Batch vs. continuous direct compression – a comparison of material processability and final tablet quality

03 Jan 2024 | Peer-reviewed journal | Contributor(s): S. Fathollahi, D. Vanderroost, T. Roelofs, B.H.J. Dickhoff, C. Vervaet, V. Vanhoorne, B. Bekaert, P.H.M. Janssen

In this study, an in-depth comparison was made between batch and continuous direct compression using similar compression set-ups. The overall material processability and final tablet quality were compared and evaluated. Correlations between material properties, process parameters and final...

Batch–flow hybrid synthesis of the antipsychotic clozapine

10 May 2024 | Peer-reviewed journal | Contributor(s): Neyt, N.C., Riley, D.L.

The development of batch–flow hybrid processes is becoming an attractive prospect through which chemists can make use of the best aspects of both technologies. We have reported the implementation of an on-the-fly purification by trituration which can also be utilised to perform solvent swaps. We...

Benchtop NIR method development for continuous manufacturing scale to enable efficient PAT application for solid oral dosage form

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Alam, MA, Liu, YADolph, S, Pawliczek, M, Peeters, E, Palm, A

A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to...

Biocatalytic Continuous Manufacturing of Diabetes Drug: Plantwide Process Modeling, Optimization, and Environmental and Economic Analysis

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ho, CH, Yi, JR, Wang, XN

This work proposes a comprehensive framework of biocatalytic continuous manufacturing of sitagliptin, the active pharmaceutical ingredient of the leading dipeptidyl peptidase-4 inhibitor antidiabetic drug. Continuous manufacturing has the advantages of quality consistency, reduced waste...

Biocompatible Alginate Microgel Particles as Heteronucleants and Encapsulating Vehicles for Hydrophilic and Hydrophobic Drugs

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Eral, HB, Lopez-Mejias, VO'Mahony, M, Trout, BL, Myerson, AS, Doyle, PS

Biocompatible materials that can control crystallization while carrying large amounts of active pharmaceutical ingredients (APIs) with diverse chemical properties are in demand in industrial practice. In this study, we investigate the utility of biocompatible alginate (ALG) hydrogels as a...

Biotransformation with whole microbial systems in a continuous flow reactor: resolution of (RS)-flurbiprofen using Aspergillus oryzae by direct esterification with ethanol in organic solvent

24 Apr 2024 | Peer-reviewed journal | Contributor(s): Tamborini, Lucia, Romano, Diego, Pinto, Andrea, Contente, Martina, Iannuzzi, Maria C., Conti, Paola, Molinari, Francesco

Cell-bound lipases of dry mycelium of Aspergillus oryzae were used in organic solvent for the resolution of racemic flurbiprofen by direct esterification with ethanol in a flow-chemistry reactor. Under flow conditions a significant reduction of the reaction time and an increase of the...

Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity-A Review

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Jakubowska, E, Ciepluch, N

Content uniformity (CU) of the active pharmaceutical ingredient is a critical quality attribute of tablets as a dosage form, ensuring reproducible drug potency. Failure to meet the accepted uniformity in the final product may be caused either by suboptimal mixing and insufficient initial blend...

Blend uniformity monitoring in a continuous manufacturing mixing process for a low-dosage formulation using a stream sampler and near infrared spectroscopy

19 Jul 2024 | Peer-reviewed journal | Contributor(s): Rodolfo Romanach, Raúl S. Rangel-Gil, Juan M. Nasrala-Álvarez, Rafael Méndez

Continuous manufacturing has the potential to offer several benefits for the production of oral solid dosage forms, including reduced costs, low-scale equipment, and the application of process analytical technology (PAT) for real-time process control. This study focuses on the implementation of...

Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer

09 Jun 2023 | Peer-reviewed journal | Contributor(s): De Leersnyder, F., Vanhoorne, V., Bekaert, H., Vercruysse, J., Ghijs, M., Bostijn, N., Verstraeten, M., Cappuyns, P., Van Assche, I., Vander Heyden, Y., Ziemons, E., Remon, J. P., Nopens, I., Vervaet, C., De Beer, T.

Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and,...

Breaking Through Barriers to Continuous Manufacturing

09 Jun 2023 | Magazine | Contributor(s): Markarian, Jennifer

Pharmaceutical manufacturing is inching towards implementing more efficient and sustainable processes, including continuous manufacturing (CM) of solid-dosage drugs. Advantages of CM include the potential for faster development, easier technical transfer, and more efficient and flexible...

Catalytic hydrogenation of N-4-nitrophenyl nicotinamide in a micro-packed bed reactor

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Yang, CX, Teixeira, ARShi, YX, Born, SC, Lin, HK, Song, YFL, Martin, B, Schenkel, B, Lachegurabi, MP, Jensen, KF

Recent advancements in micro-flow technologies and a drive toward more efficient, greener and safer processes have led to a renaissance in flow-chemistry for pharmaceutical production. In this work, we demonstrate the use of a stabilized Pd nanoparticle-organic-silica catalyst to selectively...

Catalytic Static Mixers for the Continuous Flow Hydrogenation of a Key Intermediate of Linezolid (Zyvox)

25 Jun 2024 | Peer-reviewed journal | Contributor(s): Gardiner, James, Nguyen, Xuan, Genet, Charlotte, Horne, Mike D., Hornung, Christian H., Tsanaktsidis, John

Catalytic static mixers (CSMs) were used for the efficient preparation of a key intermediate of the antimicrobial drug linezolid (Zyvox). The approach combines 3D printing and additive manufacturing techniques with continuous flow processing to produce a general method for catalytic...

CDER's Emerging Technology Program

20 Nov 2023 | Workshop | Contributor(s): Thomas O’Connor

Emerging Technology Program (ETP) OverviewETP TrendsLifecycle of an Emerging TechnologyInteracting with the ETPPharmaceutical Quality Symposium 2023: Quality, Supply Chain & Advanced Manufacturing - 10/31/2023 | FDA

Cellulose Ethers for Extrusion Applications

09 Jun 2023 | Chapter Book | Contributor(s): Pinto, Elanor, Duerig, Thomas

Cellulose ethers have been used for years in developing oral dosage forms via batch processes such as direct compression and wet granulation. Recent advances in continuous manufacturing have brought about innovative technologies such as hot melt extrusion, melt extrusion granulation, and...

Challenges and Opportunities in Pharmaceutical Manufacturing Modeling and Optimization

09 Jun 2023 | Chapter Book | Contributor(s): Rogers, Amanda, Ierapetritou, Marianthi Eden, Mario R. Siirola, John D., Towler, Gavin P.

The pharmaceutical industry currently faces economic and regulatory challenges associated with process development. Process systems engineering (PSE) tools can play a role in developing robust and economically efficient manufacturing processes. However pharmaceutical companies have lagged behind...

Challenges in tracing material flow passing a loss-in-weight feeder in continuous manufacturing processes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Peterwitz, Moritz, Gerling, Sina, Schembecker, Gerhard

Loss-in-weight feeders are an integral part of most continuous manufacturing processes, ensuring a constant mass flow. The feeders cause a significant degree of back-mixing in such lines. Understanding back-mixing is essential for the treatment of disturbances. However, feeders refilled...

Challenges, opportunities and recent advances in near infrared spectroscopy applications for monitoring blend uniformity in the continuous manufacturing of solid oral dosage forms

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Velez, Natasha L., Drennen, James K., Anderson, Carl A.

Near infrared (NIR) spectroscopy has been widely recognized as a powerful PAT tool for monitoring blend uniformity in continuous manufacturing (CM) processes. However, the dynamic nature of the powder stream and the fast rate at which it moves, compared to batch processes, introduces challenges...

Characteristics of multi-component formulation granules formed using distributive mixing elements in twin screw granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Pradhan, Shankali U., Sen, Maitraye, Li, Jiayu, Gabbott, Ian, Reynolds, Gavin, Litster, James D., Wassgren, Carl R.

This work examines the influence of pharmaceutical powder formulation characteristics on granule properties formed using distributive mixing elements (DMEs) in twin screw granulation. High and low drug dose formulations with three different active pharmaceutical ingredients (APIs) were...

Characteristics of residence time distribution in a continuous high shear mixer granulation using scraper rotation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Tomita, Yosuke, Takeuchi, Yoshiko, Natsuyama, Susumu, Takeuchi, Hirofumi

Characteristics of residence time distribution (RTD) in a continuous high shear mixer granulation were investigated to promote the development of a continuous manufacturing process in the pharmaceutical industry. A continuous granulator with an impeller and a scraper was utilized. The tracer...

Characterization and Modeling of the Operating Curves of Membrane Microseparators

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Yang, L, Weeranoppanant, N, Jensen, KF

The membrane microseparator is a milliliter-scale flow chemistry module that continuously separates a biphasic flow through a PTFE microporous membrane. It has found a wide range of applications in the continuous manufacturing of active pharmaceutical ingredients and fine chemicals, especially...

Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid-Liquid Separation of Suspensions

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Steenweg, C, Seifert, AISchembecker, G, Wohlgemuth, K

A key enabler for the future success of continuous manufacturing in pharmaceutical and fine chemical production processes is the control of product quality. Since approx. 90% of all small molecular active pharmaceutical ingredients produced involve a crystallization step, a holistic view on its...

Characterization of a novel hydroxypropyl methylcellulose (HPMC) direct compression grade excipient for pharmaceutical tablets

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Allenspach, Carl, Timmins, Peter, Sharif, Shasad, Minko, Tamara

Controlled release tablets are important dosage forms enabling a slower release of the drug and better pharmacokinetics for some drugs and hydrophilic matrix tablets utilizing hydroxypropyl methylcellulose (HPMC) are one of the most common types. One of the main challenges with using HPMC is its...

Characterization of Amorphous Solid Dispersion of Pharmaceutical Compound with pH-Dependent Solubility Prepared by Continuous-Spray Granulator

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Tanaka, R, Hattori, YHorie, Y, Kamada, H, Nagato, T, Otsuka, M

A continuous-spray granulator (CTS-SGR) is a one-step granulation technology capable of using solutions or suspensions. The present Research Article objectives were, (1) to reduce the manufacturing operations for solid dosage formulations, (2) to make amorphous solid dispersion (ASD) granules...