method for blend potency estimation has been commonly used as an essential tool for process monitoring and control in continuous manufacturing of solid oral dosage forms. Robustness has been the main challenge for successful application of an NIR method, which often results in...
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A Training on: Continuous Manufacturing (Direct Compaction) of Solid Dose Pharmaceutical Products
| Contributor(s):: Moghtadernejad, Sara, Escotet-Espinoza, M. Sebastian, Oka, Sarang, Singh, Ravendra, Liu, Zhanjie, Roman-Ospino, Andres D., Li, Tianyi, Razavi, Sonia, Panikar, Savitha, Scicolone, James, Callegari, Gerardo, Hausner, Douglas, Muzzio, Fernando
As the pharmaceutical industry increasingly adopts continuous manufacturing technology, significant attention must be paid to process analytical technology (PAT), process integration, and process control. Published information is no substitute for hands-on comprehensive training, which is...
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A Co-Processed API Approach for a Shear Sensitive Compound Affording Improved Chemical Stability and Streamlined Drug Product Processing
| Contributor(s):: Schenck, L, Neri, CJia, XJ, Schafer, W, Axnanda, S, Canfield, N, Li, F, Shah, V
The physical properties of active pharmaceutical ingredients (API) are critical to both drug substance (DS) isolation and drying operations, as well as streamlined drug product (DP) processing and the quality of final dosage units. High aspect ratio, low bulk density, API 'needles' in particular...