Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 1. Calibration workflow

24 Oct 2024 | Peer-reviewed journal | Contributor(s): Peter Toson, Marko Matić, Theresa Hörmann-Kincses, Michela Beretta, Jakob Rehrl, Johannes Poms, Thomas O’Connor, Abdollah Koolivand, Geng Tian, Scott M. Krull, Johannes G. Khinast, Dalibor Jajcevic, Johan Remmelgas

In this work, a high-fidelity digital twin was developed to support the design and testing of control strategies for drug product manufacturing via direct compression. The high-fidelity digital twin platform was based on typical pharmaceutical equipment, materials, and direct compression...

Continuous Processing. Continuous Evolution

08 Oct 2024 | Magazine | Contributor(s): Douglas Hausner

Continuous processing for small molecule products has been a hot topic for years, but where does the industry stand with it today? We speak with Doug Hausner, Senior Manager, Continuous Manufacturing, Oral Solid Dose, Pharma Services at Thermo Fisher Scientific, to find out.

Continuous micro feeding and mixing of solid dosage forms under vibrational excitation

08 Oct 2024 | Peer-reviewed journal | Contributor(s): Haifeng Lu, Liang Zhang, Hui Du, Xiaolei Guo, Haifeng Liu

Continuous manufacturing has intrigued many researchers in the pharmaceutical industry in the post-COVID-19 world. We experimentally studied the discharge characteristics of pharmaceutical excipients under vibrational excitation. The successful accurate dosing and filling of powders at fill...

Systematic investigation of the impact of screw elements in continuous wet granulation

10 Sep 2024 | Peer-reviewed journal | Contributor(s): Katharina Kiricenko, Peter Kleinebudde, Robin Meier

Twin-screw wet granulation (TSG) is a continuous manufacturing technique either for granules as final dosage form or as an intermediate before tableting or capsule filling. A comprehensive process understanding is required to implement TSG, considering various parameters influencing granule and...

The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration

23 Jul 2024 | Peer-reviewed journal | Contributor(s): Movilla-Meza, Nathaly A., Sierra-Vega, Nobel O., Alvarado-Hernández, Bárbara B., Méndez, Rafael, Romañach, Rodolfo J.

Purpose: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Methods: Calibration models...

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients

23 Jul 2024 | Peer-reviewed journal | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...

Process analytics for the new era of continuous RNA manufacturing

23 Jul 2024 | Website | Contributor(s): Botonjic-Sehic, Edita

In this article, Edita Botonjic-Sehic, Head of Process Analytics and Data Science at ReciBioPharm, examines the need for a digitally controlled continuous manufacturing process to correct the shortcomings of the current standard of batch processing. She highlights the critical role in-line...

Improvement of a pharmaceutical powder mixing process in a tote blender via DEM simulations

04 Jun 2024 | Peer-reviewed journal | Contributor(s): Benedict Benque, Luca Orefice, Thomas Forgber, Matthias Habeler, Beate Schmid, Johan Remmelgas, Johannes Khinast

An industrial-scale pharmaceutical powder blending process was studied via discrete element method (DEM) simulations. A DEM model of two active pharmaceutical ingredient (API) components and a combined excipient component was calibrated by matching the simulated response in a dynamic angle of...

A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction

03 Jun 2024 | Peer-reviewed journal | Contributor(s): Hikaru G. Jolliffe, Martin Prostredny, Carlota Mendez Torrecillas, Ecaterina Bordos, Collette Tierney, Ebenezer Ojo, Richard Elkes, Gavin Reynolds, Yunfei Li Song, Bernhard Meir, Sara Fathollahi, John Robertson

Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body...

Influence of refilling on dosing accuracy of loss-in-weight powder feeders in continuous manufacturing

19 Feb 2024 | Peer-reviewed journal | Contributor(s): Jochen Thies, Peter Kleinebudde, Fabiola N. Santamaría Alvarez

Continuous manufacturing is a novel concept to produce high quality drug products. The manufacture of solid dosage forms starts with the feeding of materials, which is consider a critical step because it could have a high influence on the quality of the final product. Therefore, this unit...

MOOC I Blending - Flow and Mixing Regime

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Feeding - Refill Strategy

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Blending Basics

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Continuous Blender Types

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Feeding - Twin Screw Feeder

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Feeding - Disturbances

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

MOOC I Continuous Blend Analysis

29 Nov 2023 | Teaching Materials | Contributor(s): RCPE

Pharmaceutical Continuous Manufacturing: A Guide to Control Strategies for Solid Oral Dose Drugs

23 Aug 2023 | Technical Guides | Contributor(s): Atul Dubey

Advanced manufacturing technologies like pharmaceutical continuous manufacturing (PCM) can provide potential efficiencies for many medicines and their ingredients, thereby facilitating geographic diversity in manufacturing and supply chain resilience. One of the ways the U.S. Pharmacopeia (USP)...

Videometric mass flow control: A new method for real-time measurement and feedback control of powder micro-feeding based on image analysis

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Madarasz, L, Kote, AGyurkes, M, Farkas, A, Hambalko, B, Pataki, H, Fulop, G, Marosi, G, Lengyel, L, Casian, T, Csorba, K, Nagy, ZK

The present paper reports the first monitoring and control of ultra-low dose powder feeding using a camera image-based mass flow measurement system. Caffeine was fed via a single-screw microfeeder as a model active pharmaceutical ingredient (API). The mass, mass flow and sizes of the particles...

Wet Granulation in a Twin-Screw Extruder: Implications of Screw Design

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Thompson, M. R., Sun, J.

Wet granulation in twin-screw extrusion machinery is an attractive technology for the continuous processing of pharmaceuticals. The performance of this machinery is integrally tied to its screw design yet little fundamental knowledge exists in this emerging field for granulation to intelligently...

WHAT are sampling errors-and WHAT can we do about them? Part 1

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Romañach, Rodolfo J., Joubert Castro, Aidalu, Esbensen, Kim H

The objective of this column is to provide easy-to-understand examples of sampling errors. Prompted by recent participationsand presentations at on-line conferences and meetings, we believe there is a need for a more fulfilling introduction andexemplification of the concept and real-world...

Variographic analysis: A new methodology for quality assurance of pharmaceutical blending processes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sánchez-Paternina, Adriluz, Sierra-Vega, Nobel O., Cárdenas, Vanessa, Méndez, Rafael, Esbensen, Kim H., Romañach, Rodolfo J.

Analytical methods for real time monitoring of pharmaceutical blending processes are thoroughly validated but not the sampling methods. Variographic analysis was investigated as a method to determine the sampling and analytical errors when the drug concentration of pharmaceutical powder blends is...

Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vercruysse, Jurgen, Toiviainen, Maunu, Fonteyne, Margot, Helkimo, Niko, Ketolainen, Jarkko, Juuti, Mikko, Delaet, Urbain, Van Assche, Ivo, Remon, Jean Paul, Vervaet, Chris, De Beer, Thomas

Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw...

Using a material property library to find surrogate materials for pharmaceutical process development

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Escotet-Espinoza, MS, Moghtadernejad, SScicolone, J, Wang, YF, Pereira, G, Schafer, E, Vigh, T, Klingeleers, D, Ierapetritou, M, Muzzio, FJ

Material properties are known to have a significant impact on pharmaceutical manufacturing performance, particularly for solid product processes. Evaluating the performance of a specific material, for example an active pharmaceutical ingredient or excipient, is critical during development stages...

Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bhalode, Pooja, Tian, Huayu Gupta, Shashwat Razavi, Sonia M Roman-Ospino, Andres Talebian, Shahrzad Singh, Ravendra Scicolone, James V Muzzio, Fernando J, Ierapetritou, Marianthi

While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA’s support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber,...