Determination of a quantitative relationship between material properties, process settings and screw feeding behavior via multivariate data-analysis

09 Jun 2023 | 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...

Determination of Residence Time Distribution in a Continuous Powder Mixing Process With Supervised and Unsupervised Modeling of In-line Near Infrared (NIR) Spectroscopic Data

09 Jun 2023 | Contributor(s): Pedersen, Troels, Karttunen, Anssi-Pekka, Korhonen, Ossi, Wu, Jian Xiong, Naelapää, Kaisa, Skibsted, Erik, Rantanen, Jukka

Successful implementation of continuous manufacturing processes requires robust methods to assess and control product quality in a real-time mode. In this study, the residence time distribution of a continuous powder mixing process was investigated via pulse tracer experiments using near infrared...

Determination of the kinetic parameters for the crystallization of paracetamol from water using metastable zone width experiments

09 Jun 2023 | Contributor(s): Nagy, Zoltan K., Fujiwara, Mitsuko Woo, Xing Yi, Braatz, Richard D. ;

A new approach for the estimation of kinetic parameters of crystallization from data obtained during the determination of metastable zone width is presented. The method is based on a simplified dynamic model of the system, which combines the population balance and mass balance, as well as...

Determining key parameters of continuous wet granulation for tablet quality and productivity: A case in ethenzamide

09 Jun 2023 | Contributor(s): Matsunami, K, Nagato, THasegawa, K, Sugiyama, H

This paper aims to determine key parameters that affect tablet quality and productivity in continuous tablet manufacturing. Experiments were performed based on design of experiments using a continuous high-shear granulator and ethenzamide as the active pharmaceutical ingredient. To guide a...

Developing a Batch Isolation Procedure and Running It in an Automated Semicontinuous Unit: AWL CFD25 Case Study

09 Jun 2023 | Contributor(s): Ottoboni, S, Shahid, MSteven, C, Coleman, S, Meehan, E, Barton, A, Firth, P, Sutherland, R, Price, CJ

A key challenge during the transition from laboratory/small batch to continuous manufacturing is the development of a process strategy that can easily be adopted for a larger batch/continuous process. Industrial practice is to develop the isolation strategy for a new drug/process in batch using...

Developing a framework to model the primary drying step of a continuous freeze-drying process based on infrared radiation

09 Jun 2023 | Contributor(s): Van Bockstal, Pieter-Jan, Corver, Jos, Mortier, Severine Therese F. C., De Meyer, Laurens, Nopens, Ingmar, Gernaey, Krist V., De Beer, Thomas

The continuous freeze-drying concept based on spinning the vials during freezing and on non-contact energy transfer via infrared (IR) radiation during drying, improves process efficiency and product quality (uniformity) compared to conventional batch freeze-drying. Automated control of this...

Development and Application of a Business Case Model for a Stream Sampler in the Pharmaceutical Industry

09 Jun 2023 | Contributor(s): Fontalvo-Lascano, María A, Alvarado-Hernández, Bárbara B., Conde, Carlos, Sánchez, Eric J., Méndez-Piñero, Mayra I., Romañach, Rodolfo

Purpose: A template to prepare a business case for Process Analytical Technology (PAT) and Continuous Manufacturing (CM) projects is presented in this study. Business cases are necessary tools used in different organizations to present new projects for management evaluation. As new ways of...

Development and applications of a material library for pharmaceutical continuous manufacturing of solid dosage forms

09 Jun 2023 | Contributor(s): Yifan Wang, ThomasO'Connor, TianyiLi, Muhammad Ashraf

The purpose of this study is to establish a material library and discuss its potential application to the development and lifecycle management of a continuous manufacturing process for solid dosage forms. Particularly, this study addresses the importance of selecting process-relevant testing...

Development and Characterization of a Single Stage Mixed-Suspension, Mixed-Product-Removal Crystallization Process with a Novel Transfer Unit

09 Jun 2023 | Contributor(s): Hou, GY, Power, GBarrett, M, Glennon, B, Morris, G, Zhao, Y

A continuously operated single stage mixed-suspension, mixed-product-removal (MSMPR) crystallizer using intermittent withdrawal via a dip pipe with combined pressure/vacuum was successfully developed for the manufacture of active pharmaceutical ingredients. Approximately 5.8% of the total...

Cyber-physical-based PAT (CPbPAT) framework for Pharma 4.0

09 Jun 2023 | Contributor(s): Barenji, Reza Vatankhah, Akdag, Yagmur, Yet, Barbaros., Oner, Levent

Industry 4.0 aims to integrate manufacturing operations into a seamless digital whole by incorporating flexibility, agility, re-configurability, and sustainability. The result of this integration is a “smart factory” that is more lean, agile, and flexible in operations. There are valid reasons,...

Data reconciliation in the Quality-by-Design (QbD) implementation of pharmaceutical continuous tablet manufacturing

09 Jun 2023 | Contributor(s): Su, Qinglin, Bommireddy, Yasasvi, Shah Yash, Ganesh, Sudarshan, Moreno, Mariana, Liu, Jianfeng, Gonzalez, Marcial, Yazdanpanah, Nima, O'Connor, Thomas, Reklaitis, Gintaras V., Nagy, Zoltan K

Data provided by in situ sensors is always affected by some level of impreciseness as well as uncertainty in the measurements due to process operation disturbance or material property variance. In-process data precision and reliability should be considered when implementing active product quality...

Deep learning for continuous manufacturing of pharmaceutical solid dosage form

09 Jun 2023 | Contributor(s): Roggo, Yves, Jelsch, Morgane, Heger, Philipp, Ensslin, Simon, Krumme, Markus

Continuous Manufacturing (CM) of pharmaceutical drug products is a new approach within the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line for production of solid dosage forms was investigated. The line was composed of the subsequent continuous unit:...

Deep UV Raman and fluorescence spectroscopy for real-time in situ process monitoring

09 Jun 2023 | Contributor(s): Hug, WF, Nguyen, QReid, M, Sijapati, K, Reid, RD

Raman spectroscopy has become an increasingly common analytical method for real-time, on-line, in-line, and off-line in situ monitoring of product quality in a variety of pharmaceutical, chemical, and biological manufacturing environments, including wastewater quality [1]. The major shortcomings...

Design and Commercialization of an End-to-End Continuous Pharmaceutical Production Process: A Pilot Plant Case Study

09 Jun 2023 | Contributor(s): Testa, Christopher J., Hu, Chuntian, Shvedova, Khrystyna, Wu, Wei, Sayin, Ridade, Casati, Federica, Halkude, Bhakti S., Hermant, Paul, Shen, Dongying Erin, Ramnath, Anjana, Su, Qinglin, Born, Stephen C., Takizawa, Bayan, Chattopadhyay, Saptarshi, O'Connor, Thomas F., Yang, Xiaochuan, Ramanujam, Sukumar, Mascia, Salvatore

The pharmaceutical industry faces multiple challenges (e.g., inefficient manufacturing techniques, quality control issues, and supply chain vulnerabilities) because of its current batch-wise approach to manufacturing. Recent regulatory support for continuous manufacturing and advances in...

Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate

09 Jun 2023 | Contributor(s): Christensen, KM, Pedersen, MJDam-Johansen, K, Holm, TL, Skovby, T, Kiil, S

A novel filter reactor system for continuous production of selected pharmaceutical intermediates is presented and experimentally verified. The filter reactor system consists of a mixed flow reactor equipped with a bottom filter, to retain solid reactant particles, followed by a conventional plug...

Design and optimization of a multistage continuous cooling mixed suspension, mixed product removal crystallizer

09 Jun 2023 | Contributor(s): Power, Graham, Hou, Guangyang Kamaraju, Vamsi Krishna Morris, Gary, Zhao, Yan, Glennon, Brian

Continuously operated single and multistage MSMPR crystallizers using intermittent withdrawal through use of an automated pressure supply were developed for the cooling crystallization of Paracetamol from an aqueous isopropanol mixture. The onset of steady state was detected through analysis of...

Design of an Integrated Continuous Manufacturing System

09 Jun 2023 | Contributor(s): Oka, Sarang S, Escotet-Espinoza, M Sebastian Singh, Ravendra Scicolone, James V Hausner, Douglas B Ierapetritou, Marianthi, Muzzio, Fernando J

This chapter presents a systematic, 12-step approach for designing, implementing, integrating, optimizing, and validating a continuous manufacturing system. Wherever appropriate, it also discusses the regulatory relevance of the technology integration effort. When considering the development of a...

Design of Condition-based Maintenance Framework for Process Operations Management in Pharmaceutical Continuous Manufacturing

09 Jun 2023 | Contributor(s): Ganesh, Sudarshan, Su, Qinglin, Vo, Le Bao Dan, Pepka, Nolan, Rentz, Benjamin, Vann, Lucas, Yazdanpanah, Nima, O'Connor, Thomas, Nagy, Zoltan K., Reklaitis, Gintaras V.

Continuous manufacturing, an emerging technology in the pharmaceutical industry, has the potential to increase the efficiency, and agility of pharmaceutical manufacturing processes. To realize these potential benefits of continuous operations, effectively managing materials, equipment, analyzers,...

Design Space Identification and Visualization for Continuous Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Diab, S, Gerogiorgis, DI

Progress in continuous flow chemistry over the past two decades has facilitated significant developments in the flow synthesis of a wide variety of Active Pharmaceutical Ingredients (APIs), the foundation of Continuous Pharmaceutical Manufacturing (CPM), which has gained interest for its...

Designing a novel continuous manufacturing plant with superior monitoring and control

09 Jun 2023 | Contributor(s): Singh, Ravendra, Zhang, Jun Ierapetritou, Marianthi, Ramachandran, Rohit

There is a growing interest in manufacturing the pharmaceutical product continuously . Along with other advantages , it provides an appropriate platform to implement suitable monitoring and control architecture, to improve the product quality and minimise product rejection and operating expenses....

Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins

09 Jun 2023 | Contributor(s): Bloomquist, CJ, Mecham, MBParadzinsky, MD, Janusziewicz, R, Warner, SB, Luft, JC, Mecham, SJ, Wang, AZ, DeSimone, JM

Mass customization along with the ability to generate designs using medical imaging data makes 3D printing an attractive method for the fabrication of patient-tailored drug and medical devices. Herein we describe the application of Continuous Liquid Interface Production (CLIP) as a method to...

Converting a batch based high -shear granulation process to a continuous dry granulation process; a demonstration with ketoprofen tablets

09 Jun 2023 | Contributor(s): Taipale-Kovalainen, Krista, Ketolainen, Jarkko, Korhonen, Ossi, Ervasti, Tuomas

When one wishes to convert a batch based manufacturing process of an existing tablet product to a continuous process, there are several available strategies which can be adopted. Theoretically, the most straightforward way would be to proceed with the corresponding processing principles, for...

Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Active Pharmaceutical Ingredients

09 Jun 2023 | Contributor(s): Badruddoza, AM, Godfrin, PDMyerson, AS, Trout, BL, Doyle, PS

Although roughly 40% of pharmaceuticals being developed are poorly water soluble, this class of drugs lacks a formulation strategy capable of producing high loads, fast dissolution kinetics, and low energy input. In this work, a novel bottom-up approach is developed for producing and formulating...

Coupling hot melt extrusion and fused deposition modeling: Critical properties for successful performance

09 Jun 2023 | Contributor(s): Bandari, Suresh, Nyavanandi, Dinesha, Dumpa, Nagireddy, Repka, Michael A.

Interest in 3D printing for pharmaceutical applications has increased in recent years. Compared to other 3D printing techniques, hot melt extrusion (HME)-based fused deposition modeling (FDM) 3D printing has been the most extensively investigated for patient-focused dosage. HME technology can be...

Cross-Pharma Collaboration for the Development of a Simulation Tool for the Model-Based Digital Design of Pharmaceutical Crystallization Processes (CrySiV)

09 Jun 2023 | Contributor(s): Szilagyi, Botond, Wu, Wei Lee Eren, Ayse Mackey, Jaron, Kshirsagar, Shivani, Szilagyi, Emoke, Ostergaard, Iben, Qu, Haiyan, Sinha, Kushal, Mlinar, Laurie, Pohlman, Daniel, Chen, Jie, Nere, Nandkishor, Boukerche, Moussa, Korde, Akshay, Ellis, Ryan, Lovette, Michael, Black, Simon, Jawor-Baczynska, Anna, Li, Huayu, Yang, Bing Shiou, Irdam, Erwin, Patience, Daniel, McKeown, Rahn, Ketchum, Megan, Green, Daniel A., Reddy, Venkata Ramana, Polster, Christopher, Burcham, Christopher, Jarmer, Daniel, Merritt, Jeremy Miles, Cote, Aaron, Sirota, Eric, Codan, Lorenzo, Schoell, Jochen, Liu, Yiqing Claire, Girard, Kevin P., Kulkarni, Samir A., Yang, Yihui, Quon, Justin L., Nagy, Zoltan K.

Precompetitive collaborations on new enabling technologies for Research Article and development are becoming popular among pharmaceutical companies. The Enabling Technologies Consortium (ETC), a precompetitive collaboration of leading innovative pharmaceutical companies, identifies and executes...