100% visual inspection of tablets produced with continuous direct compression and coating

09 Jun 2023 | Contributor(s): Barimani, Shirin, Sibanc, Rok, Tomazevic, Dejan, Meier, Robin, Kleinebudde, Peter

Visual appearance of tablets is an important property for patients. Since the visual appearance is most strongly influenced by the applied coating, this necessitates a high level of process control and homogeneity in the coating process. In recent years, a number of tablet coaters have been...

A brief review on Process Analytical Technology (PAT)

09 Jun 2023 | Contributor(s): Mali, Akash, Jagtap, Monali, Karekar, P., Maruska, A

Process analytical technology (PAT) has been defined as a mechanism to design, analyze and control pharmaceutical manufacturing processes through measurement of critical process parameters which affect critical quality attributes. PAT checks the quality of raw material attributes both physically...

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 comprehensive overview of extended release oral dosage forms manufactured through hot melt extrusion and its combination with 3D printing

09 Jun 2023 | Contributor(s): Nashed, Nour, Lam, Matthew, Nokhodchi, Ali

Oral dosage formulations are considered to be the most convenient pharmaceutical dosage forms for almost all ages because of their simplicity and non-invasive administration compared to other dosage forms. To improve therapeutic efficacy and avoid frequent daily doses, extending drug release...

A Continuous Flow Sulfuryl Chloride-Based Reaction—Synthesis of a Key Intermediate in a New Route toward Emtricitabine and Lamivudine

25 Jun 2024 | Contributor(s): Souza, Juliana M. de, Berton, Mateo, Snead, David R., McQuade, D. Tyler

We demonstrate a continuous two-step sequence in which sulfenyl chloride is formed, trapped by vinyl acetate, and chlorinated further via a Pummerer rearrangement. These reactions produce a key intermediate in our new approach to the oxathiolane core used to prepare the antiretroviral medicines...

A Continuous Flow Sulfuryl Chloride-Based Reaction—Synthesis of a Key Intermediate in a New Route toward Emtricitabine and Lamivudine

25 Jun 2024 | Contributor(s): Souza, Juliana M. de, Berton, Mateo, Snead, David R., McQuade, D. Tyler

We demonstrate a continuous two-step sequence in which sulfenyl chloride is formed, trapped by vinyl acetate, and chlorinated further via a Pummerer rearrangement. These reactions produce a key intermediate in our new approach to the oxathiolane core used to prepare the antiretroviral medicines...

A Continuous Flow Sulfuryl Chloride-Based Reaction—Synthesis of a Key Intermediate in a New Route toward Emtricitabine and Lamivudine

23 Jul 2024 | Contributor(s): Souza, Juliana M. de, Berton, Mateo, Snead, David R., McQuade, D. Tyler

We demonstrate a continuous two-step sequence in which sulfenyl chloride is formed, trapped by vinyl acetate, and chlorinated further via a Pummerer rearrangement. These reactions produce a key intermediate in our new approach to the oxathiolane core used to prepare the antiretroviral medicines...

A Continuous Flow Sulfuryl Chloride-Based Reaction—Synthesis of a Key Intermediate in a New Route toward Emtricitabine and Lamivudine

23 Jul 2024 | Contributor(s): Souza, Juliana M. de, Berton, Mateo, Snead, David R., McQuade, D. Tyler

We demonstrate a continuous two-step sequence in which sulfenyl chloride is formed, trapped by vinyl acetate, and chlorinated further via a Pummerer rearrangement. These reactions produce a key intermediate in our new approach to the oxathiolane core used to prepare the antiretroviral medicines...

A Continuous Process for Buchwald–Hartwig Amination at Micro-, Lab-, and Mesoscale Using a Novel Reactor Concept

25 Jun 2024 | Contributor(s): Falß, Sebastian, Tomaiuolo, Giovanna, Perazzo, Antonio, Hodgson, Paul, Yaseneva, Polina, Zakrzewski, Jacek, Guido, Stefano, Lapkin, Alexei, Woodward, Robert, Meadows, Rebecca E.

A continuous Buchwald–Hartwig reaction using the bulky N-heterocyclic carbene (NHC) precatalyst [Pd(IPr*)(cin)Cl] 4 has been developed for the synthesis of a key pharmaceutical intermediate 2. Using microreactor technology, the reaction could be optimized under dilute conditions with low material...

A Continuous Process for Buchwald–Hartwig Amination at Micro-, Lab-, and Mesoscale Using a Novel Reactor Concept

23 Jul 2024 | Contributor(s): Falß, Sebastian, Tomaiuolo, Giovanna, Perazzo, Antonio, Hodgson, Paul, Yaseneva, Polina, Zakrzewski, Jacek, Guido, Stefano, Lapkin, Alexei, Woodward, Robert, Meadows, Rebecca E.

A continuous Buchwald–Hartwig reaction using the bulky N-heterocyclic carbene (NHC) precatalyst [Pd(IPr*)(cin)Cl] 4 has been developed for the synthesis of a key pharmaceutical intermediate 2. Using microreactor technology, the reaction could be optimized under dilute conditions with low material...

A Flow Process Built upon a Batch Foundation—Preparation of a Key Amino Alcohol Intermediate via Multistage Continuous Synthesis

25 Jun 2024 | Contributor(s): Lim, John Jin, Arrington, Kenneth, Dunn, Anna L., Leitch, David C., Andrews, Ian, Curtis, Neil R., Hughes, Mark J., Tray, Daniel R., Wade, Charles E., Whiting, Matthew P., Goss, Charles, Liu, Yangmu Chloe, Roesch, Brian M.

This paper describes recent efforts to apply flow technology in the preparation of the key amino alcohol intermediate 3b so as to address manufacturability issues present in the batch process of a PRMT5 inhibitor. The continuous process, one of the first reported pharmaceutical processes to use...

A Flow Process Built upon a Batch Foundation—Preparation of a Key Amino Alcohol Intermediate via Multistage Continuous Synthesis

23 Jul 2024 | Contributor(s): Lim, John Jin, Arrington, Kenneth, Dunn, Anna L., Leitch, David C., Andrews, Ian, Curtis, Neil R., Hughes, Mark J., Tray, Daniel R., Wade, Charles E., Whiting, Matthew P., Goss, Charles, Liu, Yangmu Chloe, Roesch, Brian M.

This paper describes recent efforts to apply flow technology in the preparation of the key amino alcohol intermediate 3b so as to address manufacturability issues present in the batch process of a PRMT5 inhibitor. The continuous process, one of the first reported pharmaceutical processes to use...

A Focused and Flexible Analytical Strategy is Key to Unlocking the Benefits of Continuous Manufacturing

11 Apr 2024 | Website | Contributor(s): Bikash Chatterjee

Continuous manufacturing processes promise shorter manufacturing cycle times without the need for intermediate storage, sampling testing and release of intermediate process steps, and shorter product release times through the intelligent application of in-line and at-line testing strategies....

A Framework for Representative Sampling for NIR Analysis – Theory of Sampling (TOS)

09 Jun 2023 | Chapter Book | Contributor(s): Esbensen, Kim H, Ciurczak, Emil W., Igne, Benoît, Workman, Jr.,Jerome, Burns, Donald A., Romañach, Rodolfo J.

This chapter deals with all critical steps before near-infrared spectroscopy (NIR) analysis, irrespective of whether the total sampling error contribution is large, intermediate, or small – all cases can be treated identically, including the widespread sensor-based solutions from the...

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 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 modeling and control framework for extraction processes

05 Sep 2024 | Peer-reviewed journal | Contributor(s): Peter Neugebauer, Jakob Rehrl, Peter Poechlauer, Dirk Kirschneck, Martin Horn, Martin Steinberger, Stephan Sacher, Joscha Boehm, Daniel Moser

Many continuously operated pharmaceutical process routes have been presented recently. Most of these cover the synthesis of the active pharmaceutical ingredient (API) or solid dosage processing. However, the API purification is also gaining attraction. One widespread and waste-intensive unit...

A PAT-based qualification of pharmaceutical excipients produced by batch or continuous processing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Hertrampf A., Müller H., Menezes J.C., Herdling T.

Pharmaceutical excipients have an influence on the main requirements for medicinal products (viz., quality, safety and efficacy) but also on their manufacturability. During product lifecycle it may become necessary to introduce minor changes (e.g., to continuously improve it) or major changes in...

A Perspective on Quality by Design: A Preclinical Opportunity

28 Mar 2024 | Document | Contributor(s): Ajaz S. Hussain

A perspective on Quality-by-Control (QbC) in pharmaceutical continuous manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Su, Qinglin, Ganesh, Sudarshan Moreno, Mariana Bommireddy, Yasasvi, Gonzalez, Marcial, Reklaitis, Gintaras V., Nagy, Zoltan K.

The Quality-by-Design (QbD) guidance issued by the US Food and Drug Administration (FDA) has catalyzed the modernization of pharmaceutical manufacturing practices including the adoption of continuous manufacturing. Active process control was highlighted recently as a means to improve the QbD...

A review of emerging technologies enabling improved solid oral dosage form manufacturing and processing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sohail Arshad, Muhammad, Zafar, Saman, Yousef, Bushra, Alyassin, Yasmine, Ali, Radeyah, AlAsiri, Ali, Chang, Ming-Wei, Ahmad, Zeeshan, Ali Elkordy, Amal, Faheem, Ahmed, Pitt, Kendal

Tablets are the most widely utilized solid oral dosage forms because of the advantages of self-administration, stability, ease of handling, transportation, and good patient compliance. Over time, extensive advances have been made in tableting technology. This review aims to provide an insight...

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 Review of Process Analytical Technology (PAT) in the U.S. Pharmaceutical Industry

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Munson, James, Stanfield, C. Freeman, Gujral, Bir

Process Analytical Technologies (PAT) are used to provide timely analysis of critical quality parameters with the end goal of improving final product quality as well as reducing manufacturing costs, thereby significantly benefiting the Pharmaceutical Industry. PAT involves mostly on-line or...

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...