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 Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696

25 Jun 2024 | Contributor(s): Gu, Xingxian, Zhao, Jibin, Chen, Like, Li, Yunzhong, Yu, Bo, Tian, Xiangguang, Min, Zhongcheng, Xu, Su, Gu, Huijuan, Sun, Junjie, Lu, Xiaoquan, Chang, Meng, Wang, Xufan, Zhao, Liqun, Ye, Shengqing, Yang, Hongwei, Tian, Yingtao, Gao, Feng, Gai, Yu, Jia, Guanghua, Wu, Jingjing, Wang, Yan, Zhang, Jianghua, Zhang, Xuesong, Liu, Weichun, Gu, Xin, Luo, Xi, Dong, Hai, Wang, Huaimin, Schenkel, Berthold, Venturoni, Francesco, Filipponi, Paolo, Guelat, Bertrand, Allmendinger, Thomas, Wietfeld, Bernhard, Hoehn, Pascale, Kovacic, Nikola, Hermann, Luca, Schlama, Thierry, Ruch, Thomas, Derrien, Nadine, Piechon, Philippe, Kleinbeck, Florian

LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial...

Application of Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696

23 Jul 2024 | Contributor(s): Gu, Xingxian, Zhao, Jibin, Chen, Like, Li, Yunzhong, Yu, Bo, Tian, Xiangguang, Min, Zhongcheng, Xu, Su, Gu, Huijuan, Sun, Junjie, Lu, Xiaoquan, Chang, Meng, Wang, Xufan, Zhao, Liqun, Ye, Shengqing, Yang, Hongwei, Tian, Yingtao, Gao, Feng, Gai, Yu, Jia, Guanghua, Wu, Jingjing, Wang, Yan, Zhang, Jianghua, Zhang, Xuesong, Liu, Weichun, Gu, Xin, Luo, Xi, Dong, Hai, Wang, Huaimin, Schenkel, Berthold, Venturoni, Francesco, Filipponi, Paolo, Guelat, Bertrand, Allmendinger, Thomas, Wietfeld, Bernhard, Hoehn, Pascale, Kovacic, Nikola, Hermann, Luca, Schlama, Thierry, Ruch, Thomas, Derrien, Nadine, Piechon, Philippe, Kleinbeck, Florian

LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial...

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...

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...

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...

Automated and continuous synthesis of drug substances

09 Jun 2023 | Contributor(s): Sacher, Stephan, Castillo, Ismael, Rehrla, Jakob, Sagmeistera, Peter, Lebl, René, Kruisza, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D, Kirschneck, Dirk, Kappea, C. Oliver, Horn, Martin

A continuous synthesis line was developed integrating different common reaction stepsnamely nitration, substitution and hydrogenation. Mesalazine as model drug substancewas produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PATstrategy was implemented to equip the full...

Automated and continuous synthesis of drug substances

24 Apr 2024 | Peer-reviewed journal | Contributor(s): Sacher, Stephan, Castillo, Ismael, Rehrl, Jakob, Sagmeister, Peter, Lebl, René, Kruisz, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D., Kirschneck, Dirk, Kappe, C. Oliver, Horn, Martin

A continuous synthesis line was developed integrating different common reaction steps namely nitration, substitution and hydrogenation. Mesalazine as model drug substance was produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PAT strategy was implemented to equip the...

Axial Chirality in the Sotorasib Drug Substance, Part 2: Leveraging a High-Temperature Thermal Racemization to Recycle the Classical Resolution Waste Stream

25 Jun 2024 | Peer-reviewed journal | Contributor(s): Beaver, Matthew G., Brown, Derek B., Campbell, Kiersten, Fang, Yuan-Qing, Ford, David D., Mardirossian, Narbe, Nagy, Kevin D., Rötheli, Andreas R., Sheeran, Jillian W., Telmesani, Reem, Parsons, Andrew T.

The development and kilogram-scale demonstration of a high-temperature continuous-flow racemization process to recycle the off-enantiomer of an atropisomeric sotorasib intermediate is described. Part 1 of this two-part series details the design and execution of a classical resolution to generate...

Bachem - Insights into Peptide Chemistry Achievements by the World's Leading Independent Manufacturer of Peptides

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Mergler, M, Loidl, GDiekmann, M, Dick, F

The Swiss fine chemicals company Bachem, pioneer and specialist in the chemical synthesis of peptides, has also become an internationally leading manufacturer of peptide active pharmaceutical ingredients (APIs). In response to increasing demands in scale and purity, Bachem's Research Article...