Expedient preparation of active pharmaceutical ingredient ketamine under sustainable continuous flow conditions

09 Jun 2023 | Contributor(s): Kassin, VEH, Gerardy, RToupy, T, Collin, D, Salvadeo, E, Toussaint, F, Van, Hecke, K, Monbaliu, JCM

A robust three-step continuous flow procedure is presented for the efficient and sustainable preparation of active pharmaceutical ingredient ketamine. The procedure relies on the main assets of continuous flow processing, starts from commercially available chemicals, utilizes low toxicity...

Experimental determination of residence time distribution in continuous dry granulation

09 Jun 2023 | Contributor(s): Mangal, Haress, Kleinebudde, Peter

With increasing importance of continuous manufacturing, the interest in integrating dry granulation into a continuous manufacturing line is growing. Residence time distribution measurements are of importance as they provide information about duration of materials within the process. These data...

Experimental investigation and modelling of tensile strength of pharmaceutical tablets based on shear force applied by feed frame paddles

09 Jun 2023 | Contributor(s): Furukawa, Ryoichi, Singh, Ravendra, Ierapetritou, Marianthi

The feed frame is an essential device used in a rotary tablet press and it improves the performance of the powder filling process into dies. However, the feed frame affects critical quality attributes such as a tensile strength and a dissolution negatively due to a shear applied to powders from...

Experimental study of the stirring conditions taking place in a pilot plant continuous mixer of particulate solids

09 Jun 2023 | Contributor(s): Marikh, K, Berthiaux, H, Mizonov, V, Barantsev, E

This work focuses on the characterisation and quantification of the stirring action that takes place inside a continuous mixer of particulate solids, under several operating conditions. Pure products, as well as 50% mass mixtures, are investigated to provide a basis for a better prediction of the...

Exploratory studies in heat-assisted continuous twin-screw dry granulation: A novel alternative technique to conventional dry granulation

09 Jun 2023 | Contributor(s): Kallakunta, Venkata Raman, Patil, Hemlata, Tiwari, Roshan, Ye, Xingyou, Upadhye, Sampada, Vladyka, Ronald S., Sarabu, Sandeep, Kim, Dong Wuk, Bandari, Suresh, Repka, Michael A.

Dry granulation is the preferred technique for solvent-sensitive products, especially drugs with stability problems such as hydrolysis. Twin-screw granulation is a continuous granulation technique, offering a potential alternative to conventional dry granulation techniques such as roller...

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 Claisen condensation reaction optimization in a continuous flow reactor

25 Jun 2024 | Contributor(s): Michałek, Stanisław, Powała, Antoni, Gurba-Bryśkiewicz, Lidia, Piórkowska, Natalia, Olejkowska, Patrycja, Yamani, Abdellah, Ochal, Zbigniew, Dubiel, Krzysztof, Wieczorek, Maciej

In our previous study, we described the batch synthesis of CPL304110, an innovative pan-FGFR inhibitor. Herein, we transferred the Claisen condensation reaction, one of the synthesis steps to a continuous flow reactor. A simple solvent switch from ethanol to tetrahydrofuran shortened the original...

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

Five key factors to consider when selecting a granulation system for tablet manufacturing

23 Jan 2024 | Magazine | Contributor(s): Fi Forrest

Granulation is a vital process in pharmaceutical dosage forms, transforming powders into granules. Michael Schupp from Gerteis - specialists in dry granulation systems for the pharmaceutical industry - discusses what you should be looking for when choosing your granulation method. 

Flash Chemistry Approach to Organometallic C-Glycosylation for the Synthesis of Remdesivir

25 Jun 2024 | Peer-reviewed journal | Contributor(s): Keutz, Timo von, Williams, Jason D., Kappe, C. Oliver

In a rapidly changing environment, such as the current COVID-19 pandemic, continuous flow reactors bear the potential to increase the production of urgently needed active pharmaceutical ingredients (APIs) on demand. In the synthesis of remdesivir, the organometallic C-glycosylation step was...

Flexibility in Drug Product Development: A Perspective

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kapoor, Yash, Ferguson, Heidi, Skomski, Daniel, Daublain, Pierre, Troup, Gregory, Dalton, Chad, Ramasamy, Manoharan, Templeton, Allen

The process of bringing a drug to market involves innumerable decisions to refine a concept into a final product. The final product goes through extensive research and development to meet the target product profile and to obtain a product that is manufacturable at scale. Historically, this...

Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals

09 Jun 2023 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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 | Peer-reviewed journal | 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...