Acceleration of Anti-Markovnikov Hydroamination in the Synthesis of an Active Pharmaceutical Ingredient

09 Jun 2023 | Contributor(s): Mitic, A, Skovby, TDam-Johansen, K, Gernaey, KV

Slow chemical reactions are a big challenge in the modern pharmaceutical industry. Their accelerations together with the introduction of continuous manufacturing modes are major drivers for future development. One example reaction is hydroamination, a reaction between unsaturated hydrocarbons and...

Achieving Continuous Manufacturing for Final Dosage Formation: Challenges and How to Meet Them

09 Jun 2023 | Contributor(s): Byrn, Stephen, Futran, Maricio, Thomas, Hayden, Jayjock, Eric, Maron, Nicola, Meyer, Robert F., Myerson, Allan S., Thien, Michael P., Trout, Bernhardt L.

We describe the key issues and possibilities for continuous final dosage formation, otherwise known as downstream processing or drug product manufacturing. A distinction is made between heterogeneous processing and homogeneous processing, the latter of which is expected to add more value to...

A scaled down method for identifying the optimum range of L/S ratio in twin screw wet granulation using a regime map approach

09 Jun 2023 | Contributor(s): Pradhan, Shankali U., Bullard, Joseph W., Dale, Steven, Ojakovo, Peter, Bonnassieux, Alexandre

Twin screw wet granulation (TSWG) has gained momentum in the pharmaceutical industry for effective continuous granulation of solid dosage products. Liquid-to-solid (L/S) ratio is a key process parameter affecting granule properties. Identifying an optimum range of L/S ratio while reducing the...

A segmented flow platform for on-demand medicinal chemistry and compound synthesis in oscillating droplets

09 Jun 2023 | Contributor(s): Hwang, YJ, Coley, CWAbolhasani, M, Marzinzik, AL, Koch, G, Spanka, C, Lehmann, H, Jensen, KF

We report an automated flow chemistry platform that can efficiently perform a wide range of chemistries, including single/multi-phase and single/multi-step, with a reaction volume of just 14 mu L. The breadth of compatible chemistries is successfully demonstrated and the desired products are...

A Semi-Continuous Operations Model For Solid-Dose Manufacturing

09 Jun 2023 | Contributor(s): Pazhayattil, Ajay Babu, Sayeed-Desta, Naheed

This article will explore the evolving generic drug environment in the U.S. It will also describe an operations model for semi-continuous manufacturing of generic solid-dose products that will improve flexibility and enable just-in-time production.

A solution for low-dose feeding in continuous pharmaceutical processes

09 Jun 2023 | Contributor(s): Sacher, S, Heindl, NUrich, JAA, Kruisz, J, Khinast, JG

Continuous feeding of small quantities of powder is increasingly applied in pharmaceutical manufacturing. With that regard, what is crucial is not only the feasibility, but also the accuracy and stability. To enable stable processing, low amounts of various agents, e.g., lubricants, can be used....

A Stochastic Population Balance Equation Model for Nucleation and Growth of Crystals with Multiple Polymorphs

09 Jun 2023 | Contributor(s): Maggioni, Giovanni, Mazzotti, Marco

Understanding polymorph crystallization is important due to the different properties, such as bioavailability or crystal shape, exhibited by the different crystal forms. In this work, we present a model, based on population balance equations, describing the unseeded crystallization by cooling of...

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

09 Jun 2023 | Contributor(s): Urwin, SJ, Levilain, GMarziano, I, Merritt, JM, Houson, I, Ter;Horst, JH

The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to...

A Study on In-Line Tablet Coating-the Influence of Compaction and Coating on Tablet Dimensional Changes

09 Jun 2023 | Contributor(s): Cahyadi, C., Tan, B. X., Chan, L. W., Heng, P. W. S.

Prior to coating, tablets are usually stored for a definite period to enable complete strain recovery and prevent subsequent volumetric expansion-related coating defects. In-line coating is defined as the coating of tablets immediately after compaction. In-line coating will be expected to improve...

A systematic computer aided framework for design and analysis of PAT systems

09 Jun 2023 | Contributor(s): Gernaey, Krist, Singh, Ravendra, Gani, Rafiqul

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A Systematic Framework for Data Management and Integration in a Continuous Pharmaceutical Manufacturing Processing Line

09 Jun 2023 | Contributor(s): Cao, Huiyi, Mushnoori, Srinivas, Higgins, Barry, Kollipara, Chandrasekhar, Fermier, Adam, Hausner, Douglas, Jha, Shantenu, Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

As the pharmaceutical industry seeks more efficient methods for the production of higher value therapeutics, the associated data analysis, data visualization, and predictive modeling require dependable data origination, management, transfer, and integration. As a result, the management and...

A systematic framework for onsite design and implementation of a control system in a continuous tablet manufacturing process

09 Jun 2023 | Contributor(s): Singh, Ravendra, Sahay, Abhishek Muzzio, Fernando Ierapetritou, Marianthi, Ramachandran, Rohit

A novel manufacturing strategy based on continuous processing integrated with online/inline monitoring tools coupled with an advanced control system is highly desired for efficient Quality by Design (QbD)-based pharmaceutical manufacturing. A control system ensures the predefined end product...

A Systematic Framework for Process Control Design and Risk Analysis in Continuous Pharmaceutical Solid-Dosage Manufacturing

09 Jun 2023 | Contributor(s): Su, Qinglin, Moreno, Mariana, Giridhar, Arun, Reklaitis, Gintaras, Nagy, Zoltan

The paradigm shift in the pharmaceutical industry to continuous manufacturing, which has recently progressed from conceptual demonstration to pilot production, has stimulated the development and application of process systems engineering (PSE) tools for implementing efficient and robust control...

A Systematic Framework for the Design and Implementation of Sensing and Control Architecture for a Continuous Pharmaceutical Manufacturing Plant

09 Jun 2023 | Contributor(s): Singh, Ravendra, Muzzio, Fernando J Ierapetritou, Marianthi, Ramachnadran, Rohit

The continuous pharmaceutical manufacture (CPM) plant and control architecture developed earlier is currently being widely implemented in industries [1,2]. CPM indeed provides an appropriate platform to implement suitable monitoring and control architecture, to improve product quality, and to...

A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses

09 Jun 2023 | Contributor(s): Leys, L., Vanbillemont, B., Van Bockstal, P. J., Lammens, J., Nuytten, G., Corver, J., Vervaet, C., De Beer, T.

An innovative continuous spin-freeze-drying technology for unit doses was recently developed. For this technology, a mechanistic primary drying model was developed allowing the calculation of the optimal dynamic drying trajectory for spin-frozen formulations. In this work, a model-based and...

A Process for the Formation of Nanocrystals of Active Pharmaceutical Ingredients with Poor Aqueous Solubility in a Nanoporous Substrate

09 Jun 2023 | Contributor(s): O'Mahony, M, Leung, AKFerguson, S, Trout, BL, Myerson, AS

A potential process for the formation of nanocrystals of the poorly soluble drug, ibuprofen, within a nanoporous material is demonstrated. Nanocrystalline ibuprofen (IBP) is prepared at <= 106 nm by adding a solution containing IBP to particles of controlled pore glass (CPG) within a column so...

A quality by design approach to investigate the effect of mannitol and dicalcium phosphate qualities on roll compaction

09 Jun 2023 | Contributor(s): Souihi, Nabil, Dumarey, Melanie, Wikstrom, Hakan, Tajarobi, Pirjo, Fransson, Magnus, Svensson, Olof, Josefson, Mats, Trygg, Johan

Roll compaction is a continuous process for solid dosage form manufacturing increasingly popular within pharmaceutical industry. Although roll compaction has become an established technique for dry granulation, the influence of material properties is still not fully understood. In this study, a...

A retrofit strategy to achieve “Fast, Flexible, Future (F3)” pharmaceutical production processes

09 Jun 2023 | Contributor(s): Singh, Ravendra, Rozada-Sanchez, Raquel Wrate, Tim Muller, Frans Gernaey, Krist V Gani, Rafiqul, Woodley, John M

n the work reported here, a substrates adoption methodology for a series of similar substrates has been developed as part of a retrofit strategy. The objective is to achieve “fast, flexible and future” pharmaceutical production processes by adapting a generic modular process-plant template....

A review of emerging technologies enabling improved solid oral dosage form manufacturing and processing

09 Jun 2023 | Contributor(s): Sohail Arshad, Muhammad, Zafar, Saman, Yousef, Bushra, Alyassin, Yasmine, Ali, Radeyah, AlAsiri, Ali, Chang, Ming-Wei, Ahmad, Zeeshan, Ali Elkordy, Amal, Faheem, Ahmed, Pitt, Kendal

Tablets are the most widely utilized solid oral dosage forms because of the advantages of self-administration, stability, ease of handling, transportation, and good patient compliance. Over time, extensive advances have been made in tableting technology. This review aims to provide an insight...

A review of PAT strategies in secondary solid oral dosage manufacturing of small molecules

09 Jun 2023 | Contributor(s): Laske, Stephan, Paudel, Amrit, Scheibelhofer, Otto, Sacher, Stephan, Hoermann, Theresa, Khinast, Johannes, Kelly, Adrian, Rantannen, Jukka, Korhonen, Ossi, Stauffer, Fanny, De Leersnyder, Fien, De Beer, Thomas, Mantanus, Jerome, Chavez, Pierre-Francois, Thoorens, Benjamin, Ghiotti, Patrizia, Schubert, Martin, Tajarobi, Pirjo, Haeffler, Gunnar, Lakio, Satu, Fransson, Magnus, Sparen, Anders, Abrahmsen-Alami, Susanna, Folestad, Staffan, Funke, Adrian, Backx, Ivo, Kavsek, Barbara, Kjell, Francois, Michaelis, Marc, Page, Trevor, Palmer, John, Schaepman, Alexander, Sekulic, Sonja, Hammond, Steve, Braun, Birgit, Colegrove, Brenda

Pharmaceutical solid oral dosage product manufacturing is a well-established, yet revolutionizing area. To this end, process analytical technology (PAT) involves interdisciplinary and multivariate (chemical, physical, microbiological and mathematical) methods for material (e.g. materials,...

A Review of Process Analytical Technology (PAT) in the U.S. Pharmaceutical Industry

09 Jun 2023 | Contributor(s): Munson, James, Stanfield, C. Freeman, Gujral, Bir

Process Analytical Technologies (PAT) are used to provide timely analysis of critical quality parameters with the end goal of improving final product quality as well as reducing manufacturing costs, thereby significantly benefiting the Pharmaceutical Industry. PAT involves mostly on-line or...

A review of twin screw wet granulation mechanisms in relation to granule attributes

09 Jun 2023 | Contributor(s): Zhang, Yi, Liu, Tongzhou, Kashani-Rahimi, Shahab, Zhang, Feng

Due to the trend of continuous pharmaceutical manufacturing, twin screw wet granulation (TSWG), a continuous process, has gained increased Research Article interest as a potential substitution of traditional batch granulation processes. Despite the complex nature of TSWG, its mechanisms have been...

A review on the taste masking of bitter APIs: hot-melt extrusion (HME) evaluation

09 Jun 2023 | Contributor(s): Maniruzzaman, M, Boateng, JSChowdhry, BZ, Snowden, MJ, Douroumis, D

The majority of active pharmaceutical ingredients (APIs) found in oral dosage forms have a bitter taste. Masking the unpleasant taste of bitter, APIs is a major challenge in the development of such oral dosage forms. Taste assessment is an important quality-control parameter for evaluating...

A sampling system for flowing powders based on the theory of sampling

09 Jun 2023 | Contributor(s): Alvarado-Hernández, Bárbara B, Sierra-Vega, Nobel O, Martínez-Cartagena, Pedro, Hormaza, Manuel, Méndez, Rafael, Romañach, Rodolfo J.

An innovative chute and stream sampler system for flowing powders has been developed and tested. The system is designed for representative sampling based on the principles of the Theory of Sampling (TOS). The sampling system was used in combination with near infrared (NIR) spectroscopy to...

A New Software Framework for Implementing Crystal Growth Models to Materials of Any Crystallographic Complexity

09 Jun 2023 | Contributor(s): Zhao, Yongsheng, Tilbury, Carl J. Landis, Steven Sun, Yuanyuan, Li, Jinjin, Zhu, Peng, Doherty, Michael F.

To continue the realization of new therapeutics, a more diverse range of solid forms is being considered. Synthetic modalities are broadening beyond simple organic molecules to more complicated structures, including organic salts, cocrystals, and solvates. As in all crystalline applications,...