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)...

Effect of batch-to-batch variation of spray dried lactose on the performance of feeders

10 Aug 2023 | Peer-reviewed journal | Contributor(s): Carlota Mendez Torrecillas, Florian Tegel, Ralf Weinekötter, Bernhard Meir, Bastiaan H.J. Dickhoff, Sri Sharath Kulkarni, Pauline H.M. Janssen

With the emergence of quality by design (QbD), it becomes imperative to gain understanding of the impact of batch-to-batch variability of raw materials on the performance of processes. Feeding is the first unit of operation in a continuous manufacturing line and is critical for the final product...

Impact of material properties and process parameters on tablet quality in a continuous direct compression line

09 Aug 2023 | Peer-reviewed journal | Contributor(s): Pauline H.M. Janssen, Sara Fathollahi Bram Bekaert, Dirk Vanderroost, Timo Roelofs, Valerie Vanhoorne, Chris Vervaet, Bastiaan H.J. Dickhoff

The current paper shows how excipient properties impact the process parameters and the final tablet properties in a fully integrated continuous direct compression line. Blend properties of low-dose (1% w/w) and high-dose (40% w/w) paracetamol formulations were evaluated...

Process intensification using a semi-continuous mini-blender to support continuous direct compression processing

04 Aug 2023 | Peer-reviewed journal | Contributor(s): Alexandra Lohrmann, Florian Tegel, Muhammad Khalid Maqsood, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff, Maarten Jaspers, Timo P. Roelofs

The production of pharmaceutical tablets is shifting towards continuous manufacturing. Therefore, individual unit operations such as powder blending need to be re-designed. Continuous powder blending has been implemented successfully, but for low-dose formulations this is challenging due to...

Model predictive in vitro dissolution testing in pharmaceutical continuous manufacturing: An equivalence study

12 Jul 2023 | Peer-reviewed journal | Contributor(s): Atul Dubey, Su Qinglin, Paul Hermant, Federica Casati, Bhakti Halkude, Wei Wu, Anjana Ramnath, Stephen Born, Salvatore Mascia, Bayan Takizawa

A predictive mathematical model for tablet dissolution was developed and implemented in an end-to-end integrated continuous manufacturing pilot plant. The tablets were produced for immediate release with a proprietary extrusion-molding-coating (EMC) unit operation. Besides the mass balance of...

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...

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...

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...

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...