Critical review on the role of excipient properties in pharmaceutical powder-to-tablet continuous manufacturing

13 Aug 2024 | Peer-reviewed journal | Contributor(s): Sara Fathollahi, Pauline H. M. Janssen, Bastiaan H. J. Dickhoff, Henderik W. Frijlink

The pharmaceutical industry is gradually changing batch-wise manufacturing processes to continuous manufacturing processes, due to the advantages it has to offer. The final product quality and process efficiency of continuous manufacturing processes is among others impacted by the properties of...

Process intensification of pharmaceutical powder blending at commercial throughputs by utilizing semi-continuous mini-blending

13 Aug 2024 | Peer-reviewed journal | Contributor(s): Maarten Jaspers, Florian Tegel, Timo P. Roelofs, Fabian Starsich, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff

Process intensification involves the miniaturization of equipment while retaining process throughput and performance. The pharmaceutical industry can benefit from this approach especially during drug product development, where the availability of active pharmaceutical ingredients (API) is often...

Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Engisch, William, Muzzio, Fernando

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing,...

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Baumann, M, Baxendale, IR

The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient...

The Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): McAuliffe M.A.P., Omahony G.E., Blackshields C.A., Collins J.A., Egan D.P., Kiernan L., Oneill E., Lenihan S., Walker G.M., Crean A.M.

Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to...

Small-Volume Continuous Manufacturing of Merestinib. Part 1. Process Development and Demonstration

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Cole, KP, Reizman, BJHess, M, Groh, JM, Laurila, ME, Cope, RF, Campbell, BM, Forst, MB, Burt, JL, Maloney, TD, Johnson, MD, Mitchell, D, Polster, CS, Mitra, AW, Boukerche, M, Conder, EW, Braden, TM, Miller, RD, Heller, MR, Phillips, JL, Howell, JR

Development of a small volume continuous process that used a combination of batch and flow unit operations to manufacture the small molecule oncolytic candidate merestinib is described. Continuous processing was enabled following the identification and development of suitable chemical...

Small-Volume Continuous Manufacturing of Merestinib. Part 2.Technology Transfer and cGMP Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Reizman, Brandon J., Hess, Molly, Burt, Justin L., Maloney, Todd D., Johnson, Martin D., Laurila, Michael E., Cope, Richard F., Luciani, Carla V., Buser, Jonas Y., Campbell, Bradley M., Forst, Mindy B., Mitchell, David, Braden, Timothy M., Lippelt, Christopher K., Boukerche, Moussa, Starkey, Derek R., Miller, Richard D., Chen, Jing, Sun, Baoquan, Kwok, Martin, Zhang, Xin, Tadayon, Sam, Huang, Ping

Technology transfer of a small volume continuous (SVC) process and Current Good Manufacturing Practices (cGMP) manufacturing of merestinib are described. A hybrid batch-SVC campaign was completed at a contract manufacturing organization under cGMP. The decision process by which unit operations...

Simulation-Based Design of an Efficient Control System for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, M, Singh, R, Ramachandran, R

In this study, an efficient system-wide controlsystem has been designed for the integrated continuous purification and processing of the active pharmaceutical ingredient (API). The control strategy is based on the regulatory PID controller which is most widely used in the manufacturing industry...

Real-Time Monitoring of Powder Mass Flowrates for Plant-Wide Control of a Continuous Direct Compaction Tablet Manufacturing Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Huang, Yan-Shu, Medina-González, Sergio Straiton, Benjamin Keller, Joshua, Marashdeh, Qussai, Gonzalez, Marcial, Nagy, Zoltan, Reklaitis, Gintaras V.

While measurement and monitoring of powder/particulate mass flow rate are not essential to the execution of traditional batch pharmaceutical tablet manufacturing, in continuous operation, it is an important additional critical process parameter. It has a key role both in establishing that the...

Process optimization for continuous extrusion wet granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Tan, L, Carella, AJ, Ren, YK, Lo, JB

Three granulating binders in high drug-load acetaminophen blends were evaluated using high shear granulation and extrusion granulation. A polymethacrylate binder enhanced tablet tensile strength with rapid disintegration in simulated gastric fluid, whereas polyvinylpyrrolidone and hydroxypropyl...

Process dynamics and control of API manufacturing and purification processes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, Maitraye, Singh, Ravendra, Ramachandran, Rohit

The pharmaceutical industries have started transitioning toward continuous mode of manufacturing recently. Due to many advantages of the continuous manufacturing over the traditional alternatives, the industries are putting huge effort to efficiently adapt the continuous processing mode. However,...

Process design applied to optimise a directly compressible powder produced via a continuous manufacturing process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Gonnissen, Y., Goncalves, S. I. V., De Geest, B. G., Remon, J. P., Vervaet, C.

Manufacturing of 'ready-to-compress' powder mixtures for direct compression was performed by spray drying, without granulation, milling and/or blending steps in between spray drying and compaction. Powder mixtures containing acetaminophen, mannitol, erythritol, maltodextrin, crospovidone,...

Pharmaceutical Crystallization

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Chen, J, Sarma, BEvans, JMB, Myerson, AS

Crystallization is crucial in the pharmaceutical industry as a separation process for intermediates and as the final step in the manufacture of active pharmaceutical ingredients (APIs). In this perspective article to celebrate 10 years of Crystal Growth & Design, we focus on three areas related...

Multi-scale flowsheet simulation of an integrated continuous purification-downstream pharmaceutical manufacturing process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, M, Chaudhury, ASingh, R, John, J, Ramachandran, R

Properties of active pharmaceutical ingredients influence the critical quality attributes (CQAs) of final solid dosage forms (e. g. tablets). In the last decade, continuous manufacturing has been shown to be a promising alternative to batch processing in the pharmaceutical industry. Therefore, a...

Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Lee, SL, O'Connor, TFYang, XC, Cruz, CN, Chatterjee, S, Madurawe, RD, Moore, CMV, Yu, LX, Woodcock, J

Currently, there is a high level of interest in the pharmaceutical industry in continuous-manufacturing strategies, integrated with online-monitoring tools, that are designed, optimized, and controlled using advanced, model-predictive systems. These strategies can accelerate the full...

Model-Based Control-Loop Performance of a Continuous Direct Compaction Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ramachandran, Rohit, Arjunan, Jeyrathan, Chaudhury, Anwesha, Ierapetritou, Marianthi G

This study is concerned with enhanced model-based control of a continuous direct compression pharmaceutical process. The control-loop performance is assessed in silico and results obtained will be incorporated into the pilot plant facility of the continuous direct compaction process at the NSF...

Loss-in-Weight Feeding Trials Case Study: Pharmaceutical Formulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Engisch, WE, Muzzio, FJ

This article presents a case study of a continuous feeding strategy for five pharmaceutical components (active pharmaceutical ingredient (API), Prosolv HD90, crospovidone, magnesium stearate, and colloidal silicon dioxide), for the purpose of developing a direct compression continuous...

Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vercruysse, J, Burggraeve, A., Fonteyne, M., Cappuyns, P., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Vervaet, C.

Twin screw granulation (TSG) has been reported by different Research Article groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution...

Implementation of an advanced hybrid MPC–PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plan

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Sahay, Abhishek, Karry, Krizia, Muzzio, Fernando, Ierapetritou, Marianthi, Ramachandran, Rohit

It is desirable for a pharmaceutical final dosage form to be manufactured through a quality by design (QbD)-based approach rather than a quality by testing (QbT) approach. An automatic feedback control system coupled with PAT tools that is part of the QbD paradigm shift, has the potential to...

Implementation of control system into continuous pharmaceutical manufacturing pilot plant (powder to tablet)

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra

Real-time process control is highly desired for efficient quality by design (QbD)-based pharmaceutical manufacturing. A control system ensures the predefined end-product quality, satisfies the high regulatory constraints, facilitates real-time release of the product, and optimizes the resources....

Hybrid advanced control of flexible multipurpose continuous tablet manufacturing process via direct compaction

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

With numerous case studies throughout, this valuable guide is ideal for those engaged in, or learning about, continuous processing in pharmaceutical manufacturing.

Forbidden Chemistries - Paths to a Sustainable Future Engaging Continuous Processing

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

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...

Development of drying-induced stresses in pharmaceutical granules prepared in continuous production line

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Mezhericher, Maksim

The phenomenon of development of drying-induced stresses has been given a through consideration in the literature on drying of many products. At the same time, to the best of our knowledge, the open published sources contain no information on drying stresses in pharmaceutical granules prepared by...

Development and implementation of an advanced model predictive control system into continuous pharmaceutical tablet compaction process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bhaskar, Aparajith, Barros, Fernando N, Singh, Ravendra

In the context of continuous pharmaceutical oral dosage manufacturing, a control system is essential to ensure that the critical quality attributes (CQAs) are maintained within the regulatory constraints by mitigating variations generated in upstream operations. Such a system is essential to the...