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...

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...

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...

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...

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...

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...

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...

A framework of hybrid model development with identification of plant-model mismatch

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Chen, Yingjie, Ierapetritou, Marianthi

Abstract Hybrid modeling has attracted increasing attention in order to take advantage of the additional data to improve process understanding. Current practice often adopts mechanistic models to predict process behaviors. These mechanistic models are based on physical understandings and...

A hybrid model for multipoint real time potency observation in continuous direct compression manufacturing operations

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Gallo-Molina, Juan Pablo, Cogoni, Giuseppe, Peeters, Elisabeth, Rao Ambati, Seshagiri, Nopens, Ingmar

The ongoing transition from batch to continuous manufacturing offers both challenges and opportunities in the field of oral solid dosage form production. In turn, Process Analytical Technology (PAT) offers a path towards the successful deployment of continuous tablet manufacturing in rotary...

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...

A hybrid NIR-soft sensor method for real time in-process control during continuous direct compression manufacturing operations

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Cogoni, Giuseppe, Husain, Anas, Alam, Md Anik, Liu, Yang Angela, Kamyar, Reza

Near Infrared (NIR) spectroscopy is commonly utilized for continuous manufacturing as Process Analytical Technology (PAT) tool. This paper focus on a continuous direct compression manufacturing process, in which an NIR PAT probe is integrated into the tablet press feed frame and into the tablet...

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...

A model-based framework for design and analysis of PAT systems

09 Jun 2023 | Workshop | Contributor(s): Gani, Rafiqul, Singh, Ravendra, Gernaey, Krist

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...

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...

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)....

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...

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....

A review of PAT strategies in secondary solid oral dosage manufacturing of small molecules

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Laske, Stephan, Paudel, Amrit, Scheibelhofer, Otto, Sacher, Stephan, Hoermann, Theresa, Khinast, Johannes, Kelly, Adrian, Rantannen, Jukka, Korhonen, Ossi, Stauffer, Fanny, De Leersnyder, Fien, De Beer, Thomas, Mantanus, Jerome, Chavez, Pierre-Francois, Thoorens, Benjamin, Ghiotti, Patrizia, Schubert, Martin, Tajarobi, Pirjo, Haeffler, Gunnar, Lakio, Satu, Fransson, Magnus, Sparen, Anders, Abrahmsen-Alami, Susanna, Folestad, Staffan, Funke, Adrian, Backx, Ivo, Kavsek, Barbara, Kjell, Francois, Michaelis, Marc, Page, Trevor, Palmer, John, Schaepman, Alexander, Sekulic, Sonja, Hammond, Steve, Braun, Birgit, Colegrove, Brenda

Pharmaceutical solid oral dosage product manufacturing is a well-established, yet revolutionizing area. To this end, process analytical technology (PAT) involves interdisciplinary and multivariate (chemical, physical, microbiological and mathematical) methods for material (e.g. materials,...

A sampling system for flowing powders based on the theory of sampling

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Alvarado-Hernández, Bárbara B, Sierra-Vega, Nobel O, Martínez-Cartagena, Pedro, Hormaza, Manuel, Méndez, Rafael, Romañach, Rodolfo J.

An innovative chute and stream sampler system for flowing powders has been developed and tested. The system is designed for representative sampling based on the principles of the Theory of Sampling (TOS). The sampling system was used in combination with near infrared (NIR) spectroscopy to...

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...

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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A Systematic Framework for Data Management and Integration in a Continuous Pharmaceutical Manufacturing Processing Line

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Cao, Huiyi, Mushnoori, Srinivas, Higgins, Barry, Kollipara, Chandrasekhar, Fermier, Adam, Hausner, Douglas, Jha, Shantenu, Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

As the pharmaceutical industry seeks more efficient methods for the production of higher value therapeutics, the associated data analysis, data visualization, and predictive modeling require dependable data origination, management, transfer, and integration. As a result, the management and...

A systematic framework for onsite design and implementation of a control system in a continuous tablet manufacturing process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Sahay, Abhishek Muzzio, Fernando Ierapetritou, Marianthi, Ramachandran, Rohit

A novel manufacturing strategy based on continuous processing integrated with online/inline monitoring tools coupled with an advanced control system is highly desired for efficient Quality by Design (QbD)-based pharmaceutical manufacturing. A control system ensures the predefined end product...