Introduction to the Theory and Practice of Sampling

09 Jun 2023 | Contributor(s): Esbensen, Kim H

Sampling is an important, but sometimes hidden, part of everyday life in science, technology, industry, society and commerce where decisions are made based on analytical results, which must be based on reliable samples. However, there is a very long and complex pathway from heterogeneous...

Investigating the Effect of APAP Crystals on Tablet Behavior Manufactured by Direct Compression

09 Jun 2023 | Contributor(s): Ghazi, Nastaran, Liu, Zhanjie, Bhatt, Chinmay, Kiang, San, Cuitino, Alberto

In this work, the effect of API's (Active Pharmaceutical Ingredient) shape and size on tablet characteristics is investigated for high API dose formulation manufactured by direct compression. Three different classes of APAP (acetaminophen) are selected, and tablets are produced in both single and...

Investigation of Preprocessing and Validation Methodologies for PAT: Case study of the granulation and coating steps for the manufacturing of ethenzamide tablets

09 Jun 2023 | Contributor(s): Shibayama, Shojiro, Funatsu, Kimito

After the Food and Drug Association in the USA published guidelines on the enhanced use of process analytical technology (PAT) and continuous manufacturing, many studies regarding PAT and continuous manufacturing have been published. This paper describes a case study involving granulation and...

Investigation of the effect of impeller rotation rate, powder flow rate, and cohesion on powder flow behavior in a continuous blender using PEPT

09 Jun 2023 | Contributor(s): Portillo, PM, Vanarase, AU, Ingram, A, Seville, JK, Ierapetritou, MG, Muzzio, FJ

In this paper, we examine the movement of particles within a continuous powder mixer using PEPT (Positron Emission Particle Tracking). The benefit of the approach is that the particle movement along the vessel can be measured non-invasively. The effect of impeller rotation rate, powder flow rate,...

Investigation of the variability of NIR in-line monitoring of roller compaction process by using Fast Fourier Transform (FFT) analysis

09 Jun 2023 | Contributor(s): Feng, Tao, Wang, Feng, Pinal, Rodolfo, Wassgren, Carl, Carvajal, M. Teresa

The purpose of this Research Article was to investigate the variability of the roller compaction process while monitoring in-line with near-infrared (NIR) spectroscopy. In this paper, a pragmatic method in determining this variability of in-line NIR monitoring roller compaction process was...

Investigation of Wet Milling and Indirect Ultrasound as Means for Controlling Nucleation in the Continuous Crystallization of an Active Pharmaceutical Ingredient

09 Jun 2023 | Contributor(s): Yang, YH, Ahmed, BMitchell, C, Quon, JL, Siddique, H, Houson, I, Florence, AJ, Papageorgiou, CD

This study compares the use of wet milling and indirect ultrasound for promoting nucleation and controlling the particle size during the continuous crystallization of a hard-to-nucleate active pharmaceutical ingredient (API). Both an immersion and an external wet mill installed on a recirculation...

Ionic liquids for energy, materials, and medicine

09 Jun 2023 | Contributor(s): Smiglak, M, Pringle, JMLu, X, Han, L, Zhang, S, Gao, H, MacFarlane, DR, Rogers, RD

As highlighted by the recent ChemComm web themed issue on ionic liquids, this field continues to develop beyond the concept of interesting new solvents for application in the greening of the chemical industry. Here some current Research Article trends in the field will be discussed which show...

Ionic liquids in pharmaceutical industry: A systematic review on applications and future perspectives

09 Jun 2023 | Contributor(s): Zhuang, WC, Hachem, KBokov, D, Ansari, MJ, Nakhjiri, AT

Ionic liquids (ILs) have demonstrated incredible potential of application in various industries such as pharmaceutics. Appropriate utilization of ILs in the pharmaceutical industry can be a great option to overcome the operational/functional challenges related to the use of traditional organic...

Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions

09 Jun 2023 | Contributor(s): Cole, Kevin, Groh, Jennifer McClary, Johnson, Martin D., Burcham, Christopher L., Campbell, Bradley M., Diseroad, William D., Heller, Michael R., Howell, John R., Kallman, Neil J., Koenig, Thomas M., May, Scott A., Miller, Richard D., Mitchell, David, Myers, David P., Myers, Steven S., Phillips, Joseph L., Polster, Christopher S., White, Timothy D., Cashman, Jim, Hurley, Declan, Moylan, Robert, Sheehan, Paul, Spencer, Richard D., Desmond, Kenneth, Desmond, Paul., Gowran, Olivia

Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process...

Kinetic identification and experimental validation of continuous plug flow crystallisation

09 Jun 2023 | Contributor(s): Zhao, Yan, Kamaraju, Vamsi Krishna Hou, Guangyang Power, Graham, Donnellan, Philip, Glennon, Brian

This paper investigates the suitability of a number of potential crystallisation models to best describe the experimentally observed behaviour of the antisolvent crystallisation of benzoic acid from aqueous ethanol solution using water as an antisolvent, in a continuous plug flow crystalliser....

Laboratory of the future: a modular flow platform with multiple integrated PAT tools for multistep reactions

09 Jun 2023 | Contributor(s): Sagmeister, Peter, Hone, Christopher, Williams, Jason D, Kappe, Oliver

Currently, the monitoring of multistep continuous flow processes by multiple analytical sources is still seen as a resource intensive and specialized activity. In this article, the coupling of a modular microreactor platform with real-time monitoring by inline IR and NMR, in addition to online...

Landscape and opportunities for active pharmaceutical ingredient manufacturing in developing African economies

09 Jun 2023 | Contributor(s): Riley, DL, Strydom, IChikwamba, R, Panayides, JL

Africa is one of the world's fastest growing economies, with South Africa having the fifth highest worldwide pharmaceutical expenditure per capita. In recent years, several companies have considered regional pharmaceutical production but have failed to make the investment, in stark contrast to...

Integrated continuous manufacturing in pharmaceutical industry: current eolutionary steps toward revolutionary future

09 Jun 2023 | Contributor(s): Nada A Helal, Ola Elnoweam, Heba Abdullah Eassa, Ahmed M Amer, Mohamed Ashraf Eltokhy, Mohamed A Helal, Heba A Fayyaz, Mohamed Ismail Nonou

Continuous manufacturing (CM) has the potential to provide pharmaceutical products with better quality, improved yield and with reduced cost and time. Moreover, ease of scale-up, small manufacturing footprint and on-line/in-line monitoring and control of the process are other merits for CM....

Integrated design and control for robust performance: Application to an MSMPR crystallizer

09 Jun 2023 | Contributor(s): Grosch, R., Mönnigmann, M., Marquardt, W.

The interplay of different types of performance constraints in an integrated design and control problem is studied by means of a case study. This integrated problem is based on a recent method for robust process design [M. Mönnigmann, W. Marquardt, Normal vectors on manifolds of critical points...

Integrated Flow Processing - Challenges in Continuous Multistep Synthesis

09 Jun 2023 | Contributor(s): Pieber, B, Gilmore, K, Seeberger, PH

The way organic multistep synthesis is performed is changing due to the adoption of flow chemical techniques, which has enabled the development of improved methods to make complex molecules. The modular nature of the technique provides not only access to target molecules via linear flow...

Integrated hot-melt extrusion - injection molding continuous tablet manufacturing platform: Effects of critical process parameters and formulation attributes on product robustness and dimensional stability

09 Jun 2023 | Contributor(s): Desai, Parind M, Hogan, Rachael C., Brancazio, David, Puri, Vibha, Jensen, Keith D., Chun, Jung-Hoon, Myerson, Allan S., Trout, Bernhardt L.

This study provides a framework for robust tablet development using an integrated hot-melt extrusion-injection molding (IM) continuous manufacturing platform. Griseofulvin, maltodextrin, xylitol and lactose were employed as drug, carrier, plasticizer and reinforcing agent respectively. A...

Integrated moving horizon-based dynamic real-time optimization and hybrid MPC-PID control of a direct compaction continuous tablet manufacturing process

09 Jun 2023 | Contributor(s): Singh, Ravendra, Sen, Maitraye Ierapetritou, Marianthi, Ramachandran, Rohit

In this manuscript, a moving horizon-based real-time optimization (MH-RTO) has been integrated with a hybrid model predictive control (MPC) system for a continuous tablet manufacturing process for quality by design (QbD)-based efficient continuous manufacturing. In the proposed approach, the...

Integrated Purification and Formulation of an Active Pharmaceutical Ingredient via Agitated Bed Crystallization and Fluidized Bed Processing

09 Jun 2023 | Contributor(s): Stocker, MW, Harding, MJTodaro, V, Healy, AM, Ferguson, S

Integrated API and drug product processing enable molecules with high clinical efficacy but poor physicochemical characteristics to be commercialized by direct co-processing with excipients to produce advanced multicomponent intermediates. Furthermore, developing isolation-free frameworks would...

Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line

09 Jun 2023 | Contributor(s): Fulop, G., Domokos, A., Galata, D., Szabo, E., Gyurkes, M., Szabo, B., Farkas, A., Madarasz, L., Demuth, B., Lender, T., Nagy, T., Kovacs-Kiss, D., Van der Gucht, f, Marosi, G., Nagy, Z. K.

Highly homogeneous low-dose (50 mu g) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a...

Integrating sensors for monitoring blend content in a pharmaceutical continuous manufacturing plant

09 Jun 2023 | Contributor(s): Panikar, Savitha, Li, Jingzhe, Rane, Varsha, Gillam, Sean, Callegari, Gerardo, Kurtyka, Bogdan, Lee, Sau, Muzzio, Fernando

In a pharmaceutical manufacturing process, Critical Quality Attributes (CQAs) need to be monitored not only for the final product but also for intermediates. Blend uniformity of powders is one such attribute that needs to be measured to ensure the quality of the final product. Multiple in-line...

Intelligent Alarm Management Applied to Continuous Pharmaceutical Tablet Manufacturing: An Integrated Approach

09 Jun 2023 | Contributor(s): Gupta, Anshu, Giridhar, Arun, Venkatasubramanian, Venkat., Reklaitis, Gintaras V.

One important aspect of effective real time process management is the implementation of intelligent systems that can assist human operators in making supervisory control decisions. Conventional practice is to simply sound alarms when process variables go out of range leaving it to the operator to...

Intermolecular hydrogen transfer and solubility tuning in multi-component molecular crystals of the API piroxicam

09 Jun 2023 | Contributor(s): Thomas, LH, Klapwijk, ARWales, C, Wilson, CC

A series of twelve multi-component molecular crystals of the active pharmaceutical ingredient (API) piroxicam (PX) have been synthesised and their structures analysed with respect to their supramolecular motifs and degree of intermolecular hydrogen transfer observed on formation of the various...

Inline monitoring and a PAT strategy for pharmaceutical hot-melt extrusion

09 Jun 2023 | Contributor(s): Wahl, PR, Treffer, DMohr, S, Roblegg, E, Koscher, G, Khinast, JG

Implementation of continuous manufacturing in the pharmaceutical industry requires tight process control. This study focuses on a PAT strategy for hot melt extrusion of vegetable calcium stearate (CaSt) as matrix carrier and paracetamol as active pharmaceutical ingredient (API). The extrusion was...

In-line monitoring and optimization of powder flow in a simulated continuous process using transmission near infrared spectroscopy

09 Jun 2023 | Contributor(s): Alam, Md Anik, Shi, Zhenqi, Drennen, James K, Anderson, Carl A

In-line monitoring of continuous powder flow is an integral part of the continuous manufacturing process of solid oral dosage forms in the pharmaceutical industry. Specifically, monitoring downstream from loss-in-weight (LIW) feeders and/or continuous mixers provides important data about the...

In-line monitoring of granule moisture in fluidized-bed dryers using microwave resonance technology

09 Jun 2023 | Contributor(s): Buschmueller, Caroline, Wiedey, Wolfgang, Doescher, Claas, Dressler, Jochen, Breitkreutz, Joerg

This is the first report on in-line moisture measurement of pharmaceutical products by microwave resonance technology. In order to meet the FDA's PAT approach, a microwave resonance sensor appropriate for pharmaceutical use was developed and implemented into two different fluidized-bed dryers....