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...

Flow-oriented synthetic design in the continuous preparation of the aryl piperazine drug flibanserin

10 May 2024 | Contributor(s): Bana, Péter, Szigetvári, Áron, Kóti, János, Éles, János, Greiner, István

An uninterrupted, four-step continuous-flow sequence was developed for the preparation of the aryl piperazine-type serotonin receptor modulator drug, flibanserin. The unprecedented route was designed for efficient operation in flow, consisting of heterogeneously catalyzed reductive amination...

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...

Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery

09 Jun 2023 | Contributor(s): Thompson, M. R., Weatherley, S., Pukadyil, R. N., Sheskey, P. J.

This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work...

Forbidden Chemistries - Paths to a Sustainable Future Engaging Continuous Processing

09 Jun 2023 | Contributor(s): Gutmann, B, Kappe, CO

Optimizing current chemical processes alone does not yield the improvements required in the fine chemical and pharmaceutical industries. At least partially, a switch from batch to continuous manufacturing is needed. Cost-, time-, and atom-efficient routes frequently demand the application of high...

Formation of Ciprofloxacin-Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes-An Investigation into Critical Process Parameters

09 Jun 2023 | Contributor(s): Karimi-Jafari, M, Ziaee, AO'Reilly, E, Croker, D, Walker, G

The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to...

Formation of organic molecular nanocrystals under soft confinement

09 Jun 2023 | Contributor(s): Yang, XC, Ong, TCMichaelis, VK, Heng, S, Griffin, RG, Myerson, AS

Methods to produce nano-sized organic molecular crystals in thin films are of great interest in the pharmaceutical industry due to the potential benefit of increased solubility of poorly soluble drugs and the advantages of film-based dosage forms over traditional tablet/capsule-based dosage...

Formulation development of a continuously manufactured orodispersible film containing warfarin sodium for individualized dosing

23 Jul 2024 | Contributor(s): Niese, Svenja, Quodbach, Julian

Continuously manufactured orodispersible films (ODFs) offer a promising approach for individualized therapy with an easy to administer solid dosage form. The aim of this study was to develop a long ODF containing warfarin sodium to enable safe and more flexible dosing. Formulation development was...

From circular synthesis to material manufacturing: advances, challenges, and future steps for using flow chemistry in novel application area

09 Jun 2023 | Contributor(s): Sivo, A, Galaverna, RDGomes, GR, Pastre, JC, Vile, G

Continuous-flow technologies are becoming increasingly relevant in the chemistry field. The vast arrays of reactor design, in terms of structural geometry, mixing, and residence time, the modularity of these systems, adaptable for every application, and the easy downstream integrations are at the...

From form to function: Crystallization of active pharmaceutical ingredients

09 Jun 2023 | Contributor(s): Variankaval, Narayan, Cote, Aaron S., Doherty, Michael F.

In this perspective, we describe the state-of-the-art in API crystal product and process design, highlight barriers that currently prevent the production of better, cheaper crystalline products, and give our best estimate of where the field is going and should go during the next decade.

From p-Xylene to Ibuprofen in Flow: Three-Step Synthesis by a Unified Sequence of Chemoselective C−H Metalations

10 May 2024 | Contributor(s): Lee, Hyune-Jea, Kim, Dong-Pyo, Kim, Heejin

Ibuprofen was prepared from an inactive and inexpensive p-xylene by three-step flow functionalizations through chemoselective metalations of benzyl positions in sequence using an in situ generated LICKOR-type superbase. The flow approach in the microreactor facilitated the comprehensive...

From powder to tablets: Investigation of residence time distributions in a continuous manufacturing process train as basis for continuous process verification

09 Jun 2023 | Contributor(s): Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus

The essence of Continuous Manufacturing (CM) resides in the fact that continuous process units are directly connected to each other forming a continuous process train. The thorough understanding of material flow in this train based on suitable sensors, including on-line process analytical...

Fully automated continuous flow synthesis of 4,5-disubstituted oxazoles

12 Oct 2023 | Peer-reviewed journal | Contributor(s): Baumann M, Baxandale. I, Ley S, Smith G, Tranmer G

A multipurpose mesofluidic flow reactor capable of producing gram quantities of material has been developed as an automated synthesis platform for the rapid on-demand synthesis of key building blocks and small exploratory libraries. The reactor is configured to provide the maximum flexibility for...

Future Supply Chains Enabled by Continuous Processing - Opportunities and Challenges

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Jagjit Singh Srai, Markus Krumme, Mauricio Futran, Clive Badman, Craig Johnston

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily “continuous processing”-based supply chain. The current predominantly “large batch” and centralized manufacturing system designed for the “blockbuster” drug has driven a slow-paced,...

Generic Framework for Crystallization Processes Using the Population Balance Model and Its Applicability

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Shaikh, Latif J., Bari, Atul H. Ranade, Vivek V., Pandit, Aniruddha B.

A generic modeling framework for batch cooling crystallization processes has been developed to understand the crystallization process from operational and modeling point of view. The generic framework for crystallization process modeling incorporates the characteristic dimensions of crystals and...

Global Regulatory Landscape

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Matsuda, Y

Continuous manufacturing (CM) of pharmaceuticals is a rapidly growing approach in the production of active pharmaceutical ingredients and finished products. The European Medicines Agency, the US Food and Drug Administration, and the Pharmaceuticals and Medical Devices Agency have independently...

Good Manufacturing Practice Guide for Active Pharmacetuical Ingredients

09 Jun 2023 | Document

Guideline highlgihts important aspects of manufacturing API.

Granulation development in batch-to-batch and continuous processes from a quality by design perspective

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ko, Seung Jin, Lee, Ju-Hyun, Kang, Chin-Yang, Park, Jun-Bom

The process of quality by design (QbD) is of great importance in drug development. This review describes the design of experiments (DoE) method, which is an important component of QbD. DoE is predominantly divided into a screening phase and an optimization phase. The screening phase uses...

Granulation of increasingly hydrophobic formulations using a twin screw granulator

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Yu, Shen, Reynolds, Gavin K., Huang, Zhenyu, de Matas, Marcel, Salman, Agba D.

The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has...