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A Co-Processed API Approach for a Shear Sensitive Compound Affording Improved Chemical Stability and Streamlined Drug Product Processing
09 Jun 2023 | 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...
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A Combined Feed-Forward/Feed-Back Control System for a QbD-Based Continuous Tablet Manufacturing Process
09 Jun 2023 | Contributor(s): Singh, Ravendra, Muzzio, Fernando J, Ierapetritou, Marianthi, Ramachandran, Rohit
Continuous pharmaceutical manufacturing together with PAT (Process Analytical Technology) provides a suitable platform for automatic control of the end product quality as desired by QbD (quality by design)-based efficient manufacturing. The precise control of the quality of the pharmaceutical...
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A Comparative Investment Analysis of Batch Versus Continuous Pharmaceutical Manufacturing Technologies
04 Oct 2023 | Peer-reviewed journal | Contributor(s): Clifford V. Rossi
Purpose This study examines the risks and economics associated with investing in continuous (CM) versus conventional batch manufacturing for production of oral solid dosage pharmaceutical (OSD) products in the USA and abroad. Methods A stochastic net present value (NPV) simulation of brand...
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A Comparison Between Lab-Scale and Hot-Melt-Extruder-Based Anti-inflammatory Ointment Manufacturing
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Thakkar, R, Ashour, EAShukla, A, Wang, R, Chambliss, WG, Bandari, S, Murthy, N, Repka, MA
Hot-melt extrusion (HME) has been extensively investigated for continuous manufacturing of amorphous solid dispersions, to improve the solubility of poorly water-soluble drug substances, impart abuse deterrence to controlled substances, taste masking for pediatric and geriatric formulations and...
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A comprehensive analysis and optimization of continuous twin-screw granulation processes via sequential experimentation strategy
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Meng, Wei, Rao, Kallakuri Suparna, Snee, Ronald D., Ramachandran, Rohit., Muzzio, Fernando J
Nowadays twin-screw granulation has been emerging as an attractive continuous wet granulation technique. This study was geared towards better process design and understanding with emphasis on bridging the knowledge gap between input and output variables by employing sequential experimentation...
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A continuous manufacturing concept for a pharmaceutical oral suspension
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bostijn, N, Van, Renterghem, JDhondt, W, Vervaet, C, De;Beer, T
The aim of this study was to investigate the applicability of an innovative continuous manufacturing system for semi-solid and liquid pharmaceutical formulations. A commercially available pharmaceutical oral suspension was selected as model formulation. Premixes of the raw materials were dosed...
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A Continuous Operation Concept for a Rotary Tablet Press Using Mass Flow Operating Points
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Martinetz, Michael Christian, Rehrl, Jakob Aigner, Isabella Sacher, Stephan, Khinast, Johannes
Abstract In a continuous pharmaceutical manufacturing line the rotary tablet press was viewed as the master of control concept and defined the mass flow through the entire process. According to a conventional control concept, missing mass flow from an upstream unit operation leads to a shutdown...
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A flowsheet model for the development of a continuous process for pharmaceutical tablets: An industrial perspective
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Garcia-Munoz, Salvador, Butterbaugh, Adam Leavesley, Ian Manley, Leo Francis, Slade, David, Bermingham, Sean
A dynamic model of a continuous direct compression process for pharmaceutical tablets is presented. The objective is to assess the impact of the variability from the feeder system on the concentration of drug in the powder in the feed frame of a tablet press. The model is based on principles of...
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A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, M, Singh, R, Ramachandran, R
In this work, a hybrid MPC (model predictive control)-PID (proportional-integral-derivative) control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs). The specific unit operations associated with the purification and...
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A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, M, Singh, R, Ramachandran, R
In this work, a hybrid MPC (model predictive control)-PID (proportional-integral-derivative) control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs). The specific unit operations associated with the purification and...
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A large-scale experimental comparison of batch and continuous technologies in pharmaceutical tablet manufacturing using ethenzamide
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Matsunami, Kensaku, Nagato, Takuya, Hasegawa, Koji, Sugiyama, Hirokazu
This paper compares batch and continuous technologies in terms of product quality and process performance in pharmaceutical tablet manufacturing using ethenzamide as the active pharmaceutical ingredient. Batch and continuous processes using wet granulation were investigated by performing...
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A model-based framework for design and analysis of PAT systems
09 Jun 2023 | Workshop | Contributor(s): Gani, Rafiqul, Singh, Ravendra, Gernaey, Krist
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A multi-scale hybrid CFD-DEM-PBM description of a fluid-bed granulation process
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, Maitraye, Barrasso, Dana Singh, Ravendra, Ramachandran, Rohit
In this study, a hybrid multi-scale model has been developed for a continuous fluid bed wet granulation process by dynamically coupling computational fluid dynamics (CFD) with a discrete element model (DEM) and population balance model (PBM). In this process, the granules are formed by spraying...
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A multivariate approach to predict the volumetric and gravimetric feeding behavior of a low feed rate feeder based on raw material properties
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bostijn, N, Dhondt, J, Ryckaert, A, Szabo, E, Dhondt, W, Van Snick, B, Vanhoorne, V, Vervaet, C, De Beer, T
In this study, the volumetric and gravimetric feeding behavior of 15 pharmaceutical powders on a low feed rate feeder was correlated with their material properties through a multivariate approach. The powders under investigation differ substantially in terms of material properties, making the...
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A New Software Framework for Implementing Crystal Growth Models to Materials of Any Crystallographic Complexity
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Zhao, Yongsheng, Tilbury, Carl J. Landis, Steven Sun, Yuanyuan, Li, Jinjin, Zhu, Peng, Doherty, Michael F.
To continue the realization of new therapeutics, a more diverse range of solid forms is being considered. Synthetic modalities are broadening beyond simple organic molecules to more complicated structures, including organic salts, cocrystals, and solvates. As in all crystalline applications,...
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A NIR-Based Study of Desorption Kinetics during Continuous Spin Freeze-Drying
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Leys, Laurens, Nuytten, Gust, Lammens, Joris, Van Bockstal, Pieter-Jan, Corver, Jos, Vervaet, Chris, De Beer, Thomas
The pharmaceutical industry is progressing toward the development of more continuous manufacturing techniques. At the same time, the industry is striving toward more process understanding and improved process control, which requires the implementation of process analytical technology tools (PAT)....
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A Novel Integrated Workflow for Isolation Solvent Selection Using Prediction and Modeling
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ottoboni, S, Wareham, BVassileiou, A, Robertson, M, Brown, CJ, Johnston, B, Price, CJ
A predictive tool was developed to aid process design and to rationally select optimal solvents for isolation of active pharmaceutical ingredients. The objective was to minimize the experimental work required to design a purification process by (i) starting from a rationally selected...
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A novel robust digital design of a network of industrial continuous cooling crystallizers of dextrose monohydrate: From laboratory experiments to industrial application
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Nagy, Zoltan K., Szilagyi, Botond Pal, Kanjakha, Tabar, Iman Beheshti ;
This paper presents the first-ever industrial application of the digital design of a complex, large-scale industrial continuous crystallization network. The aim of the work is to optimize a large-scale continuous crystallization network used for the purification of dextrose monohydrate, by...
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A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Leys, L., Vanbillemont, B., Van Bockstal, P. J., Lammens, J., Nuytten, G., Corver, J., Vervaet, C., De Beer, T.
An innovative continuous spin-freeze-drying technology for unit doses was recently developed. For this technology, a mechanistic primary drying model was developed allowing the calculation of the optimal dynamic drying trajectory for spin-frozen formulations. In this work, a model-based and...
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A Process for the Formation of Nanocrystals of Active Pharmaceutical Ingredients with Poor Aqueous Solubility in a Nanoporous Substrate
09 Jun 2023 | Peer-reviewed journal | Contributor(s): O'Mahony, M, Leung, AKFerguson, S, Trout, BL, Myerson, AS
A potential process for the formation of nanocrystals of the poorly soluble drug, ibuprofen, within a nanoporous material is demonstrated. Nanocrystalline ibuprofen (IBP) is prepared at <= 106 nm by adding a solution containing IBP to particles of controlled pore glass (CPG) within a column so...
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A retrofit strategy to achieve “Fast, Flexible, Future (F3)” pharmaceutical production processes
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Rozada-Sanchez, Raquel Wrate, Tim Muller, Frans Gernaey, Krist V Gani, Rafiqul, Woodley, John M
n the work reported here, a substrates adoption methodology for a series of similar substrates has been developed as part of a retrofit strategy. The objective is to achieve “fast, flexible and future” pharmaceutical production processes by adapting a generic modular process-plant template....
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A Stochastic Population Balance Equation Model for Nucleation and Growth of Crystals with Multiple Polymorphs
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Maggioni, Giovanni, Mazzotti, Marco
Understanding polymorph crystallization is important due to the different properties, such as bioavailability or crystal shape, exhibited by the different crystal forms. In this work, we present a model, based on population balance equations, describing the unseeded crystallization by cooling of...
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A Structured Approach To Cope with Impurities during Industrial Crystallization Development
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Urwin, SJ, Levilain, GMarziano, I, Merritt, JM, Houson, I, Ter;Horst, JH
The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to...
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A Study on In-Line Tablet Coating-the Influence of Compaction and Coating on Tablet Dimensional Changes
09 Jun 2023 | Peer-reviewed journal | Contributor(s): Cahyadi, C., Tan, B. X., Chan, L. W., Heng, P. W. S.
Prior to coating, tablets are usually stored for a definite period to enable complete strain recovery and prevent subsequent volumetric expansion-related coating defects. In-line coating is defined as the coating of tablets immediately after compaction. In-line coating will be expected to improve...
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A systematic computer aided framework for design and analysis of PAT systems
09 Jun 2023 | Workshop | Contributor(s): Gernaey, Krist, Singh, Ravendra, Gani, Rafiqul
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