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Process intensification of pharmaceutical powder blending at commercial throughputs by utilizing semi-continuous mini-blending
| Contributor(s):: Maarten Jaspers, Florian Tegel, Timo P. Roelofs, Fabian Starsich, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff
Process intensification involves the miniaturization of equipment while retaining process throughput and performance. The pharmaceutical industry can benefit from this approach especially during drug product development, where the availability of active pharmaceutical ingredients (API) is often...
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Blend uniformity monitoring in a continuous manufacturing mixing process for a low-dosage formulation using a stream sampler and near infrared spectroscopy
| Contributor(s):: Rodolfo Romanach, Raúl S. Rangel-Gil, Juan M. Nasrala-Álvarez, Rafael Méndez
Continuous manufacturing has the potential to offer several benefits for the production of oral solid dosage forms, including reduced costs, low-scale equipment, and the application of process analytical technology (PAT) for real-time process control. This study focuses on the implementation of...
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A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction
| Contributor(s):: Hikaru G. Jolliffe, Martin Prostredny, Carlota Mendez Torrecillas, Ecaterina Bordos, Collette Tierney, Ebenezer Ojo, Richard Elkes, Gavin Reynolds, Yunfei Li Song, Bernhard Meir, Sara Fathollahi, John Robertson
Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body...
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CDER's Emerging Technology Program
| Contributor(s):: Thomas O’Connor
Emerging Technology Program (ETP) OverviewETP TrendsLifecycle of an Emerging TechnologyInteracting with the ETPPharmaceutical Quality Symposium 2023: Quality, Supply Chain & Advanced Manufacturing - 10/31/2023 | FDA
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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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Systematic development of a high dosage formulation to enable direct compression of a poorly flowing API: A case study
| Contributor(s):: Schaller, BE, Moroney, KM, Castro-Dominguez, B, Cronin, P, Belen-Girona, J, Ruane, P, Croker, DM, Walker, GM
In this work, the transfer of oral solid dosage forms, currently manufactured via wet granulation, to a continuous direct compression process was considered. Two main challenges were addressed: (1) a poorly flowing API (Canagliflozin) and (2) high drug loading (51 wt%). A scientific approach was...
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Mapping key process parameters to the performance of a continuous dry powder blender in a continuous direct compression system
| Contributor(s):: Palmer, J, Reynolds, GK, Tahir, F, Yadav, IK, Meehan, E, Holman, J, Bajwa, G
This work aims to expand the typical raw material attributes that can successfully be processed on a continuous direct compression line with a particular focus on the continuous dry powder blender. Three grades of Acetaminophen were investigated as model active pharmaceutical ingredients and...
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Impact of blend properties and process variables on the blending performance
| Contributor(s):: Bekaert, B, Grymonpre, W, Novikova, A, Vervaet, C, Vanhoorne, V
In this study, quantitative relationships were established between blend properties, process settings and blending responses via multivariate data-analysis. Four divergent binary blends were composed in three different ratios and processed at various throughputs and impeller speeds. Additionally,...
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Impact of blend properties on die filling during tableting
| Contributor(s):: Van Snick, B., Grymonpre, W., Dhondt, J., Pandelaere, K., Di Pretoro, G., Remon, J. P., De Beer, T., Vervaet, C., Vanhoorne, V.
Based on characterization of a wide range of fillers and APIs, thirty divergent blends were composed and subsequently compressed on a rotary tablet press, varying paddle speed and turret speed. The tablet weight variability was determined of 20 grab samples consisting of each 20 tablets....
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Effects of process parameters on tablet critical quality attributes in continuous direct compression: a case study of integrating data-driven statistical models and mechanistic compaction models
| Contributor(s):: Huang, Zhuangrong, Galbraith, Shaun C., Cha, Bumjoon, Liu, Huolong, Park, Seoyoung, Flamm, Matthew H., Metzger, Matt, Tantuccio, Anthony, Yoon, Seongkyu
Continuous manufacturing of oral-dosage drug products is increasing the need for rigorous process understanding both from a process design and control perspective. The purpose of this study is to develop a methodology that analyzes the effects of upstream process parameters on continuous tablet...
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Development and Use of a Residence Time Distribution (RTD) Model Control Strategy for a Continuous Manufacturing Drug Product Pharmaceutical Process
| Contributor(s):: Hurley, Samantha, Tantuccio, Anthony, Escotet-Espinoza, Manuel Sebastian, Flamm, Matthew, Metzger, Matthew
Residence-time-distribution (RTD)-based models are key to understanding the mixing dynamics of continuous manufacturing systems. Such models can allow for material traceability throughout the process and can provide the ability for removal of non-conforming material from the finished product....
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Development of a continuous direct compression platform for low-dose drug products
| Contributor(s):: Van Snick, B, Holman, J, Vanhoorne, V, Kumar, A, De Beer, T, Remon, JP, Vervaet, C
In this work a continuous direct compression process was developed for a low-dosed drug product. Each unit operation of the GEA CDC-50 system was thoroughly investigated. This paper aimed to tackle the macroscopic and microscopic blend uniformity challenges inherently associated with continuous...
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Determination of a quantitative relationship between material properties, process settings and screw feeding behavior via multivariate data-analysis
| Contributor(s):: Bekaert, B, Penne, L, Grymonpre, W, Van Snick, B, Dhondt, J, Boeckx, J, Vogeleer, J, De Beer, T, Vervaet, C, Vanhoorne, V
In this study, a quantitative relationship between material properties, process settings and screw feeding responses of a high-throughput feeder was established via multivariate models (PLS). Thirteen divergent powders were selected and characterized for 44 material property descriptors. During...
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Continuous direct compression as manufacturing platform for sustained release tablets
| Contributor(s):: Vanhoorne, V, Holman, J., Cunningham, C., Kumar, A., Vercruysse, J., De Beer, T., Remon, J. P, Vervaet, C
This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard...
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Continuous direct compression: Development of an empirical predictive model and challenges regarding PAT implementation
| Contributor(s):: Bekaert, B., Van Snick, B., Pandelaere, K., Dhondt, J., Di Pretoro, G., De Beer, T., Vervaet, C., Vanhoorne, V.
In this study, an empirical predictive model was developed based on the quantitative relationships between blend properties, critical quality attributes (CQA) and critical process parameters (CPP) related to blending and tableting. The blend uniformity and API concentration in the tablets were...
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A very boring 120 h: 15million tablets under a continuous state of control
| Contributor(s):: Holman, James, Tantuccio, Anthony, Palmera, Jhon, Doninck, Tom van, Meyer, Robert
The aimof this study is to showthe robustness of a commercial direct compression system running continuously under relevant process conditions for over 120 h. The study will apply a representative commercial control strategy including real time monitoring of process parameters, rejection of OOS...
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A multivariate raw material property database to facilitate drug product development and enable in-silico design of pharmaceutical dry powder processes
| Contributor(s):: Van;Snick, B, Dhondt, JPandelaere, K, Bertels, J, Mertens, R, Klingeleers, D, Di, Pretoro, G, Remon, JP, Vervaet, C, De, Beer, T, Vanhoorne, V
In current study a holistic material characterization approach was proposed and an extensive raw material property database was developed including a wide variety of APIs and excipients with different functionalities. In total 55 different materials were characterized and described by over 100...