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

09 Jun 2023 | 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 | 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 | 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...

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

09 Jun 2023 | 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...

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

09 Jun 2023 | 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 | 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 | 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...

Cellulose Ethers for Extrusion Applications

09 Jun 2023 | 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 | 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...

Assessing inter- and intramolecular continuous-flow strategies towards methylphenidate (Ritalin) hydrochloride

09 Jun 2023 | Contributor(s): Gerardy, R, Winter, MVizza, A, Monbaliu, JCM

The batch-to-flow translation of inter-and intramolecular strategies for the diastereoselective preparation of the active pharmaceutical ingredient threo-methylphenidate hydrochloride is presented. Both inter-and intramolecular strategies imply the telescoping of multiple processing steps and the...

Assessing the Greenness of Mechanochemical Processes with the DOZN 2.0 Tool br

09 Jun 2023 | Contributor(s): Sharma, P, Vetter, CPonnusamy, E, Colacino, E

As the demand increases for more sustainable chemical production,mechanochemical processes have been proposed as greener alternatives to traditional manufacturing methods. To support the transition to mechanochemical processes,quantitative assessment methods must be developed to measure and...

Assessment and prediction of tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy

09 Jun 2023 | Contributor(s): Peeters, Elisabeth, Tavares da Silva, Ana Filipa, Toiviainen, Maunu, Van Renterghem, Jeroen, Vercruysse, Jurgen, Juuti, Mikko, Lopes, Joao Almeida, De Beer, Thomas., Vervaet, Chris, Remon, Jean-Paul

This study investigated whether Raman and Near Infrared (NIR) spectroscopy could predict tablet properties. Granules were produced on a continuous line by varying granulation parameters. Tableting process parameters were adjusted to obtain uniform tablet weight and thickness. Spectra were...

Assessment of blend uniformity in a continuous tablet manufacturing process

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel, Román-Ospino, Andrés, Scicolone, James, Muzzio, Fernando, Romañach, Rodolfo, Mendez, Rafael

Blend uniformity was monitored throughout a continuous manufacturing (CM) process by near infrared (NIR) spectroscopic measurements of flowing blends and compared to the drug concentration in the tablets. The NIR spectra were obtained through the chute after the blender and within the feed frame,...

Assessment of blending performance of pharmaceutical powder mixtures in a continuous mixer using Discrete Element Method (DEM)

09 Jun 2023 | Contributor(s): Behjani, MA, Motlagh, YGBayly, AE, Hassanpour, A

This study proposes a new sample-independent mixing index, termed the Coefficient of Blending Performance (CBP), for monitoring the formation of undesired API (Active Pharmaceutical Ingredient) agglomerates in continuous mixing processes. The proposed index is examined for the blending of...

Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review

09 Jun 2023 | Contributor(s): Simon, Levente L, Pataki, Hajnalka, Marosi, György, Meemken, Fabian, Hungerbühler, Konrad, Baiker, Alfons, Tummala, Srinivas, Glennon, Brian, Kuentz, Martin, Steele, Gerry, Kramer, Herman J. M, Rydzak, James W.

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in...

Assessment of Robustness for a Near-Infrared Concentration Model for Real-Time Release Testing in a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Colon, Yleana, Vargas, Jenny, Sánchez, Eric, Navarro, Gilfredo, Romañach, Rodolfo

This study describes the robustness test of a transmission near-infrared spectroscopic (NIRS) model for prediction of drug concentration in core tablets as part of real-time release testing (RTRt) efforts for a continuous manufacturing process. Seven calibration blend samples were prepared...

Assessment of spatial heterogeneity in continuous twin screw wet granulation process using three-compartmental population balance model

09 Jun 2023 | Contributor(s): Liu, Huolong, Galbraith, Shaun C., Park, Seo-Young, Cha, Bumjoon, Huang, Zhuangrong, Meyer, Robert Frederick, Flamm, Matthew H., O'Connor, Thomas, Lee, Sau, Yoon, Seongkyu

In this study, a novel three-compartmental population balance model (PBM) for a continuous twin screw wet granulation process is developed, combining the techniques of PBM and regression process modeling. The developed model links screw configuration, screw speed, and blend throughput with...

Asymmetric distribution in twin screw granulation

09 Jun 2023 | Contributor(s): Seem, Tim Chan, Rowson, Neil A., Gabbott, Ian, de Matas, Marcel, Reynolds, Gavin K., Ingram, Andy

Positron Emission Particle Tracking (PEPT) was successfully employed to validate measured transverse asymmetry in material distribution in the conveying zones of a Twin Screw Granulator (TSG). Flow asymmetry was established to be a property of the granulator geometry and dependent on fill level....

At-line monitoring of salification process of the antiretroviral lamivudine-saccharinate salt using FT-MIR spectroscopy with multivariate curve resolution

09 Jun 2023 | Contributor(s): Mazivila, SJ, Castro, RAELeitao, JMM, da;Silva, JCGE

This article presents a promising application of Fourier transform-mid infrared (FT-MIR) spectroscopy with multivariate curve resolution - alternating least-squares (MCR-ALS) as an at-line process analytical technology (PAT) to enhancing the understanding and continuous control of a...

Application of Near-Infrared Spectroscopy in Real-Time Monitoring of Product Attributes of Ribbed Roller Compacted Flakes

09 Jun 2023 | Contributor(s): Samanta, Asim Kumar, Karande, Atul D., Ng, Ka Yun, Heng, Paul Wan Sia

This study assessed the utility of near-infrared (NIR) spectroscopy for the real-time monitoring of content uniformity and critical quality attributes (tensile strength, Young's modulus, and relative density) of ribbed roller compacted flakes made by axially corrugated or ribbed rolls. A...

Application of process analytical technology-based feedback control for the crystallization of pharmaceuticals in porous media

09 Jun 2023 | Contributor(s): Acevedo, David A., Ling, Jing Chadwick, Keith, Nagy, Zoltak K. ;

The purpose of this work is to implement a feedback control approach during the cooling crystallization of paracetamol (PCM) in porous media to increase the amount of PCM in the alginate beads (i.e., drug loading) and minimize the heterogeneous nucleation occurring in the bulk system. Two types...

Application of the quantitative detection of a change in concentration of magnesium stearate in a feeder tube of tableting manufacture by real-time near-infrared spectroscopy

09 Jun 2023 | Contributor(s): Sasakura, D., Nakayama, K., Chikuma, T.

Process analytical technology is important for the analysis and control of manufacturing processes. Near-infrared spectroscopy is widely used in various process analytical technologies for the analysis of the chemical components of solid dosage forms. Lubrication is an important process carried...

Application of Ultra-Performance Liquid Chromatography as an Online Process Analytical Technology Tool in Pharmaceutical Crystallization

09 Jun 2023 | Contributor(s): Yang, Yang, Zhang, Chuntao Pal, Kanjakha Koswara, Andy, Quon, Justin, Mckeown, Rahn, Goss, Charles, Nagy, Zoltan K

Concentration is often an important process parameter in pharmaceutical crystallization processes. In this work, an ultra-performance liquid chromatography (UPLC) system designed for process monitoring (Waters PATROL UPLC) was applied online as a process analytical technology tool for real-time...

Application of X-Ray Sensors for In-line and Noninvasive Monitoring of Mass Flow Rate in Continuous Tablet Manufacturing

09 Jun 2023 | Contributor(s): Ganesh, Sudarshan, Troscinski, Rachel, Schmall, Nicholas, Nagy, Zoltan, Reklaitis, Gintaras

The progress in continuous downstream manufacturing of oral solid doses demands effective real-time process management, with monitoring at its core. This study evaluates the feasibility of using a commercial sensor to measure the mass flow rate of the particulates, a critical process variable in...

Applications of Flow Chemistry in the Pharmaceutical Industry-Highlights of the Recent Patent Literature

09 Jun 2023 | Contributor(s): Hughes, DL

Flow chemistry is playing an increasingly important role in drug discovery, chemical process development, and manufacturing in the pharmaceutical and agrichemical industries. The current review covers patents and patent applications from 2017 to 1Q 2020 for which no accompanying journal articles...