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...

Application of a System Model for Continuous Manufacturing of an Active Pharmaceutical Ingredient in an Industrial Environment

09 Jun 2023 | Contributor(s): Diab, S, Bano, GChristodoulou, C, Hodnett, N, Benedetti, A, Andersson, M, Zomer, S

Purpose In pharmaceutical manufacturing, understanding and quantifying how process conditions impact product quality is pivotal to guaranteeing process profitability with sustained product yield. We describe an integrated system model for a commercial-scale continuous manufacturing process of a...

Application of Continuous Crystallization in an Integrated Continuous Pharmaceutical Pilot Plant

09 Jun 2023 | Contributor(s): Zhang, Haitao, Lakerveld, Richard, Heider, Patrick, Tao, Mengying, Su, Min, Testa, Christopher, D’Antonio, Alyssa, Barton, Paul, Braatz, Richard, Trout, Bernhardt, Myerson, Allan, Jensen, Klavs, Evans, James

Real-time control using process analytical technology (PAT) tools is required for the implementation of continuous crystallization within integrated continuous manufacturing (ICM) of pharmaceuticals. However, appropriate selection of PAT tools is challenging, and the design and operation of...

Application of continuous twin screw granulation for the metformin hydrochloride extended release formulation

09 Jun 2023 | Contributor(s): Kim, Su-Hyeon, Hwang, Kyu-Min, Cho, Cheol-Hee, Nguyen, Thi-Tram, Seok, Su Hyun, Hwang, Kyu-Mok, Kim, Ju-Young, Park, Chun-Woong, Rhee, Yun-Seok, Park, Eun-Seok

This study focuses on evaluating the potential of transferring from a batch process to continuous process for manufacturing of the extended release formulation. Metformin hydrochloride (HCl) was used in the model formulation which was intended to contain the high amount of hydrophilic drug. The...

Application of FT-NIR Analysis for In-line and Real-Time Monitoring of Pharmaceutical Hot Melt Extrusion: a Technical Note

09 Jun 2023 | Contributor(s): Vo, Anh Q., He, Herman, Zhang, Jiaxiang, Martin, Scott, Chen, Rui, Repka, Michael A.

Continuous manufacturing, a gaining interest paradigm in the pharmaceutical industry, requires in-process monitoring of critical process parameters to ensure product consistency. This study demonstrated the application of Fourier transform near-infrared (FT-NIR) spectroscopy in conjunction with...

Application of mechanistic models within a PAT framework

09 Jun 2023 | Contributor(s): Gernaey, Krist, Sin, Gürkan Albo, E Woodley, John Singh, Ravendra, Gani, Rafiqul

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Application of Model-Free and Model-Based Quality-by-Control (QbC) for the Efficient Design of Pharmaceutical Crystallization Processes

09 Jun 2023 | Contributor(s): Szilagyi, Botond, Eren, Ayse Quon, Justin L. Papageorgiou, Charles D., Nagy, Zoltan K.

The design of pharmaceutical crystallization processes is a challenging engineering problem because of the specific and versatile quality requirements of the end-product, amplified by the tight regulatory standards. The current industrial standard for crystallization process design is based on...

Application of multivariate methods to compression behavior evaluation of directly compressible materials

09 Jun 2023 | Contributor(s): Haware, Rahul V., Tho, Ingunn, Bauer-Brandl, Annette

The present study is an approach to describe and predict compaction and tablet properties by a combination of a set of commonly used mathematical descriptors and multivariate methods based on continuous compression profiles. Effects of formulation and process parameters (e.g. composition, powder...

An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles

09 Jun 2023 | Contributor(s): Lorenz, T, Bojko, SBunjes, H, Dietzel, A

Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification...

An Innovative Sampling Interface for Monitoring Flowing Pharmaceutical Powder Mixtures

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

A chute was designed following the principles of the Theory of Sampling to minimize the variations in powder flow and provide all particles in the flowing blends with the same opportunity of being selected as a sample. The design also reduces the thickness of the chute to allow the analysis of a...

An Integrated Continuous Flow Micro-Total Ultrafast Process System (mu-TUFPS) for the Synthesis of Celecoxib and Other Cyclooxygenase Inhibitors

09 Jun 2023 | Contributor(s): Sthalam, VK, Singh, AK, Pabbaraja, S

Integrated continuous manufacturing has emerged as a promising device for the rapid manufacturing of active pharmaceutical ingredients (APIs). We herein report a newly designed continuous flow micro-total process system platform for the rapid manufacturing of celecoxib, a selective nonsteroidal...

An ontological knowledge-based system for the selection of process monitoring and analysis tools

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

Efficient process monitoring and analysis tools provide the means for automated supervision and control of manufacturing plants and therefore play an important role in plant safety, process control and assurance of end product quality. The availability of a large number of different process...

An Overview of Pharmaceutical Manufacturing for Solid Dosage Forms

09 Jun 2023 | Contributor(s): Sacher, Stephan, Khinast, Johannes G.

In this chapter, the main processing steps and manufacturing aspects of solid dosage forms are described and the relevant literature is reviewed. Starting with powder feeding, powder blending, granulation (dry and wet), and drying the most important unit operations to make compactable granules...

Analysing drying unit performance in a continuous pharmaceutical manufacturing line by means of mass - Energy balances

09 Jun 2023 | Contributor(s): Mortier, Severine Therese F. C., Gernaey, Krist V., De Beer, Thomas, Nopens, Ingmar

The current trend in the pharmaceutical industry to move from batch-wise to continuous production processes strengthens the need for monitoring and controlling the process in-line. The ConsiGma(Tm) continuous tableting line collects data of the different subunits in real-time, but these are not...

Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy

09 Jun 2023 | Contributor(s): Mateo-Ortiz Daniel, Colon, Yleana, Romañach, Rodolfo, Mendez, Rafael

New analytical methods are needed to understand and optimize the processes by which tablets are produced. Fette 3090 tablet presses are commonly used in the pharmaceutical industry. A near-infrared (NIR) probe was installed into a Fette 3090 feed frame to understand and monitor the die filling...

Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation

09 Jun 2023 | Contributor(s): Matsunami, Kensaku, Ryckaert, Alexander, Peeters, Michiel, Badr, Sara, Sugiyama, Hirokazu, Nopens, Ingmar, De Beer, Thomas

Toward further implementation of continuous tablet manufacturing, one key issue is the time needed for start-up operation because it could lead to lower product yield and reduced economic performance. The behavior of the start-up operation is not well understood; moreover, the definition of the...

Analytical Design and Operation of Systems with Crystallization, Filtration, and Recycling

09 Jun 2023 | Contributor(s): Ward, Jeffrey D, Yu, Cheng-ching, Doherty, Michael F

In this article, we introduce an analogous dimensionless model for a continuous rotary drum filter and show that a similar methodology can be used to predict the behavior of a combined crystallizer and filter, and a reactor, crystallizer, filter, and recycle circuit. We show the effect of the...

Analytical Method Quality by Design for an On-Line Near-Infrared Method to Monitor Blend Potency and Uniformity

09 Jun 2023 | Contributor(s): Corredor, Claudia, Bu, Xin, McCann, Ryan, Dougherty, Jeffrey, Stevens, Tim, Both, Douglas, Shah, Pankaj

In this work, an example of analytical method quality by design (AQbD) principles applied to an in-line NIR method to monitor blend potency and uniformity in the manufacturing of an oral solid dosage product is presented. An integrated process analytical technology (PAT) method was developed...

Analytical Procedure Development

09 Jun 2023

Guideline provides a foundation for consistent development of analytical methods to maintain precision and accuracy, contirubting to the maintenance of quality products.

Analytical Validation

09 Jun 2023

Guideline establishes the requirements for validationg analytical methods, ensuring consistency in the routeine measurements of pharmaceutical products and their intermediates.

Advanced methodologies for cocrystal synthesis

09 Jun 2023 | Contributor(s): Douroumis, D, Ross, SA, Nokhodchi, A

Pharmaceutical cocrystals are multicomponent systems composed of two or more molecules and held together by H-bonding. Currently, cocrystals provide exciting opportunities in the pharmaceutical industry for the development and manufacturing of new medicines by improving poor physical properties...

Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press

09 Jun 2023 | Contributor(s): Haas, Nicholas Townsend, Ierapetritou, Marianthi, Singh, Ravendra

In continuous pharmaceutical manufacturing, real-time precise control of critical quality attributes (CQAs) is necessary for quality by design (QbD)-based manufacturing and real-time release (RTR) with minimum consumption of time, space, and resources. Pharmaceutical tablets can be produced...

Advanced Pharmaceutical Manufacturing: A Functional Definition

09 Jun 2023 | Contributor(s): Romañach, Rodolfo J., Stelzer, Torsten, Sanchez, Eric, Muzzio, Fernando

The term “Advanced Pharmaceutical Manufacturing” (APM) has become an ubiquitous buzzword with deep potential policy implications. There is a real danger that APM will be seen as a general panacea for solving economic woes and drug shortages, devoiding it from specific meaning, and depriving the...

Advanced Real-Time Process Analytics for Multistep Synthesis in Continuous Flow

09 Jun 2023 | Contributor(s): Sagmeister, Peter, Lebl, René, Castillo, Ismael, Rehrl, Jakob, Kruisz, Julia, Sipek, Martin, Horn, Martin, Sacher, Stephan, Cantillo, David, Williams, Jason D, Kappe, Oliver

In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and...

Advances in Continuous Active Pharmaceutical Ingredient (API) Manufacturing: Real-time Monitoring Using Multivariate Tools

09 Jun 2023 | Contributor(s): Dumarey, Melanie, Hermanto, Martin, Airiau, Christian, Shapland, Peter, Robinson, Hannah, Hamilton, Peter, Berry, Malcom

Purpose: The implementation of continuous processing technologies for pharmaceutical manufacturing has increased due to its potential to enhance supply chain flexibility, reduce the footprint of the manufacturing facility, and deliver more consistent quality. Additionally, it facilitates...