High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

09 Jun 2023 | Contributor(s): Yu, E, Mangunuru, HPRTelang, NS, Kong, CJ, Verghese, J, Gilliland, SE, Ahmad, S, Dominey, RN, Gupton, BF

Numerous synthetic methods for the continuous preparation of fine chemicals and active pharmaceutical ingredients (API's) have been reported in recent years resulting in a dramatic improvement in process efficiencies. Herein we report a highly efficient continuous synthesis of the antimalarial...

Holistic Control Strategies for Continuous Manufacturing

09 Jun 2023 | Contributor(s): Moore, Christine, Garcia, Thomas, Hausner, Douglas B., Ben-Anat, Inna

Innovative technologies such as continuous manufacturing (CM) bring speed, efficiency, and agility to pharmaceutical manufacturing together with enhanced process robustness and assurance of product quality. During CM, material is simultaneously charged and discharged into process unit operations....

Granulation of increasingly hydrophobic formulations using a twin screw granulator

09 Jun 2023 | 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...

Grey-Box Approach for the Prediction of Variable Residence Time Distribution in Continuous Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Elkhashap, A, Meier, R, Stenger, D, Abel, D

Axial dispersion models are used for the prediction of residence time distribution (RTD) of the flow occurring in various processes. Such models are essential for the understanding of the flow dynamics allowing monitoring, control and material tracing specially in the scope of continuous...

Heat Transfer Evaluation During Twin-Screw Wet Granulation in View of Detailed Process Understanding

09 Jun 2023 | Contributor(s): Stauffer, Fanny, Ryckaert, Alexander, Van Hauwermeiren, Daan, Funke, Adrian, Djuric, Dejan, Nopens, Ingmar, De Beer, Thomas

During the last decade, the pharmaceutical industry has shown a growing interest in continuous twin-screw granulation (TSG). Despite flourishing literature on TSG, limited studies focused on fundamental process understanding on its mechanisms. In current study, granule quality attributes along...

Hot melt extrusion technology for continuous manufacturing

09 Jun 2023 | Contributor(s): Furqan Tahir, Lovett. David

Hot melt extrusion (HME), a manufacturing technique traditionally used in the plastic and food industries, is now attracting significant interest from the pharmaceutical manufacturing sector. This is primarily because HME enables the continuous manufacture of a wide variety of dosage...

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

09 Jun 2023 | Contributor(s): Patil, H, Tiwari, RV, Repka, MA

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently...

How to Design and Implement Powder-to-Tablet Continuous Manufacturing Systems

09 Jun 2023 | Contributor(s): Sarang Oka, Muzzio, Fernando

How to Design and Implement Powder-to-Tablet Continuous Manufacturing Systems provides a comprehensive overview on the considerations necessary for the design of continuous pharmaceutical manufacturing processes. The book covers both the theory and design of continuous processing of associated...

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

09 Jun 2023 | Contributor(s): Patil, H, Tiwari, RV, Repka, MA

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently...

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...

Global Regulatory Landscape

09 Jun 2023 | 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...

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...

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...

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...

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

09 Jun 2023 | 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...

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...

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...

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

09 Jun 2023 | 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...

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...

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 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...