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Challenges, opportunities and recent advances in near infrared spectroscopy applications for monitoring blend uniformity in the continuous manufacturing of solid oral dosage forms
Contributor(s):: Velez, Natasha L., Drennen, James K., Anderson, Carl A.
Near infrared (NIR) spectroscopy has been widely recognized as a powerful PAT tool for monitoring blend uniformity in continuous manufacturing (CM) processes. However, the dynamic nature of the powder stream and the fast rate at which it moves, compared to batch processes, introduces challenges...
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Characterization of material properties
Contributor(s):: Razavi, Sonia, Oka, Sarang, Escotet-Espinoza, M. Sebastian, Wang, Yifan, Li, Tianyi, Futran Mauricio., Muzzio, Fernando
This chapter describes the importance of deepening our understanding of material properties and their effect on process performance. There are many measurement techniques to describe the complex nature of powders, some of which are provided in this chapter. Strong knowledge of multivariate...
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Characterization of Near-Infrared and Raman Spectroscopy for In-Line Monitoring of a Low-Drug Load Formulation in a Continuous Manufacturing Process
Contributor(s):: Harms, Zachary, Shi, Zhenqi: Kulkarni, Rajesh, Myers, David P.
Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order...
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Characterization of NIR interfaces for the feeding and in-line monitoring of a continuous granulation process
Contributor(s):: Román-Ospino, Andrés D, Tamrakar, Ashutosh Igne, Benoît Dimaso, Elyse Towns Airiau, Christian Clancy, Donald J Pereira, Glinka Muzzio, Fernando J Singh, Ravendra, Ramachandran, Rohit
This work describes the characterization of three NIR interfaces intended to monitor a continuous granulation process. Two interfaces (i.e. a barrel interface and a rotating paddle interface) were evaluated to monitor the API concentration at the entrance of the granulator, and a third interface...
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Automated and continuous synthesis of drug substances
Contributor(s):: Sacher, Stephan, Castillo, Ismael, Rehrla, Jakob, Sagmeistera, Peter, Lebl, René, Kruisza, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D, Kirschneck, Dirk, Kappea, C. Oliver, Horn, Martin
A continuous synthesis line was developed integrating different common reaction stepsnamely nitration, substitution and hydrogenation. Mesalazine as model drug substancewas produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PATstrategy was implemented to equip the full...
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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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Breaking Through Barriers to Continuous Manufacturing
Contributor(s):: Markarian, Jennifer
Pharmaceutical manufacturing is inching towards implementing more efficient and sustainable processes, including continuous manufacturing (CM) of solid-dosage drugs. Advantages of CM include the potential for faster development, easier technical transfer, and more efficient and flexible...
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Assessment and prediction of tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy
Contributor(s):: Peeters, Elisabeth, Tavares da Silva, Ana Filipa, Toiviainen, Maunu, Van Renterghem, Jeroen, Vercruysse, Jurgen, Juuti, Mikko, Lopes, Joao Almeida, De Beer, Thomas., Vervaet, Chris, Remon, Jean-Paul
This study investigated whether Raman and Near Infrared (NIR) spectroscopy could predict tablet properties. Granules were produced on a continuous line by varying granulation parameters. Tableting process parameters were adjusted to obtain uniform tablet weight and thickness. Spectra were...
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Assessment of blend uniformity in a continuous tablet manufacturing process
Contributor(s):: Sierra-Vega, Nobel, Román-Ospino, Andrés, Scicolone, James, Muzzio, Fernando, Romañach, Rodolfo, Mendez, Rafael
Blend uniformity was monitored throughout a continuous manufacturing (CM) process by near infrared (NIR) spectroscopic measurements of flowing blends and compared to the drug concentration in the tablets. The NIR spectra were obtained through the chute after the blender and within the feed frame,...
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Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review
Contributor(s):: Simon, Levente L, Pataki, Hajnalka, Marosi, György, Meemken, Fabian, Hungerbühler, Konrad, Baiker, Alfons, Tummala, Srinivas, Glennon, Brian, Kuentz, Martin, Steele, Gerry, Kramer, Herman J. M, Rydzak, James W.
This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in...
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Assessment of Robustness for a Near-Infrared Concentration Model for Real-Time Release Testing in a Continuous Manufacturing Process
Contributor(s):: Colon, Yleana, Vargas, Jenny, Sánchez, Eric, Navarro, Gilfredo, Romañach, Rodolfo
This study describes the robustness test of a transmission near-infrared spectroscopic (NIRS) model for prediction of drug concentration in core tablets as part of real-time release testing (RTRt) efforts for a continuous manufacturing process. Seven calibration blend samples were prepared...
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Application of Near-Infrared Spectroscopy in Real-Time Monitoring of Product Attributes of Ribbed Roller Compacted Flakes
Contributor(s):: Samanta, Asim Kumar, Karande, Atul D., Ng, Ka Yun, Heng, Paul Wan Sia
This study assessed the utility of near-infrared (NIR) spectroscopy for the real-time monitoring of content uniformity and critical quality attributes (tensile strength, Young's modulus, and relative density) of ribbed roller compacted flakes made by axially corrugated or ribbed rolls. A...
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Application of the quantitative detection of a change in concentration of magnesium stearate in a feeder tube of tableting manufacture by real-time near-infrared spectroscopy
Contributor(s):: Sasakura, D., Nakayama, K., Chikuma, T.
Process analytical technology is important for the analysis and control of manufacturing processes. Near-infrared spectroscopy is widely used in various process analytical technologies for the analysis of the chemical components of solid dosage forms. Lubrication is an important process carried...
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Application of X-Ray Sensors for In-line and Noninvasive Monitoring of Mass Flow Rate in Continuous Tablet Manufacturing
Contributor(s):: Ganesh, Sudarshan, Troscinski, Rachel, Schmall, Nicholas, Nagy, Zoltan, Reklaitis, Gintaras
The progress in continuous downstream manufacturing of oral solid doses demands effective real-time process management, with monitoring at its core. This study evaluates the feasibility of using a commercial sensor to measure the mass flow rate of the particulates, a critical process variable in...
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Approach to establishment of control strategy for oral solid dosage forms using continuous manufacturing
Contributor(s):: Ishimoto, Hayato, Kano, Manabu, Sugiyama, Hirokazu, Takeuchi, Hirofumi, Terada, Katsuhide, Aoyama, Atsushi, Shoda, Takuji, Demizu, Yosuke, Shimamura, Jinen, Yokoyama, Reiji, Miyamoto, Yuji, Hasegawa, Koji, Serizawa, Masaru, Unosawa, Kazuomi, Osaki, Kazuo, Asai, Naochika, Matsuda, Yoshihiro
As a result of the Research Article activities of the Japan Agency for Medical Research Article and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology...
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Evaluation of three approaches for real-time monitoring of roller compaction with near-infrared spectroscopy
Contributor(s):: Acevedo, D., Muliadi, A., Giridhar, A., Litster, J. D., Romañach, R. J.
Three different approaches have been evaluated for monitoring ribbon density through real-time near-infrared spectroscopy measurements. The roll compactor was operated to produce microcrystalline cellulose (MCC) ribbons of varying densities. The first approach used the slope of the spectra which...
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Application of Continuous Crystallization in an Integrated Continuous Pharmaceutical Pilot Plant
Contributor(s):: Zhang, Haitao, Lakerveld, Richard, Heider, Patrick, Tao, Mengying, Su, Min, Testa, Christopher, D’Antonio, Alyssa, Barton, Paul, Braatz, Richard, Trout, Bernhardt, Myerson, Allan, Jensen, Klavs, Evans, James
Real-time control using process analytical technology (PAT) tools is required for the implementation of continuous crystallization within integrated continuous manufacturing (ICM) of pharmaceuticals. However, appropriate selection of PAT tools is challenging, and the design and operation of...
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Application of FT-NIR Analysis for In-line and Real-Time Monitoring of Pharmaceutical Hot Melt Extrusion: a Technical Note
Contributor(s):: Vo, Anh Q., He, Herman, Zhang, Jiaxiang, Martin, Scott, Chen, Rui, Repka, Michael A.
Continuous manufacturing, a gaining interest paradigm in the pharmaceutical industry, requires in-process monitoring of critical process parameters to ensure product consistency. This study demonstrated the application of Fourier transform near-infrared (FT-NIR) spectroscopy in conjunction with...
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An Innovative Sampling Interface for Monitoring Flowing Pharmaceutical Powder Mixtures
Contributor(s):: Martínez-Cartagena, Pedro, Romañach, Rodolfo J., Sierra-Vega, Nobel O; Alvarado-Hernández, Bárbara B; Méndez, Rafael
A chute was designed following the principles of the Theory of Sampling to minimize the variations in powder flow and provide all particles in the flowing blends with the same opportunity of being selected as a sample. The design also reduces the thickness of the chute to allow the analysis of a...
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An ontological knowledge-based system for the selection of process monitoring and analysis tools
Contributor(s):: Singh, Ravendra, Gernaey, Krist V, Gani, Rafiqul
Efficient process monitoring and analysis tools provide the means for automated supervision and control of manufacturing plants and therefore play an important role in plant safety, process control and assurance of end product quality. The availability of a large number of different process...
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Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy
Contributor(s):: Mateo-Ortiz Daniel, Colon, Yleana, Romañach, Rodolfo, Mendez, Rafael
New analytical methods are needed to understand and optimize the processes by which tablets are produced. Fette 3090 tablet presses are commonly used in the pharmaceutical industry. A near-infrared (NIR) probe was installed into a Fette 3090 feed frame to understand and monitor the die filling...
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Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation
Contributor(s):: Matsunami, Kensaku, Ryckaert, Alexander, Peeters, Michiel, Badr, Sara, Sugiyama, Hirokazu, Nopens, Ingmar, De Beer, Thomas
Toward further implementation of continuous tablet manufacturing, one key issue is the time needed for start-up operation because it could lead to lower product yield and reduced economic performance. The behavior of the start-up operation is not well understood; moreover, the definition of the...
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Analytical Method Quality by Design for an On-Line Near-Infrared Method to Monitor Blend Potency and Uniformity
Contributor(s):: Corredor, Claudia, Bu, Xin, McCann, Ryan, Dougherty, Jeffrey, Stevens, Tim, Both, Douglas, Shah, Pankaj
In this work, an example of analytical method quality by design (AQbD) principles applied to an in-line NIR method to monitor blend potency and uniformity in the manufacturing of an oral solid dosage product is presented. An integrated process analytical technology (PAT) method was developed...
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Advanced Pharmaceutical Manufacturing: A Functional Definition
Contributor(s):: Romañach, Rodolfo J., Stelzer, Torsten, Sanchez, Eric, Muzzio, Fernando
The term “Advanced Pharmaceutical Manufacturing” (APM) has become an ubiquitous buzzword with deep potential policy implications. There is a real danger that APM will be seen as a general panacea for solving economic woes and drug shortages, devoiding it from specific meaning, and depriving the...
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Advanced Real-Time Process Analytics for Multistep Synthesis in Continuous Flow
Contributor(s):: Sagmeister, Peter, Lebl, René, Castillo, Ismael, Rehrl, Jakob, Kruisz, Julia, Sipek, Martin, Horn, Martin, Sacher, Stephan, Cantillo, David, Williams, Jason D, Kappe, Oliver
In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and...