Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals

09 Jun 2023 | Contributor(s): Kern, Simon, Wander, Lukas, Meyer, Klas, Guhl, Svetlana, Gottu Mukkula, Anwesh, Holtkamp, Manuel, Salge, Malte, Fleischer, Christoph, Weber, Nils, King, Rudibert, Engell, Sebastian, Paul, Andrea, Pereira Remelhe, Manuel, Maiwald, Michael

Modular plants using intensified continuous processes represent an appealing concept for the production of pharmaceuticals. It can improve quality, safety, sustainability, and profitability compared to batch processes; besides, it enables plug-and-produce / reconfiguration for fast product...

Flow and bulk density enhancements of pharmaceutical powders using a conical screen mill: A continuous dry coating device

09 Jun 2023 | Contributor(s): Huang, ZH, Scicolone, JV, Gurumuthy, L, Dave, RN

The conical screen mill or Comil, a powder delumping device, was investigated due to its recent success as a continuously operated dry coater, The improvements in packing and flowability for different size grades of active pharmaceutical ingredients (APls) (acetaminophen, ibuprofen, and ascorbic...

Flow Chemistry, Continuous Processing, and Continuous Manufacturing: A Pharmaceutical Perspective

09 Jun 2023 | Contributor(s): May, SA

Flow chemistry has become a vibrant area for Research Article over the past decade. This perspective is intended to capture insights on how these advances have and will continue to impact the development and commercialization of active pharmaceutical ingredients. A series of chemistry examples...

Flow Chemistry: Recent Developments in the Synthesis of Pharmaceutical Products

09 Jun 2023 | Contributor(s): Porta, R, Benaglia, M, Puglisi, A

Recently, application of the flow technologies for the preparation of fine chemicals, such as natural products or Active Pharmaceutical Ingredients (APIs), has become very popular, especially in academia. Although pharma industry still relies on multipurpose batch or semibatch reactors, it is...

Flow chemistryMicroreaction technology comes of age

09 Jun 2023 | Contributor(s): Jensen, KF

Over the past two decades, microreaction technology has matured from early devices and concepts to encompass a wide range of commercial equipment and applications. This evolution has been aided by the confluence of microreactor development and adoption of continuous flow technology in organic...

Flow Processing as a Tool for API Production in Developing Economies

09 Jun 2023 | Contributor(s): de;Souza, ROMA, Watts, P

In this perspective article, the use of continuous flow synthesis to prepare advanced pharmaceutical intermediates in developing economies is highlighted. Case studies are presented to suggest that cost effective local manufacture of life saving drugs, may potentially be implemented to facilitate...

Flow synthesis kinetics for lomustine, an anti-cancer active pharmaceutical ingredient

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

Continuous flow synthesis of active pharmaceutical ingredients (APIs) can offer access to process conditions that are otherwise hazardous when operated in batch mode, resulting in improved mixing and heat transfer, which enables higher yields and greater reaction selectivity. Reaction kinetic...

Flowsheet modeling of a continuous direct compression process

09 Jun 2023 | Contributor(s): Yoon, Seongkyu, Galbraith, Shaun, Cha, Bumjoon, Liu, Huolong

Continuous manufacturing for the production of pharmaceutical products is emerging as a key technology due to the advantages it has over traditional batch manufacturing methods. Process systems engineering is critical in rolling out this technology within the industry since it allows for more...

Flowsheet Models Modernize Pharmaceutical Manufacturing Design and Risk Assessment

09 Jun 2023 | Contributor(s): Muzzio, Fernando, Singh, M Sebastian Escotet-Espinoza Ravendra, Lee Sau, Thomas O’Connor Marianthi, Ierapetritou, Lee Sharmista Chatterjee Rohit Ramachandran, Sen, Maitraye

The pharmaceutical industry has recognized the value of implementing a systematic approach to drug product development where quality is built into the product and process. The FDA initiative on quality by design (QbD) promotes the design of the product and manufacturing process using principles...

Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation

09 Jun 2023 | Contributor(s): Sen, Maitraye, Rogers, Amanda Singh, Ravendra Chaudhury, Anwesha John, Joyce Ierapetritou, Marianthi G, Ramachandran, Rohit

In this work, a continuous API purification process has been optimized using an integrated flowsheet model. The simulation is dynamic in nature and includes an API purification step (crystallization), followed by filtration, drying and mixing of the API with an excipient. For the first time, this...

Fluidization characterization in the ConSigma 25 dryer via process data - A method of advanced quality assurance in continuous manufacturing

09 Jun 2023 | Contributor(s): Rehrl, Jakob, Hoermann-Kincses, Theresa, Sibanc, Rok, Hsiao, Wen-Kai, Franke, Meik, Khinast, Johannes

Wet granulation lines in pharmaceutical manufacturing facilities typically comprise a dryer that removes the excess moisture content after wet granulation. In this study, a semi-continuous dryer installed in the ConsiGma 25 wet granulation line was investigated. The goal was to highlight specific...

Exploring the Role of Anti-solvent Effects during Washing on Active Pharmaceutical Ingredient Purity

09 Jun 2023 | Contributor(s): Shahid, M, Sanxaridou, GOttoboni, S, Lue, L, Price, C

Washing is a key step in pharmaceutical isolation to remove the unwanted crystallization solvent (mother liquor) from the active pharmaceutical ingredient (API) filter cake. This study looks at strategies for optimal wash solvent selection, which minimizes the dissolution of API product crystals...

Fast Offset-Free Nonlinear Model Predictive Control Based on Moving Horizon Estimation

09 Jun 2023 | Contributor(s): Huang, Rui, Biegler, Lorenz T., Patwardhan, Sachin C.

To deal with plant-model mismatches in control practice, this paper proposes two variations of an offset-free framework which integrates nonlinear model predictive control (NMPC) and moving horizon estimation (MHE). We prove that the proposed method achieves offset-free regulatory behavior, even...

Faster to First-time-in-Human: Prediction of the liquid solid ratio for continuous wet granulation

09 Jun 2023 | Contributor(s): Junnila, A, Wikstrom, HMegarry, A, Gholami, A, Papathanasiou, F, Blomberg, A, Ketolainen, J, Tajarobi, P

In early development, when active pharmaceutical ingredient (API) is in short supply, it would be beneficial to reduce the number of experiments by predicting a suitable L/S ratio before starting the product development. The aim of the study was to decrease development time and the amount of API...

Feasibility of Using Light-Induced Fluorescence Spectroscopy for Low-Dose Formulations Monitoring and Control

09 Jun 2023 | Contributor(s): Igne, Benoît, Baldasano, Caitlin, Airiau, Christian

Purpose: Light-induced fluorescence was evaluated as a process analytical tool in the development of quantitative models for themonitoring of a low-dose formulation manufacturing process. Method: The system, equipped with a probe, was positioned in a tablet press feed-frame to monitor the active...

Feed frame: The last processing step before the tablet compaction in pharmaceutical manufacturing

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel, Romañach, Rodolfo J., Méndez, Rafael

The feed frame is a force-feeding device used in the die filling process. The die filling process is crucial within pharmaceutical manufacturing to guarantee the critical quality attributes of the tablets. In recent years, interest in this unit has increased because it can affect the properties...

Feedback in Flow for Accelerated Reaction Development

09 Jun 2023 | Contributor(s): Reizman, BJ, Jensen, KF

The pharmaceutical industry is investing in continuous flow and high-throughput experimentation as tools for rapid process development accelerated scale-up. Coupled with automation, these technologies offer the potential for comprehensive reaction characterization and optimization, but with the...

Feeding of particle-based materials in continuous solid dosage manufacturing: a material science perspective

09 Jun 2023 | Contributor(s): Hsiao, WK, Hormann, TR, Toson, P, Paudel, A, Ghiotti, P, Stauffer, F, Bauer, F, Lakio, S, Behrend, O, Maurer, R, Holman, J, Khinast, J

The pharmaceutical industry today is experiencing a paradigm shift from batch to continuous manufacturing, which promises greater flexibility to target diverse populations, as well as more-consistent product quality to ensure best efficacy. However, shifting to continuous processing means that...

Feedrate deviations caused by hopper refill of loss-in-weight feeders

09 Jun 2023 | Contributor(s): William E. Engisch, Fernando J. Muzzio 

Continuous powder processing requires accurate and consistent feed streams of the raw materials which makes loss-in-weight feeders invaluable. Periodic hopper refill of the feeders, which is needed for continuous operation, can lead to inconsistent and poor feeding performance. This paper...

Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes

09 Jun 2023 | Contributor(s): Chen, Liang, He, Zizhou, Kunnath, Kuriakose, Zheng, Kai, Kim, Sangah, Dave, Rajesh N.

Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid...

Fines removal in a continuous plug flow crystallizer by optimal spatial temperature profiles with controlled dissolution

09 Jun 2023 | Contributor(s): Majumder, Aniruddha, Nagy, Zoltan K.

This work presents a systematic study for obtaining the optimal temperature profile in a continuous plug flow crystallizer (PFC). The proposed PFC consists of multiple segments where the temperature of each segment can be controlled individually. An optimization problem is formulated for a target...

First-principles and direct design approaches for the control of pharmaceutical crystallization

09 Jun 2023 | Contributor(s): Fujiwara, Mitsuko, Nagy, Zoltan K. Chew, Jie W., Braatz, Richard D. ;

Crystallization is the main separation and purification process for the manufacturing of drug substances. Not only does crystallization affect the efficiency of downstream operations such as filtering, drying, and formulating, the efficacy of the drug can be dependent on the final crystal form....

Fit-for-Purpose Miniature NIR Spectroscopy for Solid Dosage Continuous Manufacturing

09 Jun 2023 | Contributor(s): Karry, Krizia, Singh, Ravendra, Muzzio, Fernando

Evaluation of Hot-Melt Extrusion and Injection Molding for Continuous Manufacturing of Immediate-Release Tablets

09 Jun 2023 | Contributor(s): Melocchi, Alice, Loreti, Giulia, Del Curto, Maria Dorly, Maroni, Alessandra, Gazzaniga, Andrea, Zema, Lucia

The exploitation of hot-melt extrusion and injection molding for the manufacturing of immediate-release (IR) tablets was preliminarily investigated in view of their special suitability for continuous manufacturing, which represents a current goal of pharmaceutical production because of its...

Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses

09 Jun 2023 | Contributor(s): De Meyer, L., Van Bockstal, P. -J., Corver, J., Vervaet, C., Remon, J. P., De Beer, T.

Spin-freezing as alternative freezing approach was evaluated as part of an innovative continuous pharmaceutical freeze-drying concept for unit doses. The aim of this paper was to compare the sublimation rate of spin-frozen vials versus traditionally frozen vials in a batch freeze-dryer, and its...