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...

Applications of Supercritical Anti-Solvent Process in Preparation of Solid Multicomponent Systems

09 Jun 2023 | Contributor(s): Liu, GJ, Li, JJ, Deng, SM

Solid multicomponent systems (SMS) are gaining an increasingly important role in the pharmaceutical industry, to improve the physicochemical properties of active pharmaceutical ingredients (APIs). In recent years, various processes have been employed for SMS manufacturing. Control of the particle...

Approach to establishment of control strategy for oral solid dosage forms using continuous manufacturing

09 Jun 2023 | Contributor(s): Ishimoto, Hayato, Kano, Manabu, Sugiyama, Hirokazu, Takeuchi, Hirofumi, Terada, Katsuhide, Aoyama, Atsushi, Shoda, Takuji, Demizu, Yosuke, Shimamura, Jinen, Yokoyama, Reiji, Miyamoto, Yuji, Hasegawa, Koji, Serizawa, Masaru, Unosawa, Kazuomi, Osaki, Kazuo, Asai, Naochika, Matsuda, Yoshihiro

As a result of the Research Article activities of the Japan Agency for Medical Research Article and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology...

Evaluation of three approaches for real-time monitoring of roller compaction with near-infrared spectroscopy

09 Jun 2023 | Contributor(s): Acevedo, D., Muliadi, A., Giridhar, A., Litster, J. D., Romañach, R. J.

Three different approaches have been evaluated for monitoring ribbon density through real-time near-infrared spectroscopy measurements. The roll compactor was operated to produce microcrystalline cellulose (MCC) ribbons of varying densities. The first approach used the slope of the spectra which...

Artificial Intelligence Tools for Scaling Up of High Shear Wet Granulation Process

09 Jun 2023 | Contributor(s): Landin, Mariana

The results presented in this article demonstrate the potential of artificial intelligence tools for predicting the endpoint of the granulation process in high-speed mixer granulators of different scales from 25L to 600L. The combination of neurofuzzy logic and gene expression programing...

Artificial neural network modelling of continuous wet granulation using a twin-screw extruder

09 Jun 2023 | Contributor(s): Shirazian, Saeed, Kuhs, Manuel, Darwish, Shaza, Croker, Denise., Walker, Gavin M

Computational modelling of twin-screw granulation was conducted by using an artificial neural network (ANN) approach. Various ANN configurations were considered with changing hidden layers, nodes and activation functions to determine the optimum model for the prediction of the process. The neural...

Anti-fouling control of plug-flow crystallization via heating and cooling cycle

09 Jun 2023 | Contributor(s): Koswara, Andy, Nagy, Zoltan K.

Plug-flow crystallization (PFC) is a promising continuous pharmaceutical crystallization process but is prone to fouling due to uncontrolled crystallization on the reactor surface (encrustation). This results in operational issues such as (1) flow blockage, (2) increased thermal resistance, and...

API Continuous Cooling and Antisolvent Crystallization for Kinetic Impurity Rejection in cGMP Manufacturing

09 Jun 2023 | Contributor(s): Johnson, MD, Burcham, CLMay, SA, Calvin, JR, Groh, JM, Myers, SS, Webster, LP, Roberts, JC, Reddy, VR, Luciani, CV, Corrigan, AP, Spencer, RD, Moylan, R, Boyse, R, Murphy, JD, Stout, JR

Crystallization of 204 kg of final active pharmaceutical ingredient was accomplished continuously using a cascade of mixed suspension mixed product removal crystallizers in cGMP manufacturing. This article describes the journey taken to transform a set of technical to final batch crystallizations...