Control strategy definition for a drug product continuous wet granulation process: Industrial case study

09 Jun 2023 | Contributor(s): Chavez, Pierre-François, Stauffer, Fanny, Eeckman, Frédéric, Bostijn, Nils, Didion, David, Schaefer, Cédric, Yang, Hong, El Aalamat, Yousef, Lories, Xavier, Warman, Martin, Mathieu, Benoit, Mantanus, Jérôme

This paper describes the specific control strategy of the commercial manufacturing process of an immediate release tablet formulation based on continuous twin-screw wet granulation. This control strategy has been defined by a multidisciplinary team using an enhanced approach, in alignment with...

Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century

09 Jun 2023 | Contributor(s): Tiwari, RV, Patil, H, Repka, MA

Introduction: Hot-melt extrusion (HME) technology is applied successfully in the plastic, rubber and food industry. HME has also emerged as an important technology for drug delivery applications in pharmaceutical Research Article and manufacturing because of its process automation and low-cost...

Control of Batch and Continuous Crystallization Processes using Reinforcement Learning

09 Jun 2023 | Contributor(s): Benyahia, Brahim, Anandan, Paul Danny Rielly, Chris Türkay, Metin, Gani, Rafiqul

In crystallization processes, the control of particle size distribution, shape and purity are crucial to achieve the targeted critical quality attributes of the final drug product and meet the pharmaceutical regulatory requirements. This work presents novel optimal trajectory tracking control...

Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous Research Article identified lactose/MCC/HPMC as a...

Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, Leys, Jan, Klingeleers, Didier, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite significant advances in the Research Article domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent...

Continuous twin screw granulation: Influence of process and formulation variables on granule quality attributes of model formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, Kenny, Delaet, Urbain, Vigh, Tamas, Kumar, Ashish, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, continuous manufacturing techniques, such as twin screw wet granulation, have gained significant momentum. Due to the large diversity of the (model) formulations and equipment, it is often difficult to generalize conclusions about the importance of process settings. As only...

Continuous twin screw granulation: Robustness of lactose/MCC-based formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, De Vriendt, Charlotte, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response...

Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, Leys, Jan, Klingeleers, Didier, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite significant advances in the Research Article domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent...

Continuous twin screw granulation: Influence of process and formulation variables on granule quality attributes of model formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, Kenny, Delaet, Urbain, Vigh, Tamas, Kumar, Ashish, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, continuous manufacturing techniques, such as twin screw wet granulation, have gained significant momentum. Due to the large diversity of the (model) formulations and equipment, it is often difficult to generalize conclusions about the importance of process settings. As only...

Continuous twin screw granulation: Influence of process variables on granule and tablet quality

09 Jun 2023 | Contributor(s): Vercruysse, J., Diaz, D. Cordoba, Peeters, E., Fonteyne, M., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Veryaet, C.

The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, alpha-lactose monohydrate...

Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous Research Article identified lactose/MCC/HPMC as a...

Continuous twin screw granulation: Robustness of lactose/MCC-based formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, De Vriendt, Charlotte, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response...

Continuous twin screw wet granulation: The combined effect of process parameters on residence time, particle size, and granule morphology

09 Jun 2023 | Contributor(s): Shirazian, Saeed, Zeglinski, Jacek, Darwish, Shaza, Kuhs, Manuel, Albadarin, Ahmad B., Croker, Denise M., Walker, Gavin M.

In this study, a set of 24 experiments was designed to understand the combined effect of different process parameters, i.e. material feed rate, liquid-to-solid (L/S) ratio, screw speed, and screw configuration on the residence time distribution, granule morphology, and particle size distribution...

Continuous, one-step synthesis of pharmaceutical cocrystals via hot melt extrusion from neat to matrix-assisted processing - State of the art

09 Jun 2023 | Contributor(s): Gajda, Maciej, Nartowski, Karol P., Pluta, Janusz, Karolewicz, Bożena

Use of hot melt extrusion (HME) as continuous manufacturing process in the cocrystal synthesis is of increasing interest from both industrial and academic perspective and it is seen as a newly developing branch of mechanochemistry with possible broad application in single step synthesis and...

Continuous-Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

09 Jun 2023 | Contributor(s): Gutmann, B, Cantillo, D, Kappe, CO

In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of...

Continuous-Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

09 Jun 2023 | Contributor(s): Gutmann, B, Cantillo, D, Kappe, CO

In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of...

Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous Research Article identified lactose/MCC/HPMC as a...

Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, Leys, Jan, Klingeleers, Didier, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite significant advances in the Research Article domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent...

Continuous twin screw granulation: Influence of process and formulation variables on granule quality attributes of model formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, Kenny, Delaet, Urbain, Vigh, Tamas, Kumar, Ashish, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, continuous manufacturing techniques, such as twin screw wet granulation, have gained significant momentum. Due to the large diversity of the (model) formulations and equipment, it is often difficult to generalize conclusions about the importance of process settings. As only...

Continuous twin screw granulation: Influence of process variables on granule and tablet quality

09 Jun 2023 | Contributor(s): Vercruysse, J., Diaz, D. Cordoba, Peeters, E., Fonteyne, M., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Veryaet, C.

The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, alpha-lactose monohydrate...

Continuous twin screw granulation: Robustness of lactose/MCC-based formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, De Vriendt, Charlotte, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response...

Continuous twin screw granulation - An advanced alternative granulation technology for use in the pharmaceutical industry

09 Jun 2023 | Contributor(s): Bandari, Suresh, Nyavanandi, Dinesh, Kallakunta, Venkata Raman, Janga, Kartik Yadav, Sarabu, Sandeep, Butreddy, Arun, Repka, Michael A.

Hot melt extrusion has been an exciting technology in the pharmaceutical field owing to its novel applicability. Twin-screw granulation presents a great potential and offers many advantages relative to conventional granulation processes. Different twin-screw granulation techniques, such as...

Continuous twin screw granulation and fluid bed drying: A mechanistic scaling approach focusing optimal tablet properties

09 Jun 2023 | Contributor(s): Menth, Judith, Maus, Martin, Wagner, Karl G.

This study provides the results of investigation on scaling approaches for three differently-sized continuous granulation lines, each consisting of a twin screw wet granulation process and a continuous fluid bed drying process. To check the initial scaling approach with regard to granule and...

Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, KDelaet, U, Vigh, T, Di, Pretoro, G, De, Beer, T, Vervaet, C, Vanhoorne, V

Due to the numerous advantages over batch manufacturing, continuous manufacturing techniques such as twin screw wet granulation are rapidly gaining importance in pharmaceutical production. Since a large knowledge gap on the importance of formulation variables exists, this study systematically...

Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design

09 Jun 2023 | Contributor(s): Portier, Christoph, Vervaet, Chris, Vanhoorne, Valérie

Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in...